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Brad; Sheth, Prameet M.; Kaul, Rupert; Betts, Michael R.; Wong, David; Kovacs, Colin; Loutfy, Mona; Common, Andrew; Halpenny, Roberta; Ostrowski, Mario A. title: HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date: 2008-10-20 journal: PLoS One DOI: 10.1371/journal.pone.0003454 sha: doc_id: 8 cord_uid: 3dgjv0x1 file: cache/cord-003407-f5v3hhr8.json key: cord-003407-f5v3hhr8 authors: Hung, Ting-Chun; Jassey, Alagie; Lin, Chien-Ju; Liu, Ching-Hsuan; Lin, Chun-Ching; Yen, Ming-Hong; Lin, Liang-Tzung title: Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date: 2018-11-27 journal: Viruses DOI: 10.3390/v10120669 sha: doc_id: 3407 cord_uid: f5v3hhr8 file: cache/cord-000638-ss1435el.json key: cord-000638-ss1435el authors: Beq, Stephanie; Rozlan, Sandra; Pelletier, Sandy; Willems, Bernard; Bruneau, Julie; Lelievre, Jean-Daniel; Levy, Yves; Shoukry, Naglaa H.; Cheynier, Rémi title: Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date: 2012-04-16 journal: PLoS One DOI: 10.1371/journal.pone.0034326 sha: doc_id: 638 cord_uid: ss1435el file: cache/cord-000174-mgj9zfft.json key: cord-000174-mgj9zfft authors: Slavenburg, Serena; Heijdra, Yvonne F.; Drenth, Joost P. H. title: Pneumonitis as A Consequence of (Peg)Interferon-Ribavirin Combination Therapy for Hepatitis C: a Review of the Literature date: 2009-04-28 journal: Dig Dis Sci DOI: 10.1007/s10620-009-0797-1 sha: doc_id: 174 cord_uid: mgj9zfft file: cache/cord-000833-m6abyuvx.json key: cord-000833-m6abyuvx authors: Sekiguchi, Satoshi; Kimura, Kiminori; Chiyo, Tomoko; Ohtsuki, Takahiro; Tobita, Yoshimi; Tokunaga, Yuko; Yasui, Fumihiko; Tsukiyama-Kohara, Kyoko; Wakita, Takaji; Tanaka, Toshiyuki; Miyasaka, Masayuki; Mizuno, Kyosuke; Hayashi, Yukiko; Hishima, Tsunekazu; Matsushima, Kouji; Kohara, Michinori title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date: 2012-12-17 journal: PLoS One DOI: 10.1371/journal.pone.0051656 sha: doc_id: 833 cord_uid: m6abyuvx file: cache/cord-001421-6t5puo6p.json key: cord-001421-6t5puo6p authors: Marfà, Santiago; Crespo, Gonzalo; Reichenbach, Vedrana; Forns, Xavier; Casals, Gregori; Morales-Ruiz, Manuel; Navasa, Miquel; Jiménez, Wladimiro title: Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date: 2014-10-02 journal: PLoS One DOI: 10.1371/journal.pone.0109254 sha: doc_id: 1421 cord_uid: 6t5puo6p file: cache/cord-000786-ofpcgxce.json key: cord-000786-ofpcgxce authors: Chua, Brendon Y.; Johnson, Douglas; Tan, Amabel; Earnest-Silveira, Linda; Sekiya, Toshiki; Chin, Ruth; Torresi, Joseph; Jackson, David C. title: Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses date: 2012-10-16 journal: PLoS One DOI: 10.1371/journal.pone.0047492 sha: doc_id: 786 cord_uid: ofpcgxce file: cache/cord-000830-jiy4cp4n.json key: cord-000830-jiy4cp4n authors: Cobo, Fernando title: Application of Molecular Diagnostic Techniques for Viral Testing date: 2012-11-30 journal: Open Virol J DOI: 10.2174/1874357901206010104 sha: doc_id: 830 cord_uid: jiy4cp4n file: cache/cord-000473-jpow6iw1.json key: cord-000473-jpow6iw1 authors: Astrovskaya, Irina; Tork, Bassam; Mangul, Serghei; Westbrooks, Kelly; Măndoiu, Ion; Balfe, Peter; Zelikovsky, Alex title: Inferring viral quasispecies spectra from 454 pyrosequencing reads date: 2011-07-28 journal: BMC Bioinformatics DOI: 10.1186/1471-2105-12-s6-s1 sha: doc_id: 473 cord_uid: jpow6iw1 file: cache/cord-001834-6xf4o3oy.json key: cord-001834-6xf4o3oy authors: Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection date: 2015-10-07 journal: Int J Mol Sci DOI: 10.3390/ijms161023683 sha: doc_id: 1834 cord_uid: 6xf4o3oy file: cache/cord-003158-mhlqnj52.json key: cord-003158-mhlqnj52 authors: Wang, Qi; Hagedorn, Curt; Liu, Shuanghu title: Adapted HCV JFH1 variant is capable of accommodating a large foreign gene insert and allows lower level HCV replication and viral production date: 2018-07-13 journal: Int J Biol Sci DOI: 10.7150/ijbs.27411 sha: doc_id: 3158 cord_uid: mhlqnj52 file: cache/cord-006061-z9r5htm9.json key: cord-006061-z9r5htm9 authors: Hu, Bo; Li, Shanshan; Zhang, Zhanfeng; Xie, Shenggao; Hu, Yuqian; Huang, Xianzhang; Zheng, Yi title: HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation date: 2016-06-17 journal: Tumour Biol DOI: 10.1007/s13277-016-5100-4 sha: doc_id: 6061 cord_uid: z9r5htm9 file: cache/cord-006436-61mgtbj4.json key: cord-006436-61mgtbj4 authors: Yoshiba, Makoto; Sekiyama, Kazuhiko; Iwamura, Yukari; Sugata, Famio title: Development of reliable artificial liver support (ALS)-plasma exchange in combination with hemodiafiltration using high-performance membranes date: 1993 journal: Dig Dis Sci DOI: 10.1007/bf01316501 sha: doc_id: 6436 cord_uid: 61mgtbj4 file: cache/cord-005617-bxbogskm.json key: cord-005617-bxbogskm authors: Conway, Anna; Fernàndez-López, Laura; Reyes-Urueña, Juliana; Casabona, Jordi title: Hepatitis C Screening in Community-Based Voluntary Counselling and Testing Services in Europe: An Observational Study from the COBATEST Network 2014–2018 date: 2019-11-20 journal: J Community Health DOI: 10.1007/s10900-019-00780-0 sha: doc_id: 5617 cord_uid: bxbogskm file: cache/cord-006129-5rog0s98.json key: cord-006129-5rog0s98 authors: Hemida, Maged Gomaa; Ye, Xin; Thair, Simone; Yang, Decheng title: Exploiting the Therapeutic Potential of MicroRNAs in Viral Diseases: Expectations and Limitations date: 2012-08-16 journal: Mol Diagn Ther DOI: 10.1007/bf03256383 sha: doc_id: 6129 cord_uid: 5rog0s98 file: cache/cord-007236-8hiymqyb.json key: cord-007236-8hiymqyb authors: Sun, Ji-Min; Kim, Seong-Jun; Kim, Geon-Woo; Rhee, Jin-Kyu; Kim, Nam Doo; Jung, Heeyong; Jeun, Jungae; Lee, Seung-Hoon; Han, Seung Hyun; Shin, Chul Soo; Oh, Jong-Won title: Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway date: 2011-11-09 journal: J Antimicrob Chemother DOI: 10.1093/jac/dkr432 sha: doc_id: 7236 cord_uid: 8hiymqyb file: cache/cord-001848-idmj2d7p.json key: cord-001848-idmj2d7p authors: Onabajo, Olusegun O.; Porter-Gill, Patricia; Paquin, Ashley; Rao, Nina; Liu, Luyang; Tang, Wei; Brand, Nathan; Prokunina-Olsson, Ludmila title: Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date: 2015-11-01 journal: J Interferon Cytokine Res DOI: 10.1089/jir.2014.0161 sha: doc_id: 1848 cord_uid: idmj2d7p file: cache/cord-003993-3bozjfv7.json key: cord-003993-3bozjfv7 authors: Cagliani, Rachele; Forni, Diego; Sironi, Manuela title: Mode and tempo of human hepatitis virus evolution date: 2019-10-25 journal: Comput Struct Biotechnol J DOI: 10.1016/j.csbj.2019.09.007 sha: doc_id: 3993 cord_uid: 3bozjfv7 file: cache/cord-002410-2zi5iv2t.json key: cord-002410-2zi5iv2t authors: Bruening, Janina; Weigel, Bettina; Gerold, Gisa title: The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy date: 2017-02-01 journal: J Immunol Res DOI: 10.1155/2017/7232361 sha: doc_id: 2410 cord_uid: 2zi5iv2t file: cache/cord-007305-pkjfnhro.json key: cord-007305-pkjfnhro authors: Iosub, Silvia; Gromisch, Donald S. title: Leukonychia Partialis in Kawasaki Disease date: 1984-10-17 journal: J Infect Dis DOI: 10.1093/infdis/150.4.617-a sha: doc_id: 7305 cord_uid: pkjfnhro file: cache/cord-009263-w8bmmgtj.json key: cord-009263-w8bmmgtj authors: Colpitts, Che C.; Tsai, Pei-Ling; Zeisel, Mirjam B. title: Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process date: 2020-03-18 journal: Int J Mol Sci DOI: 10.3390/ijms21062091 sha: doc_id: 9263 cord_uid: w8bmmgtj file: cache/cord-002369-shk4n8f6.json key: cord-002369-shk4n8f6 authors: Fahmy, Ahmed M.; 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H.; Sarhan, Moustafa; Abdel-Rahman, Mohamed A.; Quintero-Hernandez, Veronica; Aoki-Utsubo, Chie; Moustafa, Mohsen A.; Possani, Lourival D.; Hotta, Hak title: Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus date: 2019-07-06 journal: Int J Pept Res Ther DOI: 10.1007/s10989-019-09888-2 sha: doc_id: 11026 cord_uid: iapgkz0p file: cache/cord-026112-58sa5z03.json key: cord-026112-58sa5z03 authors: Dehghani-Dehej, Farzaneh; Hosseini, Zinat; Mortazkar, Poupak; Khanaliha, Khadijeh; Esghaei, Maryam; Fakhim, Atousa; Bokharaei-Salim, Farah title: Prevalence of HCV and/or HBV coinfection in Iranian HIV-infected patients date: 2020-04-24 journal: nan DOI: 10.2217/fvl-2019-0066 sha: doc_id: 26112 cord_uid: 58sa5z03 file: cache/cord-018785-tcr5xlf8.json key: cord-018785-tcr5xlf8 authors: Nambiar, Puja; Silibovsky, Randi; Belden, Katherine A. title: Infection in Kidney Transplantation date: 2018-06-27 journal: Contemporary Kidney Transplantation DOI: 10.1007/978-3-319-19617-6_22 sha: doc_id: 18785 cord_uid: tcr5xlf8 file: cache/cord-030361-0tepkjdl.json key: cord-030361-0tepkjdl authors: Mohammed Abdul, Mubeen Khan; 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Barocas, Joshua A; Wurcel, Alysse; Nijhawan, Ank; Thakarar, Kinna; Lynfield, Ruth; Hurley, Hermione; Snowden, Jessica; Thornton, Alice; del Rio, Carlos title: Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA’s Advocacy Agenda date: 2020-10-01 journal: J Infect Dis DOI: 10.1093/infdis/jiz673 sha: doc_id: 253768 cord_uid: y35m3vh1 file: cache/cord-261287-l4649du3.json key: cord-261287-l4649du3 authors: Puoti, Massimo; Zanini, Barbara; Quinzan, Gian Paolo; Ravasio, Laura; Paraninfo, Giuseppe; Santantonio, Teresa; Rollo, Adriano; Artioli, Stefania; Maggiolo, Franco; Zaltron, Serena; MASTER HIV/HCV Co-infection study group; Raise, Enzo; Mignani, Ermenegildo; Resta, Francesco; Verucchi, Gabriella; Pastore, Giuseppe; Suter, Fredy; Carosi, Giampiero title: A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients() date: 2004-05-06 journal: J Hepatol DOI: 10.1016/j.jhep.2004.04.016 sha: doc_id: 261287 cord_uid: l4649du3 file: cache/cord-255781-55zrmgxq.json key: cord-255781-55zrmgxq authors: Bergman, Scott J.; Ferguson, McKenzie C.; Santanello, Cathy title: Interferons as Therapeutic Agents for Infectious Diseases date: 2011-12-31 journal: Infectious Disease Clinics of North America DOI: 10.1016/j.idc.2011.07.008 sha: doc_id: 255781 cord_uid: 55zrmgxq file: cache/cord-284904-qw1ig2v4.json key: cord-284904-qw1ig2v4 authors: Mizui, Tomokazu; Yamashina, Shunhei; Tanida, Isei; Takei, Yoshiyuki; Ueno, Takashi; Sakamoto, Naoya; Ikejima, Kenichi; Kitamura, Tsuneo; Enomoto, Nobuyuki; Sakai, Tatsuo; Kominami, Eiki; Watanabe, Sumio title: Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy date: 2009-09-17 journal: J Gastroenterol DOI: 10.1007/s00535-009-0132-9 sha: doc_id: 284904 cord_uid: qw1ig2v4 file: cache/cord-264936-3posyr5n.json key: cord-264936-3posyr5n authors: Mohammadzadeh, Sara; Khabiri, Alireza; Roohvand, Farzin; Memarnejadian, Arash; Salmanian, Ali Hatef; Ajdary, Soheila; Ehsani, Parastoo title: Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications date: 2014-11-24 journal: Hepat Mon DOI: 10.5812/hepatmon.20524 sha: doc_id: 264936 cord_uid: 3posyr5n file: cache/cord-015941-4fz79wzf.json key: cord-015941-4fz79wzf authors: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2018-11-10 journal: Advanced Techniques in Diagnostic Microbiology DOI: 10.1007/978-3-319-95111-9_2 sha: doc_id: 15941 cord_uid: 4fz79wzf file: cache/cord-005138-u2lwgyyf.json key: cord-005138-u2lwgyyf authors: Kou, Yi-Hen; Chou, Shang-Min; Wang, Yi-Ming; Chang, Ya-Tzu; Huang, Shao-Yong; Jung, Mei-Ying; Huang, Yu-Hsu; Chen, Mei-Ru; Chang, Ming-Fu; Chang, Shin C. title: Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A date: 2006-08-23 journal: J Biomed Sci DOI: 10.1007/s11373-006-9104-8 sha: doc_id: 5138 cord_uid: u2lwgyyf file: cache/cord-017764-h1w9gbxk.json key: cord-017764-h1w9gbxk authors: Meanwell, Nicholas A.; Belema, Makonen title: The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex date: 2018-06-08 journal: HCV: The Journey from Discovery to a Cure DOI: 10.1007/7355_2018_47 sha: doc_id: 17764 cord_uid: h1w9gbxk file: cache/cord-253825-d9borky8.json key: cord-253825-d9borky8 authors: Blaising, Julie; Polyak, Stephen J.; Pécheur, Eve-Isabelle title: Arbidol as a broad-spectrum antiviral: An update date: 2014-04-24 journal: Antiviral Res DOI: 10.1016/j.antiviral.2014.04.006 sha: doc_id: 253825 cord_uid: d9borky8 file: cache/cord-017948-fqhl1qb4.json key: cord-017948-fqhl1qb4 authors: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2012-04-05 journal: Advanced Techniques in Diagnostic Microbiology DOI: 10.1007/978-1-4614-3970-7_28 sha: doc_id: 17948 cord_uid: fqhl1qb4 file: cache/cord-020010-q58x6xb0.json key: cord-020010-q58x6xb0 authors: nan title: 19th ICAR Abstracts: date: 2006-03-13 journal: Antiviral Res DOI: 10.1016/j.antiviral.2006.02.001 sha: doc_id: 20010 cord_uid: q58x6xb0 file: cache/cord-023017-k6edtg58.json key: cord-023017-k6edtg58 authors: nan title: AASLD Abstracts (pp. 282A–382A) date: 2006-02-10 journal: Hepatology DOI: 10.1002/hep.1840380505 sha: doc_id: 23017 cord_uid: k6edtg58 file: cache/cord-024003-698d15gk.json key: cord-024003-698d15gk authors: Loutfy, Samah A; Elberry, Mostafa H; Farroh, Khaled Yehia; Mohamed, Hossam Taha; Mohamed, Aya A; Mohamed, ElChaimaa B; Faraag, Ahmed Hassan Ibrahim; Mousa, Shaker A title: Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines date: 2020-04-22 journal: Int J Nanomedicine DOI: 10.2147/ijn.s241702 sha: doc_id: 24003 cord_uid: 698d15gk file: cache/cord-256036-gd53s4dv.json key: cord-256036-gd53s4dv authors: Sandmann, Lisa; Ploss, Alexander title: Barriers of hepatitis C virus interspecies transmission date: 2013-01-01 journal: Virology DOI: 10.1016/j.virol.2012.09.044 sha: doc_id: 256036 cord_uid: gd53s4dv file: cache/cord-265588-1tcaleeo.json key: cord-265588-1tcaleeo authors: Yousaf, Tahir; Rafique, Shazia; Wahid, Fazli; Rehman, Sidra; Nazir, Abdul; Rafique, Javeria; Aslam, Kashif; Shabir, Ghulam; Shah, Shahid Masood title: Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus date: 2018-03-20 journal: Microb Pathog DOI: 10.1016/j.micpath.2018.03.030 sha: doc_id: 265588 cord_uid: 1tcaleeo file: cache/cord-281389-sht0yx4a.json key: cord-281389-sht0yx4a authors: Tal, Michal Caspi; Torrez Dulgeroff, Laughing Bear; Myers, Lara; Cham, Lamin B.; Mayer-Barber, Katrin D.; Bohrer, Andrea C.; Castro, Ehydel; Yiu, Ying Ying; Lopez Angel, Cesar; Pham, Ed; Carmody, Aaron B.; Messer, Ronald J.; Gars, Eric; Kortmann, Jens; Markovic, Maxim; Hasenkrug, Michaela; Peterson, Karin E.; Winkler, Clayton W.; Woods, Tyson A.; Hansen, Paige; Galloway, Sarah; Wagh, Dhananjay; Fram, Benjamin J.; Nguyen, Thai; Corey, Daniel; Kalluru, Raja Sab; Banaei, Niaz; Rajadas, Jayakumar; Monack, Denise M.; Ahmed, Aijaz; Sahoo, Debashis; Davis, Mark M.; Glenn, Jeffrey S.; Adomati, Tom; Lang, Karl S.; Weissman, Irving L.; Hasenkrug, Kim J. title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date: 2020-06-23 journal: mBio DOI: 10.1128/mbio.01293-20 sha: doc_id: 281389 cord_uid: sht0yx4a file: cache/cord-023033-tgt69ir6.json key: cord-023033-tgt69ir6 authors: nan title: Poster Session (pp. 78A–178A) date: 2006-02-10 journal: Hepatology DOI: 10.1002/hep.1840380503 sha: doc_id: 23033 cord_uid: tgt69ir6 file: cache/cord-264326-teahway7.json key: cord-264326-teahway7 authors: Eleftheriou, Phaedra; 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McBride, David R.; Basilan, Richard; Roland, William E.; McCrary, David; Hoonmo, Koo title: Infectious Diseases date: 2020-06-22 journal: Textbook of Family Medicine DOI: 10.1016/b978-1-4377-1160-8.10016-8 sha: doc_id: 27860 cord_uid: s97hdhh6 file: cache/cord-259916-gr6v098c.json key: cord-259916-gr6v098c authors: Wang, Hongliang; Tai, Andrew W. title: Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication date: 2016-05-20 journal: Viruses DOI: 10.3390/v8050142 sha: doc_id: 259916 cord_uid: gr6v098c file: cache/cord-276364-zyw5aukk.json key: cord-276364-zyw5aukk authors: Wong, Ho Him; Sanyal, Sumana title: Manipulation of autophagy by (+) RNA viruses date: 2019-08-08 journal: Semin Cell Dev Biol DOI: 10.1016/j.semcdb.2019.07.013 sha: doc_id: 276364 cord_uid: zyw5aukk file: cache/cord-271635-tydlyc1q.json key: cord-271635-tydlyc1q authors: Abdel-Hamid, Nabil M.; Abass, Shimaa A.; Mohamed, Ahmed A.; Muneam Hamid, Daniah title: Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors date: 2018-11-30 journal: Biomedicine & Pharmacotherapy DOI: 10.1016/j.biopha.2018.08.104 sha: doc_id: 271635 cord_uid: tydlyc1q file: cache/cord-273555-i1d4quos.json key: cord-273555-i1d4quos authors: Stättermayer, A. 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Govinda; Jeang, Kuan-Teh title: Viral and cellular RNA helicases as antiviral targets date: 2005-09-23 journal: Nat Rev Drug Discov DOI: 10.1038/nrd1853 sha: doc_id: 269294 cord_uid: vx7xr80t file: cache/cord-265005-e6rpryrh.json key: cord-265005-e6rpryrh authors: Tomasello, Elena; Pollet, Emeline; Vu Manh, Thien-Phong; Uzé, Gilles; Dalod, Marc title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 journal: Front Immunol DOI: 10.3389/fimmu.2014.00526 sha: doc_id: 265005 cord_uid: e6rpryrh file: cache/cord-292940-kg1rl6rb.json key: cord-292940-kg1rl6rb authors: Butt, Adeel A.; Yan, Peng title: Rates and Characteristics of SARS‐CoV‐2 Infection in Persons with Hepatitis C Virus Infection date: 2020-10-02 journal: Liver Int DOI: 10.1111/liv.14681 sha: doc_id: 292940 cord_uid: kg1rl6rb file: cache/cord-286719-1xjmlwqr.json key: cord-286719-1xjmlwqr authors: Draz, Mohamed Shehata; Shafiee, Hadi title: Applications of gold nanoparticles in virus detection date: 2018-02-15 journal: Theranostics DOI: 10.7150/thno.23856 sha: doc_id: 286719 cord_uid: 1xjmlwqr file: cache/cord-300642-c7adeis1.json key: cord-300642-c7adeis1 authors: Lai, Andrew SH; Lai, Kar Neng title: Viral nephropathy date: 2006 journal: Nat Clin Pract Nephrol DOI: 10.1038/ncpneph0166 sha: doc_id: 300642 cord_uid: c7adeis1 file: cache/cord-291321-ao80xk11.json key: cord-291321-ao80xk11 authors: Khan, Mohsin; Syed, Gulam Hussain; Kim, Seong-Jun; Siddiqui, Aleem title: Mitochondrial dynamics and viral infections: A close nexus date: 2015-10-31 journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research DOI: 10.1016/j.bbamcr.2014.12.040 sha: doc_id: 291321 cord_uid: ao80xk11 file: cache/cord-289321-ahl46ql9.json key: cord-289321-ahl46ql9 authors: van Buuren, Nicholas; Tellinghuisen, Timothy L; Richardson, Christopher D; Kirkegaard, Karla title: Transmission genetics of drug-resistant hepatitis C virus date: 2018-03-28 journal: eLife DOI: 10.7554/elife.32579 sha: doc_id: 289321 cord_uid: ahl46ql9 file: cache/cord-294842-aesiff1f.json key: cord-294842-aesiff1f authors: Romero-Brey, Inés; Bartenschlager, Ralf title: Membranous Replication Factories Induced by Plus-Strand RNA Viruses date: 2014-07-22 journal: Viruses DOI: 10.3390/v6072826 sha: doc_id: 294842 cord_uid: aesiff1f file: cache/cord-284551-j0nooxmd.json key: cord-284551-j0nooxmd authors: Shinohara, Yoshiyasu; Imajo, Kento; Yoneda, Masato; Tomeno, Wataru; Ogawa, Yuji; Kirikoshi, Hiroyuki; Funakoshi, Kengo; Ikeda, Masanori; Kato, Nobuyuki; Nakajima, Atsushi; Saito, Satoru title: Unfolded protein response pathways regulate Hepatitis C virus replication via modulation of autophagy date: 2013-03-08 journal: Biochem Biophys Res Commun DOI: 10.1016/j.bbrc.2013.01.103 sha: doc_id: 284551 cord_uid: j0nooxmd file: cache/cord-299747-qovrstak.json key: cord-299747-qovrstak authors: Deval, Jerome; Symons, Julian A; Beigelman, Leo title: Inhibition of viral RNA polymerases by nucleoside and nucleotide analogs: therapeutic applications against positive-strand RNA viruses beyond hepatitis C virus date: 2014-09-17 journal: Curr Opin Virol DOI: 10.1016/j.coviro.2014.08.004 sha: doc_id: 299747 cord_uid: qovrstak file: cache/cord-293790-7hyelm88.json key: cord-293790-7hyelm88 authors: Guévin, Carl; Manna, David; Bélanger, Claudia; Konan, Kouacou V.; Mak, Paul; Labonté, Patrick title: Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection date: 2010-09-01 journal: Virology DOI: 10.1016/j.virol.2010.05.032 sha: doc_id: 293790 cord_uid: 7hyelm88 file: cache/cord-293653-u2qrxq6t.json key: cord-293653-u2qrxq6t authors: Watashi, Koichi; Shimotohno, Kunitada title: Cyclophilin and Viruses: Cyclophilin as a Cofactor for Viral Infection and Possible Anti-Viral Target date: 2007-02-05 journal: Drug Target Insights DOI: nan sha: doc_id: 293653 cord_uid: u2qrxq6t file: cache/cord-298033-kzdp9edn.json key: cord-298033-kzdp9edn authors: Domingo, Esteban title: Quasispecies dynamics in disease prevention and control date: 2019-11-08 journal: Virus as Populations DOI: 10.1016/b978-0-12-816331-3.00008-8 sha: doc_id: 298033 cord_uid: kzdp9edn file: cache/cord-293646-d4qcckh1.json key: cord-293646-d4qcckh1 authors: Meanwell, Nicholas A.; Serrano-Wu, Michael H.; Snyder, Lawrence B. title: Chapter 22. 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Oslo, Norway, 5–7 October 2016 date: 2017-01-10 journal: Int J Clin Pharm DOI: 10.1007/s11096-016-0404-4 sha: doc_id: 350571 cord_uid: 6tapkjb6 file: cache/cord-010092-uftc8inx.json key: cord-010092-uftc8inx authors: nan title: Abstract of 29th Regional Congress of the ISBT date: 2019-06-07 journal: Vox Sang DOI: 10.1111/vox.12792 sha: doc_id: 10092 cord_uid: uftc8inx file: cache/cord-010119-t1x9gknd.json key: cord-010119-t1x9gknd authors: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 journal: Transfusion DOI: 10.1111/trf.14286 sha: doc_id: 10119 cord_uid: t1x9gknd Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-hcv-cord cp: cannot stat ‘/data-disk/reader-compute/reader-cord/cord/wrd/cord-266105-8avkjc84.wrd’: No such file or directory cp: cannot stat ‘/data-disk/reader-compute/reader-cord/cord/pos/cord-266105-8avkjc84.pos’: No such file or directory cp: cannot stat ‘/data-disk/reader-compute/reader-cord/cord/ent/cord-266105-8avkjc84.ent’: No such file or directory === file2bib.sh === Traceback (most recent call last): File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2646, in get_loc return self._engine.get_loc(key) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-266105-8avkjc84' During handling of the above exception, another exception occurred: Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/file2bib.py", line 64, in if ( bibliographics.loc[ escape ,'author'] ) : author = bibliographics.loc[ escape,'author'] File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1762, in __getitem__ return self._getitem_tuple(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1272, in _getitem_tuple return self._getitem_lowerdim(tup) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1389, in _getitem_lowerdim section = self._getitem_axis(key, axis=i) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1965, in _getitem_axis return self._get_label(key, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 625, in _get_label return self.obj._xs(label, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/generic.py", line 3537, in xs loc = self.index.get_loc(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2648, in get_loc return self._engine.get_loc(self._maybe_cast_indexer(key)) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-266105-8avkjc84' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73476 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === Traceback (most recent call last): File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2646, in get_loc return self._engine.get_loc(key) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-266738-8xx1xm2d' During handling of the above exception, another exception occurred: Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/file2bib.py", line 64, in if ( bibliographics.loc[ escape ,'author'] ) : author = bibliographics.loc[ escape,'author'] File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1762, in __getitem__ return self._getitem_tuple(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1272, in _getitem_tuple return self._getitem_lowerdim(tup) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1389, in _getitem_lowerdim section = self._getitem_axis(key, axis=i) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1965, in _getitem_axis return self._get_label(key, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 625, in _get_label return self.obj._xs(label, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/generic.py", line 3537, in xs loc = self.index.get_loc(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2648, in get_loc return self._engine.get_loc(self._maybe_cast_indexer(key)) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-266738-8xx1xm2d' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73178 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75043 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74433 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74121 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74033 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73445 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74595 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73520 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73697 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74215 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74143 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74373 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72679 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74816 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73186 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-000174-mgj9zfft author: Slavenburg, Serena title: Pneumonitis as A Consequence of (Peg)Interferon-Ribavirin Combination Therapy for Hepatitis C: a Review of the Literature date: 2009-04-28 pages: extension: .txt txt: ./txt/cord-000174-mgj9zfft.txt cache: ./cache/cord-000174-mgj9zfft.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000174-mgj9zfft.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74949 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-007305-pkjfnhro author: Iosub, Silvia title: Leukonychia Partialis in Kawasaki Disease date: 1984-10-17 pages: extension: .txt txt: ./txt/cord-007305-pkjfnhro.txt cache: ./cache/cord-007305-pkjfnhro.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007305-pkjfnhro.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73479 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72612 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-005617-bxbogskm author: Conway, Anna title: Hepatitis C Screening in Community-Based Voluntary Counselling and Testing Services in Europe: An Observational Study from the COBATEST Network 2014–2018 date: 2019-11-20 pages: extension: .txt txt: ./txt/cord-005617-bxbogskm.txt cache: ./cache/cord-005617-bxbogskm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005617-bxbogskm.txt' === file2bib.sh === id: cord-001834-6xf4o3oy author: Sung, Pil Soo title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection date: 2015-10-07 pages: extension: .txt txt: ./txt/cord-001834-6xf4o3oy.txt cache: ./cache/cord-001834-6xf4o3oy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-001834-6xf4o3oy.txt' === file2bib.sh === id: cord-273555-i1d4quos author: Stättermayer, A. F. title: Letter: does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks? Authors' reply date: 2014-02-04 pages: extension: .txt txt: ./txt/cord-273555-i1d4quos.txt cache: ./cache/cord-273555-i1d4quos.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273555-i1d4quos.txt' === file2bib.sh === id: cord-006061-z9r5htm9 author: Hu, Bo title: HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation date: 2016-06-17 pages: extension: .txt txt: ./txt/cord-006061-z9r5htm9.txt cache: ./cache/cord-006061-z9r5htm9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-006061-z9r5htm9.txt' === file2bib.sh === id: cord-001421-6t5puo6p author: Marfà, Santiago title: Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date: 2014-10-02 pages: extension: .txt txt: ./txt/cord-001421-6t5puo6p.txt cache: ./cache/cord-001421-6t5puo6p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-001421-6t5puo6p.txt' === file2bib.sh === id: cord-006436-61mgtbj4 author: Yoshiba, Makoto title: Development of reliable artificial liver support (ALS)-plasma exchange in combination with hemodiafiltration using high-performance membranes date: 1993 pages: extension: .txt txt: ./txt/cord-006436-61mgtbj4.txt cache: ./cache/cord-006436-61mgtbj4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-006436-61mgtbj4.txt' === file2bib.sh === id: cord-258234-qn8xp4v9 author: Striker, Rob title: Inhibitors of Peptidyl Proline Isomerases As Antivirals in Hepatitis C and Other Viruses date: 2014-11-06 pages: extension: .txt txt: ./txt/cord-258234-qn8xp4v9.txt cache: ./cache/cord-258234-qn8xp4v9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258234-qn8xp4v9.txt' === file2bib.sh === id: cord-026112-58sa5z03 author: Dehghani-Dehej, Farzaneh title: Prevalence of HCV and/or HBV coinfection in Iranian HIV-infected patients date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-026112-58sa5z03.txt cache: ./cache/cord-026112-58sa5z03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-026112-58sa5z03.txt' === file2bib.sh === id: cord-000833-m6abyuvx author: Sekiguchi, Satoshi title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date: 2012-12-17 pages: extension: .txt txt: ./txt/cord-000833-m6abyuvx.txt cache: ./cache/cord-000833-m6abyuvx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000833-m6abyuvx.txt' === file2bib.sh === id: cord-003158-mhlqnj52 author: Wang, Qi title: Adapted HCV JFH1 variant is capable of accommodating a large foreign gene insert and allows lower level HCV replication and viral production date: 2018-07-13 pages: extension: .txt txt: ./txt/cord-003158-mhlqnj52.txt cache: ./cache/cord-003158-mhlqnj52.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003158-mhlqnj52.txt' === file2bib.sh === id: cord-279202-iyteg4h9 author: Shesheer Kumar, Munpally title: Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients date: 2008-01-05 pages: extension: .txt txt: ./txt/cord-279202-iyteg4h9.txt cache: ./cache/cord-279202-iyteg4h9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279202-iyteg4h9.txt' === file2bib.sh === id: cord-000008-3dgjv0x1 author: Vali, Bahareh title: HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date: 2008-10-20 pages: extension: .txt txt: ./txt/cord-000008-3dgjv0x1.txt cache: ./cache/cord-000008-3dgjv0x1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000008-3dgjv0x1.txt' === file2bib.sh === id: cord-000638-ss1435el author: Beq, Stephanie title: Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date: 2012-04-16 pages: extension: .txt txt: ./txt/cord-000638-ss1435el.txt cache: ./cache/cord-000638-ss1435el.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000638-ss1435el.txt' === file2bib.sh === id: cord-003407-f5v3hhr8 author: Hung, Ting-Chun title: Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date: 2018-11-27 pages: extension: .txt txt: ./txt/cord-003407-f5v3hhr8.txt cache: ./cache/cord-003407-f5v3hhr8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003407-f5v3hhr8.txt' === file2bib.sh === id: cord-261287-l4649du3 author: Puoti, Massimo title: A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients() date: 2004-05-06 pages: extension: .txt txt: ./txt/cord-261287-l4649du3.txt cache: ./cache/cord-261287-l4649du3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261287-l4649du3.txt' === file2bib.sh === id: cord-007236-8hiymqyb author: Sun, Ji-Min title: Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway date: 2011-11-09 pages: extension: .txt txt: ./txt/cord-007236-8hiymqyb.txt cache: ./cache/cord-007236-8hiymqyb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007236-8hiymqyb.txt' === file2bib.sh === id: cord-002369-shk4n8f6 author: Fahmy, Ahmed M. title: The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date: 2017-01-09 pages: extension: .txt txt: ./txt/cord-002369-shk4n8f6.txt cache: ./cache/cord-002369-shk4n8f6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002369-shk4n8f6.txt' === file2bib.sh === id: cord-000473-jpow6iw1 author: Astrovskaya, Irina title: Inferring viral quasispecies spectra from 454 pyrosequencing reads date: 2011-07-28 pages: extension: .txt txt: ./txt/cord-000473-jpow6iw1.txt cache: ./cache/cord-000473-jpow6iw1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000473-jpow6iw1.txt' === file2bib.sh === id: cord-260099-mthwab4p author: Li, Yi title: C-type lectin LSECtin interacts with DC-SIGNR and is involved in hepatitis C virus binding date: 2009-02-21 pages: extension: .txt txt: ./txt/cord-260099-mthwab4p.txt cache: ./cache/cord-260099-mthwab4p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260099-mthwab4p.txt' === file2bib.sh === id: cord-011182-nbtfb39r author: Dehghani, Behzad title: Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran date: 2019-04-20 pages: extension: .txt txt: ./txt/cord-011182-nbtfb39r.txt cache: ./cache/cord-011182-nbtfb39r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011182-nbtfb39r.txt' === file2bib.sh === id: cord-018220-8m11ig06 author: Duncan, Coley B. title: Viral Infections date: 2009-02-02 pages: extension: .txt txt: ./txt/cord-018220-8m11ig06.txt cache: ./cache/cord-018220-8m11ig06.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-018220-8m11ig06.txt' === file2bib.sh === id: cord-011026-iapgkz0p author: El-Bitar, Alaa M. H. title: Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus date: 2019-07-06 pages: extension: .txt txt: ./txt/cord-011026-iapgkz0p.txt cache: ./cache/cord-011026-iapgkz0p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-011026-iapgkz0p.txt' === file2bib.sh === id: cord-265588-1tcaleeo author: Yousaf, Tahir title: Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus date: 2018-03-20 pages: extension: .txt txt: ./txt/cord-265588-1tcaleeo.txt cache: ./cache/cord-265588-1tcaleeo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265588-1tcaleeo.txt' === file2bib.sh === id: cord-000786-ofpcgxce author: Chua, Brendon Y. title: Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses date: 2012-10-16 pages: extension: .txt txt: ./txt/cord-000786-ofpcgxce.txt cache: ./cache/cord-000786-ofpcgxce.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000786-ofpcgxce.txt' === file2bib.sh === id: cord-284904-qw1ig2v4 author: Mizui, Tomokazu title: Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy date: 2009-09-17 pages: extension: .txt txt: ./txt/cord-284904-qw1ig2v4.txt cache: ./cache/cord-284904-qw1ig2v4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284904-qw1ig2v4.txt' === file2bib.sh === id: cord-002410-2zi5iv2t author: Bruening, Janina title: The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy date: 2017-02-01 pages: extension: .txt txt: ./txt/cord-002410-2zi5iv2t.txt cache: ./cache/cord-002410-2zi5iv2t.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002410-2zi5iv2t.txt' === file2bib.sh === id: cord-013244-d6saaiu9 author: Eijsink, Job F. H. title: Cost-effectiveness of hepatitis C virus screening, and subsequent monitoring or treatment among pregnant women in the Netherlands date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-013244-d6saaiu9.txt cache: ./cache/cord-013244-d6saaiu9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013244-d6saaiu9.txt' === file2bib.sh === id: cord-006129-5rog0s98 author: Hemida, Maged Gomaa title: Exploiting the Therapeutic Potential of MicroRNAs in Viral Diseases: Expectations and Limitations date: 2012-08-16 pages: extension: .txt txt: ./txt/cord-006129-5rog0s98.txt cache: ./cache/cord-006129-5rog0s98.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006129-5rog0s98.txt' === file2bib.sh === id: cord-001848-idmj2d7p author: Onabajo, Olusegun O. title: Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date: 2015-11-01 pages: extension: .txt txt: ./txt/cord-001848-idmj2d7p.txt cache: ./cache/cord-001848-idmj2d7p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001848-idmj2d7p.txt' === file2bib.sh === id: cord-264936-3posyr5n author: Mohammadzadeh, Sara title: Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications date: 2014-11-24 pages: extension: .txt txt: ./txt/cord-264936-3posyr5n.txt cache: ./cache/cord-264936-3posyr5n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264936-3posyr5n.txt' === file2bib.sh === id: cord-005138-u2lwgyyf author: Kou, Yi-Hen title: Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A date: 2006-08-23 pages: extension: .txt txt: ./txt/cord-005138-u2lwgyyf.txt cache: ./cache/cord-005138-u2lwgyyf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005138-u2lwgyyf.txt' === file2bib.sh === id: cord-264713-38dlh3wg author: Vernet, Guy title: Molecular diagnostics in virology date: 2004-08-20 pages: extension: .txt txt: ./txt/cord-264713-38dlh3wg.txt cache: ./cache/cord-264713-38dlh3wg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264713-38dlh3wg.txt' === file2bib.sh === id: cord-284978-vh1x6pg9 author: Jang, Hongje title: Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide date: 2013-02-18 pages: extension: .txt txt: ./txt/cord-284978-vh1x6pg9.txt cache: ./cache/cord-284978-vh1x6pg9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284978-vh1x6pg9.txt' === file2bib.sh === id: cord-264326-teahway7 author: Eleftheriou, Phaedra title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-264326-teahway7.txt cache: ./cache/cord-264326-teahway7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264326-teahway7.txt' === file2bib.sh === id: cord-030361-0tepkjdl author: Mohammed Abdul, Mubeen Khan title: Hepatitis C Virus in the Elderly in the Direct-Acting Antiviral Era: from Diagnosis to Cure date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-030361-0tepkjdl.txt cache: ./cache/cord-030361-0tepkjdl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-030361-0tepkjdl.txt' === file2bib.sh === Traceback (most recent call last): File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2646, in get_loc return self._engine.get_loc(key) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-324559-p92y5er2' During handling of the above exception, another exception occurred: Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/file2bib.py", line 64, in if ( bibliographics.loc[ escape ,'author'] ) : author = bibliographics.loc[ escape,'author'] File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1762, in __getitem__ return self._getitem_tuple(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1272, in _getitem_tuple return self._getitem_lowerdim(tup) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1389, in _getitem_lowerdim section = self._getitem_axis(key, axis=i) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1965, in _getitem_axis return self._get_label(key, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 625, in _get_label return self.obj._xs(label, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/generic.py", line 3537, in xs loc = self.index.get_loc(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2648, in get_loc return self._engine.get_loc(self._maybe_cast_indexer(key)) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-324559-p92y5er2' === file2bib.sh === id: cord-253768-y35m3vh1 author: Springer, Sandra A title: Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA’s Advocacy Agenda date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-253768-y35m3vh1.txt cache: ./cache/cord-253768-y35m3vh1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253768-y35m3vh1.txt' === file2bib.sh === id: cord-268467-btfz6ye8 author: Schreiber, Steven S. title: Sequence analysis of the nucleocapsid protein gene of human coronavirus 229E date: 1989-03-31 pages: extension: .txt txt: ./txt/cord-268467-btfz6ye8.txt cache: ./cache/cord-268467-btfz6ye8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-268467-btfz6ye8.txt' === file2bib.sh === id: cord-270498-hh6h50t2 author: Tseng, Chin-Kai title: Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date: 2017-09-19 pages: extension: .txt txt: ./txt/cord-270498-hh6h50t2.txt cache: ./cache/cord-270498-hh6h50t2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270498-hh6h50t2.txt' === file2bib.sh === id: cord-009263-w8bmmgtj author: Colpitts, Che C. title: Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process date: 2020-03-18 pages: extension: .txt txt: ./txt/cord-009263-w8bmmgtj.txt cache: ./cache/cord-009263-w8bmmgtj.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-009263-w8bmmgtj.txt' === file2bib.sh === id: cord-024003-698d15gk author: Loutfy, Samah A title: Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-024003-698d15gk.txt cache: ./cache/cord-024003-698d15gk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-024003-698d15gk.txt' === file2bib.sh === id: cord-003993-3bozjfv7 author: Cagliani, Rachele title: Mode and tempo of human hepatitis virus evolution date: 2019-10-25 pages: extension: .txt txt: ./txt/cord-003993-3bozjfv7.txt cache: ./cache/cord-003993-3bozjfv7.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003993-3bozjfv7.txt' === file2bib.sh === id: cord-000830-jiy4cp4n author: Cobo, Fernando title: Application of Molecular Diagnostic Techniques for Viral Testing date: 2012-11-30 pages: extension: .txt txt: ./txt/cord-000830-jiy4cp4n.txt cache: ./cache/cord-000830-jiy4cp4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000830-jiy4cp4n.txt' === file2bib.sh === id: cord-259916-gr6v098c author: Wang, Hongliang title: Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication date: 2016-05-20 pages: extension: .txt txt: ./txt/cord-259916-gr6v098c.txt cache: ./cache/cord-259916-gr6v098c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-259916-gr6v098c.txt' === file2bib.sh === id: cord-255781-55zrmgxq author: Bergman, Scott J. title: Interferons as Therapeutic Agents for Infectious Diseases date: 2011-12-31 pages: extension: .txt txt: ./txt/cord-255781-55zrmgxq.txt cache: ./cache/cord-255781-55zrmgxq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255781-55zrmgxq.txt' === file2bib.sh === id: cord-010273-0c56x9f5 author: Simmonds, Peter title: Virology of hepatitis C virus date: 2001-10-10 pages: extension: .txt txt: ./txt/cord-010273-0c56x9f5.txt cache: ./cache/cord-010273-0c56x9f5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-010273-0c56x9f5.txt' === file2bib.sh === id: cord-015941-4fz79wzf author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2018-11-10 pages: extension: .txt txt: ./txt/cord-015941-4fz79wzf.txt cache: ./cache/cord-015941-4fz79wzf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-015941-4fz79wzf.txt' === file2bib.sh === id: cord-280330-ibvbowl0 author: Lin, Liang-Tzung title: Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry date: 2013-08-07 pages: extension: .txt txt: ./txt/cord-280330-ibvbowl0.txt cache: ./cache/cord-280330-ibvbowl0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280330-ibvbowl0.txt' === file2bib.sh === id: cord-017948-fqhl1qb4 author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2012-04-05 pages: extension: .txt txt: ./txt/cord-017948-fqhl1qb4.txt cache: ./cache/cord-017948-fqhl1qb4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-017948-fqhl1qb4.txt' === file2bib.sh === id: cord-017506-t86v3zw3 author: Knox, Tamsin A. title: Alcohol, HIV/AIDS, and Liver Disease date: 2012-04-27 pages: extension: .txt txt: ./txt/cord-017506-t86v3zw3.txt cache: ./cache/cord-017506-t86v3zw3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017506-t86v3zw3.txt' === file2bib.sh === id: cord-281389-sht0yx4a author: Tal, Michal Caspi title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-281389-sht0yx4a.txt cache: ./cache/cord-281389-sht0yx4a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281389-sht0yx4a.txt' === file2bib.sh === id: cord-256036-gd53s4dv author: Sandmann, Lisa title: Barriers of hepatitis C virus interspecies transmission date: 2013-01-01 pages: extension: .txt txt: ./txt/cord-256036-gd53s4dv.txt cache: ./cache/cord-256036-gd53s4dv.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256036-gd53s4dv.txt' === file2bib.sh === id: cord-013176-6ckuya1w author: Ninfali, Paolino title: Antiviral Properties of Flavonoids and Delivery Strategies date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-013176-6ckuya1w.txt cache: ./cache/cord-013176-6ckuya1w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013176-6ckuya1w.txt' === file2bib.sh === id: cord-016343-wc3i54fc author: Frese, Michael title: Interferon-Induced Effector Proteins and Hepatitis C Virus Replication date: 2008 pages: extension: .txt txt: ./txt/cord-016343-wc3i54fc.txt cache: ./cache/cord-016343-wc3i54fc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016343-wc3i54fc.txt' === file2bib.sh === id: cord-018785-tcr5xlf8 author: Nambiar, Puja title: Infection in Kidney Transplantation date: 2018-06-27 pages: extension: .txt txt: ./txt/cord-018785-tcr5xlf8.txt cache: ./cache/cord-018785-tcr5xlf8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018785-tcr5xlf8.txt' === file2bib.sh === id: cord-017764-h1w9gbxk author: Meanwell, Nicholas A. title: The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex date: 2018-06-08 pages: extension: .txt txt: ./txt/cord-017764-h1w9gbxk.txt cache: ./cache/cord-017764-h1w9gbxk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017764-h1w9gbxk.txt' === file2bib.sh === id: cord-307556-k2lavvca author: Jang, Hongje title: Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide date: 2013-02-18 pages: extension: .txt txt: ./txt/cord-307556-k2lavvca.txt cache: ./cache/cord-307556-k2lavvca.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307556-k2lavvca.txt' === file2bib.sh === id: cord-253825-d9borky8 author: Blaising, Julie title: Arbidol as a broad-spectrum antiviral: An update date: 2014-04-24 pages: extension: .txt txt: ./txt/cord-253825-d9borky8.txt cache: ./cache/cord-253825-d9borky8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-253825-d9borky8.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 80047 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-267867-q52nvn0n author: Chevalier, Christophe title: Inhibition of Hepatitis C Virus Infection in Cell Culture by Small Interfering RNAs date: 2016-12-14 pages: extension: .txt txt: ./txt/cord-267867-q52nvn0n.txt cache: ./cache/cord-267867-q52nvn0n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267867-q52nvn0n.txt' === file2bib.sh === id: cord-284693-mgpxnnk0 author: Jothimani, Dinesh title: Post Liver transplant recurrent and de novo viral infections date: 2020-09-26 pages: extension: .txt txt: ./txt/cord-284693-mgpxnnk0.txt cache: ./cache/cord-284693-mgpxnnk0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284693-mgpxnnk0.txt' === file2bib.sh === id: cord-293646-d4qcckh1 author: Meanwell, Nicholas A. title: Chapter 22. Non-HIV antiviral agents date: 2003-12-31 pages: extension: .txt txt: ./txt/cord-293646-d4qcckh1.txt cache: ./cache/cord-293646-d4qcckh1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293646-d4qcckh1.txt' === file2bib.sh === id: cord-299719-bvdsz626 author: Fournier, C. title: Are trans‐complementation systems suitable for hepatitis C virus life cycle studies? date: 2013-02-14 pages: extension: .txt txt: ./txt/cord-299719-bvdsz626.txt cache: ./cache/cord-299719-bvdsz626.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299719-bvdsz626.txt' === file2bib.sh === id: cord-293653-u2qrxq6t author: Watashi, Koichi title: Cyclophilin and Viruses: Cyclophilin as a Cofactor for Viral Infection and Possible Anti-Viral Target date: 2007-02-05 pages: extension: .txt txt: ./txt/cord-293653-u2qrxq6t.txt cache: ./cache/cord-293653-u2qrxq6t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293653-u2qrxq6t.txt' === file2bib.sh === id: cord-325989-nf6ouaq3 author: Es-Saad, Salwa title: Regulators of innate immunity as novel targets for panviral therapeutics date: 2012-09-24 pages: extension: .txt txt: ./txt/cord-325989-nf6ouaq3.txt cache: ./cache/cord-325989-nf6ouaq3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325989-nf6ouaq3.txt' === file2bib.sh === id: cord-293790-7hyelm88 author: Guévin, Carl title: Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection date: 2010-09-01 pages: extension: .txt txt: ./txt/cord-293790-7hyelm88.txt cache: ./cache/cord-293790-7hyelm88.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293790-7hyelm88.txt' === file2bib.sh === id: cord-314753-xflhxb13 author: Manso, Carmen F. title: Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date: 2017-06-23 pages: extension: .txt txt: ./txt/cord-314753-xflhxb13.txt cache: ./cache/cord-314753-xflhxb13.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-314753-xflhxb13.txt' === file2bib.sh === id: cord-324054-d71rj29o author: Zhang, Xuming title: The hemagglutinin/esterase gene of human coronavirus strain OC43: Phylogenetic relationships to bovine and murine coronaviruses and influenza C virus date: 1992-01-31 pages: extension: .txt txt: ./txt/cord-324054-d71rj29o.txt cache: ./cache/cord-324054-d71rj29o.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324054-d71rj29o.txt' === file2bib.sh === id: cord-291321-ao80xk11 author: Khan, Mohsin title: Mitochondrial dynamics and viral infections: A close nexus date: 2015-10-31 pages: extension: .txt txt: ./txt/cord-291321-ao80xk11.txt cache: ./cache/cord-291321-ao80xk11.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-291321-ao80xk11.txt' === file2bib.sh === id: cord-316968-rowoylge author: Zhang, Wenjuan title: Using maximum likelihood method to detect adaptive evolution of HCV envelope protein-coding genes date: 2006 pages: extension: .txt txt: ./txt/cord-316968-rowoylge.txt cache: ./cache/cord-316968-rowoylge.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316968-rowoylge.txt' === file2bib.sh === id: cord-316703-8kxx3034 author: Parera, Mariona title: Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date: 2012-08-01 pages: extension: .txt txt: ./txt/cord-316703-8kxx3034.txt cache: ./cache/cord-316703-8kxx3034.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316703-8kxx3034.txt' === file2bib.sh === id: cord-305263-fgwf6wy3 author: Wang, Ben X. title: The yin and yang of viruses and interferons date: 2012-02-07 pages: extension: .txt txt: ./txt/cord-305263-fgwf6wy3.txt cache: ./cache/cord-305263-fgwf6wy3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-305263-fgwf6wy3.txt' === file2bib.sh === id: cord-321230-b5a1z14w author: Samji, Hasina title: Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-321230-b5a1z14w.txt cache: ./cache/cord-321230-b5a1z14w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-321230-b5a1z14w.txt' === file2bib.sh === id: cord-343902-hzh3cjzh author: Peel, Michael title: Cyclophilin inhibitors as antiviral agents date: 2013-08-15 pages: extension: .txt txt: ./txt/cord-343902-hzh3cjzh.txt cache: ./cache/cord-343902-hzh3cjzh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343902-hzh3cjzh.txt' === file2bib.sh === id: cord-314148-5xisw9au author: Hasony, Hassan J. title: Prevalence of human coronavirus antibody in the population of southern iraq date: 2005-12-06 pages: extension: .txt txt: ./txt/cord-314148-5xisw9au.txt cache: ./cache/cord-314148-5xisw9au.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314148-5xisw9au.txt' === file2bib.sh === id: cord-285868-fz5utxss author: Jheng, Jia-Rong title: ER stress, autophagy, and RNA viruses date: 2014-08-05 pages: extension: .txt txt: ./txt/cord-285868-fz5utxss.txt cache: ./cache/cord-285868-fz5utxss.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285868-fz5utxss.txt' === file2bib.sh === id: cord-306934-29ljbl7g author: Tonelli, Michele title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date: 2009-07-01 pages: extension: .txt txt: ./txt/cord-306934-29ljbl7g.txt cache: ./cache/cord-306934-29ljbl7g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-306934-29ljbl7g.txt' === file2bib.sh === id: cord-335085-7pxkhgbq author: Dessau, R. B. title: Coronaviruses in spinal fluid of patients with acute monosymptomatic optic neuritis date: 2009-01-29 pages: extension: .txt txt: ./txt/cord-335085-7pxkhgbq.txt cache: ./cache/cord-335085-7pxkhgbq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335085-7pxkhgbq.txt' === file2bib.sh === id: cord-300154-3p7tjp5j author: Pezacki, John Paul title: Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy date: 2011-02-14 pages: extension: .txt txt: ./txt/cord-300154-3p7tjp5j.txt cache: ./cache/cord-300154-3p7tjp5j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300154-3p7tjp5j.txt' === file2bib.sh === id: cord-350600-73q8mve4 author: Myint, S. title: Detection of human coronavirus 229E in nasal washings using RNA:RNA hybridization date: 2005-12-09 pages: extension: .txt txt: ./txt/cord-350600-73q8mve4.txt cache: ./cache/cord-350600-73q8mve4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-350600-73q8mve4.txt' === file2bib.sh === id: cord-294842-aesiff1f author: Romero-Brey, Inés title: Membranous Replication Factories Induced by Plus-Strand RNA Viruses date: 2014-07-22 pages: extension: .txt txt: ./txt/cord-294842-aesiff1f.txt cache: ./cache/cord-294842-aesiff1f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294842-aesiff1f.txt' === file2bib.sh === id: cord-321505-m40s6uw9 author: Sakamoto, Naoya title: Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA date: 2007-08-07 pages: extension: .txt txt: ./txt/cord-321505-m40s6uw9.txt cache: ./cache/cord-321505-m40s6uw9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321505-m40s6uw9.txt' === file2bib.sh === id: cord-334493-rt7gqiev author: Ikejiri, Masahiro title: 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents date: 2007-11-15 pages: extension: .txt txt: ./txt/cord-334493-rt7gqiev.txt cache: ./cache/cord-334493-rt7gqiev.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334493-rt7gqiev.txt' === file2bib.sh === id: cord-307817-2vy28i4m author: Lou, Zhiyong title: Current progress in antiviral strategies date: 2014-01-14 pages: extension: .txt txt: ./txt/cord-307817-2vy28i4m.txt cache: ./cache/cord-307817-2vy28i4m.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307817-2vy28i4m.txt' === file2bib.sh === id: cord-326217-ji0njeha author: Saleh, Maged title: Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122 date: 2018-11-27 pages: extension: .txt txt: ./txt/cord-326217-ji0njeha.txt cache: ./cache/cord-326217-ji0njeha.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326217-ji0njeha.txt' === file2bib.sh === id: cord-347319-lcuma3eh author: Ashfaq, Usman A title: Lysosomotropic agents as HCV entry inhibitors date: 2011-04-12 pages: extension: .txt txt: ./txt/cord-347319-lcuma3eh.txt cache: ./cache/cord-347319-lcuma3eh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347319-lcuma3eh.txt' === file2bib.sh === id: cord-312080-pu6m4qad author: He, Bing title: Three-dimensional cell culture models for investigating human viruses date: 2016-10-27 pages: extension: .txt txt: ./txt/cord-312080-pu6m4qad.txt cache: ./cache/cord-312080-pu6m4qad.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312080-pu6m4qad.txt' === file2bib.sh === id: cord-307934-84zfabti author: Lai, Chao-Kuen title: Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date: 2014-06-06 pages: extension: .txt txt: ./txt/cord-307934-84zfabti.txt cache: ./cache/cord-307934-84zfabti.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307934-84zfabti.txt' === file2bib.sh === id: cord-323963-whv88ggl author: Fan, Xiaofeng title: Efficient amplification and cloning of near full-length hepatitis C virus genome from clinical samples date: 2006-08-11 pages: extension: .txt txt: ./txt/cord-323963-whv88ggl.txt cache: ./cache/cord-323963-whv88ggl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323963-whv88ggl.txt' === file2bib.sh === id: cord-311823-85wj08gr author: Katze, Michael G. title: Innate immune modulation by RNA viruses: emerging insights from functional genomics date: 2008 pages: extension: .txt txt: ./txt/cord-311823-85wj08gr.txt cache: ./cache/cord-311823-85wj08gr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311823-85wj08gr.txt' === file2bib.sh === id: cord-314254-9ye8tfvz author: Pfaender, Stephanie title: Natural reservoirs for homologs of hepatitis C virus date: 2014-03-26 pages: extension: .txt txt: ./txt/cord-314254-9ye8tfvz.txt cache: ./cache/cord-314254-9ye8tfvz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314254-9ye8tfvz.txt' === file2bib.sh === id: cord-341071-nwrl1qws author: Berzal-Herranz, Alfredo title: Two Examples of RNA Aptamers with Antiviral Activity. Are Aptamers the Wished Antiviral Drugs? date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-341071-nwrl1qws.txt cache: ./cache/cord-341071-nwrl1qws.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341071-nwrl1qws.txt' === file2bib.sh === id: cord-305303-82n96ukr author: Shapira, Assaf title: Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date: 2012-02-16 pages: extension: .txt txt: ./txt/cord-305303-82n96ukr.txt cache: ./cache/cord-305303-82n96ukr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305303-82n96ukr.txt' === file2bib.sh === id: cord-333331-ddcz7zck author: Yang, Jin title: Detection of hepatitis C virus by an improved loop-mediated isothermal amplification assay date: 2011-05-12 pages: extension: .txt txt: ./txt/cord-333331-ddcz7zck.txt cache: ./cache/cord-333331-ddcz7zck.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333331-ddcz7zck.txt' === file2bib.sh === id: cord-305393-96mrxt8a author: Lai, Yvonne title: Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date: 2011-10-10 pages: extension: .txt txt: ./txt/cord-305393-96mrxt8a.txt cache: ./cache/cord-305393-96mrxt8a.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305393-96mrxt8a.txt' === file2bib.sh === id: cord-345898-a6vt8kso author: Ren, Linzhu title: Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses date: 2016-01-04 pages: extension: .txt txt: ./txt/cord-345898-a6vt8kso.txt cache: ./cache/cord-345898-a6vt8kso.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-345898-a6vt8kso.txt' === file2bib.sh === id: cord-321053-lgae22f8 author: Gerold, Gisa title: Opportunities and Risks of Host-targeting Antiviral Strategies for Hepatitis C date: 2013-10-04 pages: extension: .txt txt: ./txt/cord-321053-lgae22f8.txt cache: ./cache/cord-321053-lgae22f8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321053-lgae22f8.txt' === file2bib.sh === id: cord-351365-dc9t3vh3 author: Todt, Daniel title: Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date: 2016-10-13 pages: extension: .txt txt: ./txt/cord-351365-dc9t3vh3.txt cache: ./cache/cord-351365-dc9t3vh3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351365-dc9t3vh3.txt' === file2bib.sh === id: cord-314567-purplsjn author: Fernández-Ponce, Cecilia title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells date: 2018-01-04 pages: extension: .txt txt: ./txt/cord-314567-purplsjn.txt cache: ./cache/cord-314567-purplsjn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314567-purplsjn.txt' === file2bib.sh === id: cord-332422-s15o0hie author: Belouzard, Sandrine title: Hepatitis C virus entry into the hepatocyte date: 2011-11-07 pages: extension: .txt txt: ./txt/cord-332422-s15o0hie.txt cache: ./cache/cord-332422-s15o0hie.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332422-s15o0hie.txt' === file2bib.sh === id: cord-337285-t6qr41wc author: Ikeda, Masanori title: Modulation of host metabolism as a target of new antivirals() date: 2007-10-10 pages: extension: .txt txt: ./txt/cord-337285-t6qr41wc.txt cache: ./cache/cord-337285-t6qr41wc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337285-t6qr41wc.txt' === file2bib.sh === id: cord-305039-grsv06j7 author: Flego, Michela title: Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases date: 2013-01-04 pages: extension: .txt txt: ./txt/cord-305039-grsv06j7.txt cache: ./cache/cord-305039-grsv06j7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 19 resourceName b'cord-305039-grsv06j7.txt' === file2bib.sh === id: cord-280878-1kt51viz author: To, Janet title: Targeting the Channel Activity of Viroporins date: 2016-01-07 pages: extension: .txt txt: ./txt/cord-280878-1kt51viz.txt cache: ./cache/cord-280878-1kt51viz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280878-1kt51viz.txt' === file2bib.sh === id: cord-022380-49oti4zg author: Panlilio, Adelisa L title: Occupational Infectious Diseases date: 2009-05-15 pages: extension: .txt txt: ./txt/cord-022380-49oti4zg.txt cache: ./cache/cord-022380-49oti4zg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-022380-49oti4zg.txt' === file2bib.sh === id: cord-302295-nblmshni author: Savva, Athina title: Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases date: 2013-11-18 pages: extension: .txt txt: ./txt/cord-302295-nblmshni.txt cache: ./cache/cord-302295-nblmshni.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302295-nblmshni.txt' === file2bib.sh === id: cord-317595-siwzjeea author: Forni, Diego title: Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV date: 2018-05-01 pages: extension: .txt txt: ./txt/cord-317595-siwzjeea.txt cache: ./cache/cord-317595-siwzjeea.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317595-siwzjeea.txt' === file2bib.sh === id: cord-327135-4c2flue4 author: Chinnaswamy, S title: Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections date: 2016-06-09 pages: extension: .txt txt: ./txt/cord-327135-4c2flue4.txt cache: ./cache/cord-327135-4c2flue4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327135-4c2flue4.txt' === file2bib.sh === id: cord-298736-9bvyp21d author: Gerold, Gisa title: Decoding protein networks during virus entry by quantitative proteomics date: 2016-06-15 pages: extension: .txt txt: ./txt/cord-298736-9bvyp21d.txt cache: ./cache/cord-298736-9bvyp21d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298736-9bvyp21d.txt' === file2bib.sh === id: cord-303189-ktl4jw8v author: Coccia, Eliana M. title: Early IFN type I response: Learning from microbial evasion strategies date: 2015-03-31 pages: extension: .txt txt: ./txt/cord-303189-ktl4jw8v.txt cache: ./cache/cord-303189-ktl4jw8v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303189-ktl4jw8v.txt' === file2bib.sh === id: cord-319754-5isw53wl author: Balgoma, David title: Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update date: 2020-08-31 pages: extension: .txt txt: ./txt/cord-319754-5isw53wl.txt cache: ./cache/cord-319754-5isw53wl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319754-5isw53wl.txt' === file2bib.sh === id: cord-318853-mxyxwkhx author: Sallie, Richard title: Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases date: 2005-08-22 pages: extension: .txt txt: ./txt/cord-318853-mxyxwkhx.txt cache: ./cache/cord-318853-mxyxwkhx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-318853-mxyxwkhx.txt' === file2bib.sh === id: cord-286334-d9v5xtx7 author: Li, Rui title: Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-286334-d9v5xtx7.txt cache: ./cache/cord-286334-d9v5xtx7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-286334-d9v5xtx7.txt' === file2bib.sh === id: cord-342676-ykog278j author: Stewart, H. title: Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date: 2016-03-14 pages: extension: .txt txt: ./txt/cord-342676-ykog278j.txt cache: ./cache/cord-342676-ykog278j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342676-ykog278j.txt' === file2bib.sh === id: cord-274080-884x48on author: Rumlová, Michaela title: In vitro methods for testing antiviral drugs date: 2018-06-30 pages: extension: .txt txt: ./txt/cord-274080-884x48on.txt cache: ./cache/cord-274080-884x48on.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-274080-884x48on.txt' === file2bib.sh === id: cord-286719-1xjmlwqr author: Draz, Mohamed Shehata title: Applications of gold nanoparticles in virus detection date: 2018-02-15 pages: extension: .txt txt: ./txt/cord-286719-1xjmlwqr.txt cache: ./cache/cord-286719-1xjmlwqr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-286719-1xjmlwqr.txt' === file2bib.sh === id: cord-330110-pamxy4av author: Teissier, Elodie title: Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date: 2011-01-25 pages: extension: .txt txt: ./txt/cord-330110-pamxy4av.txt cache: ./cache/cord-330110-pamxy4av.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330110-pamxy4av.txt' === file2bib.sh === id: cord-332747-u46xryoo author: Mingorance, Lidia title: Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation date: 2018-09-18 pages: extension: .txt txt: ./txt/cord-332747-u46xryoo.txt cache: ./cache/cord-332747-u46xryoo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332747-u46xryoo.txt' === file2bib.sh === id: cord-340220-raqapqg0 author: Potel, Julie title: EWI‐2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry date: 2013-02-16 pages: extension: .txt txt: ./txt/cord-340220-raqapqg0.txt cache: ./cache/cord-340220-raqapqg0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340220-raqapqg0.txt' === file2bib.sh === id: cord-298033-kzdp9edn author: Domingo, Esteban title: Quasispecies dynamics in disease prevention and control date: 2019-11-08 pages: extension: .txt txt: ./txt/cord-298033-kzdp9edn.txt cache: ./cache/cord-298033-kzdp9edn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298033-kzdp9edn.txt' === file2bib.sh === id: cord-284376-plwyjhl8 author: Fu, Xinmiao title: Simulating and forecasting the cumulative confirmed cases of SARS-CoV-2 in China by Boltzmann function-based regression analyses date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-284376-plwyjhl8.txt cache: ./cache/cord-284376-plwyjhl8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284376-plwyjhl8.txt' === file2bib.sh === id: cord-265005-e6rpryrh author: Tomasello, Elena title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 pages: extension: .txt txt: ./txt/cord-265005-e6rpryrh.txt cache: ./cache/cord-265005-e6rpryrh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265005-e6rpryrh.txt' === file2bib.sh === id: cord-347992-coby2m6e author: Marton, Soledad title: In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date: 2010-06-28 pages: extension: .txt txt: ./txt/cord-347992-coby2m6e.txt cache: ./cache/cord-347992-coby2m6e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347992-coby2m6e.txt' === file2bib.sh === id: cord-350640-sz6xj5o3 author: Menzel, Nicolas title: MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles date: 2012-07-26 pages: extension: .txt txt: ./txt/cord-350640-sz6xj5o3.txt cache: ./cache/cord-350640-sz6xj5o3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350640-sz6xj5o3.txt' === file2bib.sh === id: cord-349358-leicos9j author: Ketzinel‐Gilad, Mali title: RNA interference for antiviral therapy date: 2006-06-16 pages: extension: .txt txt: ./txt/cord-349358-leicos9j.txt cache: ./cache/cord-349358-leicos9j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-349358-leicos9j.txt' === file2bib.sh === id: cord-293857-o8rlqsq5 author: Ghosh, Arun K. title: Organic Carbamates in Drug Design and Medicinal Chemistry date: 2015-01-07 pages: extension: .txt txt: ./txt/cord-293857-o8rlqsq5.txt cache: ./cache/cord-293857-o8rlqsq5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293857-o8rlqsq5.txt' === file2bib.sh === id: cord-344084-z4t2wkgk author: Ellwanger, Joel Henrique title: Beyond HIV infection: neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-344084-z4t2wkgk.txt cache: ./cache/cord-344084-z4t2wkgk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344084-z4t2wkgk.txt' === file2bib.sh === id: cord-324984-ojrpsdt9 author: Ji, Xingyue title: Medicinal chemistry strategies toward host targeting antiviral agents date: 2020-02-14 pages: extension: .txt txt: ./txt/cord-324984-ojrpsdt9.txt cache: ./cache/cord-324984-ojrpsdt9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-324984-ojrpsdt9.txt' === file2bib.sh === id: cord-342901-ca2xxkb2 author: Lloyd, Richard E. title: Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses date: 2015-05-31 pages: extension: .txt txt: ./txt/cord-342901-ca2xxkb2.txt cache: ./cache/cord-342901-ca2xxkb2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342901-ca2xxkb2.txt' === file2bib.sh === id: cord-343963-99rd3o79 author: Wong, Mun-Teng title: Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date: 2014-12-29 pages: extension: .txt txt: ./txt/cord-343963-99rd3o79.txt cache: ./cache/cord-343963-99rd3o79.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343963-99rd3o79.txt' === file2bib.sh === id: cord-006856-b1w25ob5 author: nan title: 19th Meeting of the Austrian Society of Transplantation, Transfusion, and Genetics, October 26–28, 2005 date: 2005 pages: extension: .txt txt: ./txt/cord-006856-b1w25ob5.txt cache: ./cache/cord-006856-b1w25ob5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-006856-b1w25ob5.txt' === file2bib.sh === id: cord-027860-s97hdhh6 author: Zeimet, Anthony title: Infectious Diseases date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-027860-s97hdhh6.txt cache: ./cache/cord-027860-s97hdhh6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-027860-s97hdhh6.txt' === file2bib.sh === id: cord-015372-76xvzvdg author: nan title: National scientific medical meeting 1996 abstracts date: 1996 pages: extension: .txt txt: ./txt/cord-015372-76xvzvdg.txt cache: ./cache/cord-015372-76xvzvdg.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015372-76xvzvdg.txt' === file2bib.sh === id: cord-010088-s9tfvtao author: nan title: Oral Abstracts date: 2013-11-01 pages: extension: .txt txt: ./txt/cord-010088-s9tfvtao.txt cache: ./cache/cord-010088-s9tfvtao.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-010088-s9tfvtao.txt' === file2bib.sh === id: cord-020010-q58x6xb0 author: nan title: 19th ICAR Abstracts: date: 2006-03-13 pages: extension: .txt txt: ./txt/cord-020010-q58x6xb0.txt cache: ./cache/cord-020010-q58x6xb0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-020010-q58x6xb0.txt' === file2bib.sh === id: cord-347710-ff64y6ef author: Wan, Qianya title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-347710-ff64y6ef.txt cache: ./cache/cord-347710-ff64y6ef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-347710-ff64y6ef.txt' === file2bib.sh === id: cord-305085-bv7udg9k author: Lawrence, Robert M. title: Chapter 13 Transmission of Infectious Diseases Through Breast Milk and Breastfeeding date: 2011-12-31 pages: extension: .txt txt: ./txt/cord-305085-bv7udg9k.txt cache: ./cache/cord-305085-bv7udg9k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-305085-bv7udg9k.txt' === file2bib.sh === id: cord-023017-k6edtg58 author: nan title: AASLD Abstracts (pp. 282A–382A) date: 2006-02-10 pages: extension: .txt txt: ./txt/cord-023017-k6edtg58.txt cache: ./cache/cord-023017-k6edtg58.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023017-k6edtg58.txt' === file2bib.sh === id: cord-002774-tpqsjjet author: nan title: Section II: Poster Sessions date: 2017-12-01 pages: extension: .txt txt: ./txt/cord-002774-tpqsjjet.txt cache: ./cache/cord-002774-tpqsjjet.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 20 resourceName b'cord-002774-tpqsjjet.txt' === file2bib.sh === id: cord-007890-bie1veti author: nan title: ECC-4 Abstracts date: 2002-04-16 pages: extension: .txt txt: ./txt/cord-007890-bie1veti.txt cache: ./cache/cord-007890-bie1veti.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-007890-bie1veti.txt' === file2bib.sh === id: cord-000083-3p81yr4n author: nan title: Poster Exhibition date: 2009-01-31 pages: extension: .txt txt: ./txt/cord-000083-3p81yr4n.txt cache: ./cache/cord-000083-3p81yr4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-000083-3p81yr4n.txt' === file2bib.sh === id: cord-023354-f2ciho6o author: nan title: TUESDAY PLENARY SESSION 3 TUESDAY: POSTERS date: 2005-06-08 pages: extension: .txt txt: ./txt/cord-023354-f2ciho6o.txt cache: ./cache/cord-023354-f2ciho6o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 13 resourceName b'cord-023354-f2ciho6o.txt' === file2bib.sh === id: cord-350571-6tapkjb6 author: nan title: 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016 date: 2017-01-10 pages: extension: .txt txt: ./txt/cord-350571-6tapkjb6.txt cache: ./cache/cord-350571-6tapkjb6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-350571-6tapkjb6.txt' === file2bib.sh === id: cord-023346-8sqbqjm1 author: nan title: MONDAY: POSTERS date: 2005-06-08 pages: extension: .txt txt: ./txt/cord-023346-8sqbqjm1.txt cache: ./cache/cord-023346-8sqbqjm1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-023346-8sqbqjm1.txt' === file2bib.sh === id: cord-023364-ut56gczm author: nan title: EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS date: 2005-06-08 pages: extension: .txt txt: ./txt/cord-023364-ut56gczm.txt cache: ./cache/cord-023364-ut56gczm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-023364-ut56gczm.txt' === file2bib.sh === id: cord-009567-osstpum6 author: nan title: Abstracts Oral date: 2008-04-23 pages: extension: .txt txt: ./txt/cord-009567-osstpum6.txt cache: ./cache/cord-009567-osstpum6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-009567-osstpum6.txt' === file2bib.sh === id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 pages: extension: .txt txt: ./txt/cord-022888-dnsdg04n.txt cache: ./cache/cord-022888-dnsdg04n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 17 resourceName b'cord-022888-dnsdg04n.txt' === file2bib.sh === id: cord-010092-uftc8inx author: nan title: Abstract of 29th Regional Congress of the ISBT date: 2019-06-07 pages: extension: .txt txt: ./txt/cord-010092-uftc8inx.txt cache: ./cache/cord-010092-uftc8inx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 17 resourceName b'cord-010092-uftc8inx.txt' === file2bib.sh === id: cord-010119-t1x9gknd author: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 pages: extension: .txt txt: ./txt/cord-010119-t1x9gknd.txt cache: ./cache/cord-010119-t1x9gknd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-010119-t1x9gknd.txt' Que is empty; done keyword-hcv-cord === reduce.pl bib === id = cord-000008-3dgjv0x1 author = Vali, Bahareh title = HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date = 2008-10-20 pages = extension = .txt mime = text/plain words = 5253 sentences = 236 flesch = 47 summary = In response to stimulation with HIV peptide pool, untreated co-infected individuals showed significantly higher frequencies of intra-hepatic CD4 + T-cells producing IFN-c, compared to HCV mono-infected [0.1660.05% vs 0.0260.01%, p,0.05], and HAART-treated co-infected individuals [0.1660.05% vs 0.0360.05%, p,0.05] (Figure 2a ). Therapy naïve co-infected subjects had greater IFN-c producing CD8 + T-cells in response to HIV peptides compared to HCV mono-infected individuals [1.3960.37% vs 0.0260.0%, p,0.05], and HAART was associated with a significant reduction in the frequencies of these cells [1.3960.37% vs 0.3060.26%, p,0.05] (figure 2b). The tetramer cytokine response pattern was shown to be different in the liver compared to blood of the same individual, with diminished intra-hepatic tetramer-specific IFN-c responses and an increase in both CD107a and TNF-a responses, with the majority of SL9 tetramer positive cells expressing these two markers. Therapy naïve co-infected individuals demonstrated a higher frequency of intra-hepatic CD8 + T-cells that produce TNF-a in response to both HCV and HIV antigen stimulation compared to HCV mono-infected individuals. cache = ./cache/cord-000008-3dgjv0x1.txt txt = ./txt/cord-000008-3dgjv0x1.txt === reduce.pl bib === id = cord-003407-f5v3hhr8 author = Hung, Ting-Chun title = Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date = 2018-11-27 pages = extension = .txt mime = text/plain words = 4790 sentences = 203 flesch = 41 summary = Thus, RC's anti-HCV activity appeared strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. Viruses 2018, 10, x FOR PEER REVIEW 6 of 12 strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. To further characterize the mechanism(s) underlying RC's anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. To further characterize the mechanism(s) underlying RC's anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. cache = ./cache/cord-003407-f5v3hhr8.txt txt = ./txt/cord-003407-f5v3hhr8.txt === reduce.pl bib === id = cord-000638-ss1435el author = Beq, Stephanie title = Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date = 2012-04-16 pages = extension = .txt mime = text/plain words = 5142 sentences = 237 flesch = 47 summary = The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. In contrast, Arizcorreta and colleagues showed that IFNa and ribavirin therapy induces a substantial reduction of circulating sjTRECs, in HIV/HCV co-infected patients, accompanied by sustained naïve CD4 + T-cell defect, suggesting thymic dysfunction [10] . While the number of RTEs was similar in HCV-infected patients at study entry and healthy individuals ( These data demonstrate that, as early as one month following treatment initiation, IFNa induces stronger alterations of naïve Tcell subsets, and more specifically in the RTE compartment than in any other T-cell subset, suggesting a specific effect on thymopoiesis. cache = ./cache/cord-000638-ss1435el.txt txt = ./txt/cord-000638-ss1435el.txt === reduce.pl bib === id = cord-000174-mgj9zfft author = Slavenburg, Serena title = Pneumonitis as A Consequence of (Peg)Interferon-Ribavirin Combination Therapy for Hepatitis C: a Review of the Literature date = 2009-04-28 pages = extension = .txt mime = text/plain words = 3198 sentences = 178 flesch = 40 summary = Pulmonary toxicity in patients undergoing HCV combination treatment is rare, and may include interstitial pneumonitis, sarcoidosis, pleuritis, bronchiolitis obliterans organizing pneumonia (BOOP), and exacerbation of asthma [6, 7] . Interstitial pneumonitis occurs only rarely as a side-effect of HCV combination treatment and often leads to discontinuation of therapy, which has great implications for patients. In this article we presented our case of pneumonitis during combination therapy and performed a review in order to generate guidelines to manage symptoms and treatment. In most cases, symptoms of pneumonitis are reversible after cessation of treatment with (peg)interferon and ribavirin, again in support of drug-induced interstitial pneumonitis. Severe interstitial pneumonitis secondary to pegylated interferon alpha-2b and ribavirin treatment of hepatitis C infection Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C. Interstitial pneumonitis during combination therapy with interferon-a and ribavirin in a patient with chronic hepatitis C Interstitial pneumonitis after combination therapy with pegylated interferon alpha-2b and ribavirin for chronic hepatitis C cache = ./cache/cord-000174-mgj9zfft.txt txt = ./txt/cord-000174-mgj9zfft.txt === reduce.pl bib === id = cord-000833-m6abyuvx author = Sekiguchi, Satoshi title = Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date = 2012-12-17 pages = extension = .txt mime = text/plain words = 5915 sentences = 348 flesch = 50 summary = The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. These observations, in addition to the modified histology activity index (HAI) scores, indicated that expression of HCV proteins caused chronic hepatitis in the CN2-29 (+/2) /MxCre (+/2) mice because a weak, though persistent, immune response followed an initial bout of acute hepatitis ( Figure S1 ). To determine whether activation of the host immune response caused the reduction with HCV protein levels in the livers of CN2-29 (+/2) /MxCre (+/2) mice, we used a highly attenuated VV strain, LC16m8, to generate three rVVs [12] . To determine whether rVV-N25 treatment induced the same effect in other strains of HCV transgenic mice, we analyzed RzCN5-15 (+/2) /MxCre (+/2) mice, which express all HCV proteins; in these mice, chronic hepatitis was resolved within 28 days of immunization with rVV-N25. cache = ./cache/cord-000833-m6abyuvx.txt txt = ./txt/cord-000833-m6abyuvx.txt === reduce.pl bib === id = cord-000786-ofpcgxce author = Chua, Brendon Y. title = Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses date = 2012-10-16 pages = extension = .txt mime = text/plain words = 6398 sentences = 293 flesch = 47 summary = Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. Virus-like particles (VLPs) possess features which make them ideal vehicles for the delivery of viral antigens to the immune system; (i) antibody epitopes are presented in the native conformation for induction of potentially neutralising antibodies (ii) multiple T cell, CD4 + and CD8 + , epitopes are packaged in VLPs (iii) VLPs lack regulatory proteins as well as genetic material that could pose a risk of reversion or mutation (iv) encouraging results have been obtained using insect cell-derived recombinant VLPs expressing HCV antigens which induce virus-specific humoral and cellular responses [16] [17] [18] (v) HCV VLPs appear to possess properties favourable for dendritic cell uptake [19] and (vi) they exhibit superior immunogenicity and antigenicity over recombinant protein and DNA-based vaccine approaches [16, 17] . cache = ./cache/cord-000786-ofpcgxce.txt txt = ./txt/cord-000786-ofpcgxce.txt === reduce.pl bib === id = cord-001421-6t5puo6p author = Marfà, Santiago title = Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date = 2014-10-02 pages = extension = .txt mime = text/plain words = 5057 sentences = 229 flesch = 46 summary = The serum proteomic profile and routine liver and renal function tests were initially analyzed in a training set of 10 HCV-RNA recurrent LT patients 6 months post LT that showed a fibrosis stage F$1 at 1 year after LT. HVPG was assessed in 53 of these patients and the average value was of 5.560.8 mm Hg. All the serum samples showed a quite similar expression pattern and coincidences included both the different peptide fragments detected and the signal intensity of these fragments (Data S4). All serum samples included in the test set showed an intensity m/z 5905 peak well below the values found in both healthy subjects and non recurrent HCV patients. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. cache = ./cache/cord-001421-6t5puo6p.txt txt = ./txt/cord-001421-6t5puo6p.txt === reduce.pl bib === id = cord-000830-jiy4cp4n author = Cobo, Fernando title = Application of Molecular Diagnostic Techniques for Viral Testing date = 2012-11-30 pages = extension = .txt mime = text/plain words = 7969 sentences = 385 flesch = 39 summary = The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. The use of amplification techniques such as polymerase chain reaction (PCR), real-time PCR or nucleic acid sequence-based amplification (NASBA) [3] for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range [4, 5] . NASBA assays could identify active infection by detecting viral messenger RNA (mRNA) but the most widely used tests in clinical virus diagnosis are quantitative real-time PCR techniques [8] . Some real-time PCR assays such as LightCycler parvovirus B19 quantitative assay (Roche Diagnostics, Indianapolis, IN) and ABI TaqMan (Applied Biosystems) have been developed for detecting B19 nucleic acids in association with infection during pregnancy or assessing the prevalence of the virus DNA in blood products [62, 63] . cache = ./cache/cord-000830-jiy4cp4n.txt txt = ./txt/cord-000830-jiy4cp4n.txt === reduce.pl bib === id = cord-000473-jpow6iw1 author = Astrovskaya, Irina title = Inferring viral quasispecies spectra from 454 pyrosequencing reads date = 2011-07-28 pages = extension = .txt mime = text/plain words = 5363 sentences = 296 flesch = 54 summary = High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences. Results: In this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Results: In this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Given a collection of 454 pyrosequencing reads generated from a viral sample, reconstruct the quasispecies spectrum, i.e., the set of sequences and the relative frequency of each sequence in the sample population. cache = ./cache/cord-000473-jpow6iw1.txt txt = ./txt/cord-000473-jpow6iw1.txt === reduce.pl bib === id = cord-003158-mhlqnj52 author = Wang, Qi title = Adapted HCV JFH1 variant is capable of accommodating a large foreign gene insert and allows lower level HCV replication and viral production date = 2018-07-13 pages = extension = .txt mime = text/plain words = 5186 sentences = 291 flesch = 56 summary = Previous studies have demonstrated that the HCV JFH1 NS5A C-terminal is a flexible region which is capable of accommodating foreign gene inserts (such as EGFP, 720bp and Rennilla luciferase [Rluc] , 930bp) and still permit HCV replication and viral production (18, 19, (24) (25) (26) (27) (28) (29) . In this study, we used the JFH1-AM120 as a vector to explore if infectious reporter virus would be produced following insertion of LacZ gene that was three time larger than Rluc, into the NS5A C-terminus. This result provided evidence that fusion protein of NS5A and β-galactosidase can be co-expressed in Huh7.5 cells after transfection of JFH1-AM120-LacZ RNA. Our results demonstrate that the LacZ reporter gene can be inserted into the NS5A C-terminus of HCV JFH1-AM120 and will express the predicted NS5A-LacZ fusion protein, which can be detected by western blotting three days after RNA transfection of cells. cache = ./cache/cord-003158-mhlqnj52.txt txt = ./txt/cord-003158-mhlqnj52.txt === reduce.pl bib === id = cord-001834-6xf4o3oy author = Sung, Pil Soo title = Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection date = 2015-10-07 pages = extension = .txt mime = text/plain words = 4039 sentences = 230 flesch = 44 summary = In HCV-infected cells, viral RNA is sensed by retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA-5) in the cytoplasm and Toll-like receptor 3 (TLR3) in the endosome, which leads to downstream signaling that results in the induction of type III and I IFNs and other inflammatory cytokines [28, [36] [37] [38] [39] . Intracellular signals from RIG-I, MDA-5, and TLR3 are transmitted via mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1 receptor domain-containing adaptor inducing IFN- (TRIF), respectively, which leads to the interferon regulatory factor-3 (IRF-3)-dependent induction of IFNs and NF-κB activation in HCV-infected cells [38, 39] . IFN-s activate the same JAK-STAT pathway as type I IFNs [48] [49] [50] , thereby inducing a similar set of ISGs. Although the exact source of IFN-s in HCV-infected liver remains to be clarified, it seems that the production of IFN-s by HCV-infected hepatocytes results in the expression of ISGs, presumably through autocrine and/or paracrine signaling via the IFN-λ receptor [28, [44] [45] [46] . HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons cache = ./cache/cord-001834-6xf4o3oy.txt txt = ./txt/cord-001834-6xf4o3oy.txt === reduce.pl bib === id = cord-006436-61mgtbj4 author = Yoshiba, Makoto title = Development of reliable artificial liver support (ALS)-plasma exchange in combination with hemodiafiltration using high-performance membranes date = 1993 pages = extension = .txt mime = text/plain words = 4449 sentences = 235 flesch = 58 summary = A new artificial liver support system (ALSS) consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) using high-performance membranes of polymethyl metacrylate (PMMA) and cellulose triacetate (CTA) was developed to efficiently remove middle molecules from plasma and treat fulminant hepatic failure (FHF) complicated, by the onset of hepatic coma. It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those, awaiting liver transplantation. Preliminary use of this new ALSS has shown it to be effective in reversing grade V hepatic coma in a patient with fulminant liver failure (15) . A new ALSS system consisting of PE and HDF using high-performance membranes [polymethyl metacrylate (PMMA) and cellulose triacetate (CTA)] was devised to enhance the removal of the middle-Sized molecules thought to be responsible for hepatic coma. cache = ./cache/cord-006436-61mgtbj4.txt txt = ./txt/cord-006436-61mgtbj4.txt === reduce.pl bib === id = cord-006061-z9r5htm9 author = Hu, Bo title = HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation date = 2016-06-17 pages = extension = .txt mime = text/plain words = 4242 sentences = 242 flesch = 53 summary = Altogether, we provide a mechanism by which NS4B induces cell transformation through its PBM, which specifically interacts with the PDZ domains of Scribble and targets Scribble for degradation. Our previous work has shown that NS4B expression activates unfolded protein response (UPR), ER overload response, and NF-κB pathway in human hepatic cells, which could contribute to HCV replication and pathogenesis [11] [12] [13] . As shown in Fig. 5a , expression of HCV NS4B led to reduced USP14 protein levels in both 293T cells and HepG2 cells especially at 48-h post-transfection, indicating that HCV NS4B activates the proteasome-ubiquitin pathway. In this study, we provided a plausible mechanism that NS4B induces cell transformation by degrading the tumor-suppressor protein, Scribble, through the interaction between NS4B PBM and Scribble PDZ domains. The NS4B PBM-Scribble PDZ interaction is important for colony formation of transfected cells, indicating that NS4B PBM contributes to HCV pathogenesis and cellular transformation by inducing Scribble degradation. cache = ./cache/cord-006061-z9r5htm9.txt txt = ./txt/cord-006061-z9r5htm9.txt === reduce.pl bib === id = cord-005617-bxbogskm author = Conway, Anna title = Hepatitis C Screening in Community-Based Voluntary Counselling and Testing Services in Europe: An Observational Study from the COBATEST Network 2014–2018 date = 2019-11-20 pages = extension = .txt mime = text/plain words = 3240 sentences = 146 flesch = 51 summary = This study aims to describe the population being screened for anti-HCV antibodies in the COBATEST Network and identify risk factors associated with a reactive HCV screening test result in the period 2014–2018. This study describes HCV screening activity in CBVCT services, describes the populations being screened, describes the proportion of reactive HCV screening tests and identifies risk factors associated with a reactive HCV screening test result in the COBATEST Network in the years 2014-2018. Secondly, the clients screened for HCV and clients with a reactive screening test were described by socio-demographic characteristics (gender [men, women, transgender], age group [16-24, 25-44, 45-64, > 65], migrants [defined as been born in a country different to the country where the CBVCT service is placed], region of origin), key populations (MSM, PWID, SW) and epidemiological variables (HIV status, HCV screening test results and RNA test results). cache = ./cache/cord-005617-bxbogskm.txt txt = ./txt/cord-005617-bxbogskm.txt === reduce.pl bib === id = cord-006129-5rog0s98 author = Hemida, Maged Gomaa title = Exploiting the Therapeutic Potential of MicroRNAs in Viral Diseases: Expectations and Limitations date = 2012-08-16 pages = extension = .txt mime = text/plain words = 7443 sentences = 508 flesch = 50 summary = [12] Answering back, certain host miRNAs alter the cell gene expression to defend the cells against the viral infection by interfering with viral proteins or other cellular factors as a type of immune response against these particular viruses. [40] These virus-encoded miRNAs play important roles in the establishment of latent infection, as well as the pathogenesis of virally induced diseases. According to the most recent studies, herpesviruses utilize their encoded miRNAs in a wide range of biologic functions, such as inhibition of apoptosis, immune evasion, control of cellular proliferation, and regulation of viral replication. [58] Downregulation of UL114 protein, using miR-UL112-1, results in inhibition of viral DNA replication and subsequently triggers the latent phase of infection, making the virus able to evade the host immune system. cache = ./cache/cord-006129-5rog0s98.txt txt = ./txt/cord-006129-5rog0s98.txt === reduce.pl bib === id = cord-007236-8hiymqyb author = Sun, Ji-Min title = Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway date = 2011-11-09 pages = extension = .txt mime = text/plain words = 4983 sentences = 276 flesch = 47 summary = title: Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway We demonstrated that a group of Monascus orange pigment (MOP) derivatives effectively inhibited NS5B RdRp activity and interfered with the mevalonate synthesis pathway, thereby suppressing HCV replication in cells harbouring an HCV genotype 1b subgenomic replicon and in cells infected with genotype 2a HCV. As shown in Figure 2 (a), among the selected group of MOP AADs that inhibited NS5B RdRp activity in vitro, Lys, Phe, Val, Leu and Ile derivatives also inhibited HCV replication in Huh7 cells, which harbour a HCV subgenomic replicon RNA. Together, these results suggest that in addition to a direct inhibition of NS5B RdRp activity, these MOP AAD compounds also inhibit HCV replication by interfering with the cholesterol biosynthetic pathway downstream of the HMG-CoA reductase step. cache = ./cache/cord-007236-8hiymqyb.txt txt = ./txt/cord-007236-8hiymqyb.txt === reduce.pl bib === id = cord-003993-3bozjfv7 author = Cagliani, Rachele title = Mode and tempo of human hepatitis virus evolution date = 2019-10-25 pages = extension = .txt mime = text/plain words = 7845 sentences = 400 flesch = 40 summary = Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses. This finding, as well as the increasing availability of the genome sequences of human-infecting viruses sampled across different geographic areas, has largely expanded our knowledge about the genetic diversity and evolutionary origin of these human pathogens. Studies that did not account for the TDRP provided estimates of the time to the most recent common ancestor (TMRCA) of HCV genotypes in a range between $200 and 1000 years ago [63, 64, 76, 87, 88] ; the origin of the horse virus was dated around 1800 CE [85] . Although several human hepatitis E cases have a zoonotic origin and orthohepeviruses A are found in diverse mammals, recent data indicated that one or more reverse zoonoses led to the emergence and radiation of HEV genotypes [121] . cache = ./cache/cord-003993-3bozjfv7.txt txt = ./txt/cord-003993-3bozjfv7.txt === reduce.pl bib === id = cord-001848-idmj2d7p author = Onabajo, Olusegun O. title = Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date = 2015-11-01 pages = extension = .txt mime = text/plain words = 7203 sentences = 335 flesch = 47 summary = We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Previously, we showed that transient transfection of an expression construct that generates IFN-l4 protein induced interferon signaling, with activation of interferon-stimulated genes (ISGs) and generation of antiviral response in HepG2, a human hepatoma cell line (Prokunina-Olsson and others 2013). The stable HepG2-ISRE-Luc cells were transfected with corresponding constructs in 96-well plates; untransfected cells were treated with human recombinant interferons-IFNa (2 ng/mL; PBL Assay Science) or custom IFN-l3 (10 ng/ mL). Previously, by performing Western blot analysis, we were unable to detect IFN-l4 in culture media of HepG2 cells transiently transfected with an IFN-l4-producing construct, even though this transfection resulted in strong activation of interferon signaling (Prokunina-Olsson and others 2013). IFN-l4 was detectable in culture media of IFNL4-transfected PHHs and HepG2 cells, but not in corresponding Halo-transfected cells (Fig. 2B) . cache = ./cache/cord-001848-idmj2d7p.txt txt = ./txt/cord-001848-idmj2d7p.txt === reduce.pl bib === id = cord-002410-2zi5iv2t author = Bruening, Janina title = The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy date = 2017-02-01 pages = extension = .txt mime = text/plain words = 6696 sentences = 374 flesch = 44 summary = Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Type III IFNs and ISGs are similarly inducted upon HCV infection of primary human fetal liver cells [98, 99] . In summary, expression of specific IFNL subtypes is induced in PHH and some hepatoma cell lines upon infection with HCV, resulting in limiting virus production. Viral infection and toll-like receptor agonists induce a differential expression of type I and interferons in humans plasmacytoid and monocyte-derived dendritic cells HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons cache = ./cache/cord-002410-2zi5iv2t.txt txt = ./txt/cord-002410-2zi5iv2t.txt === reduce.pl bib === id = cord-007305-pkjfnhro author = Iosub, Silvia title = Leukonychia Partialis in Kawasaki Disease date = 1984-10-17 pages = extension = .txt mime = text/plain words = 1083 sentences = 68 flesch = 57 summary = COLLEAGUES -Some areas in the northern part of the Israel desert (Negev) are known to be endemic for Borrelia recurrentis infection [1] (tick-borne relapsing fever). None of them developed overt symptoms and signs of tick-borne relapsing fever as observed in the subjects from groups I and II. Our patients had nail abnormalities typical for leukonychia partialis of the acquired type, since color changes had not been noted before the present illness and were transient. We would welcome correspondence from others who have seen nail color abnormalities in Kawasaki disease. COLLEAGUES -We examined paired sera from 62 infants with acute non bacterial gastroenteritis and from 50 age-matched controls (admitted to the hospital for nondiarrheal diseases) for antibody to human coronavirus (HCV) OC43 and neonatal-calf diarrhea coronavirus (NCDCY). Convalescent-phase sera from all the patients positive for excretion of coronavirus-like particles in stools, and seronegative for previous HCV OC43 infections, reacted by IEM with HECY-24 and HECV-35 and, to a lesser extent, with HCY OC43. cache = ./cache/cord-007305-pkjfnhro.txt txt = ./txt/cord-007305-pkjfnhro.txt === reduce.pl bib === id = cord-009263-w8bmmgtj author = Colpitts, Che C. title = Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process date = 2020-03-18 pages = extension = .txt mime = text/plain words = 7111 sentences = 385 flesch = 41 summary = The initial binding step primarily involving the lipoprotein component of LVPs likely is a rather unspecific event, which results in the concentration of the virus at the basolateral membrane of hepatocytes and exposure of viral envelope glycoprotein domains that enable the virus to specifically interact with SR-BI, CD81, and CLDN1 (post-binding). Initial attachment of LVPs to hepatocyte basolateral membranes likely involves virus-associated lipoprotein components (particularly apoE [9,13,30-35]), and virus envelope glycoproteins, which interact with highly sulfated heparan sulfate proteoglycans (HSPG) [36] [37] [38] (particularly syndecans [39] [40] [41] ), LDL receptor (LDLR) [42] [43] [44] [45] and SR-BI [46] [47] [48] [49] [50] [51] on the cell surface ( Figure 1 ). Initial attachment of LVPs to hepatocyte basolateral membranes likely involves virus-associated lipoprotein components (particularly apoE [9,13,30-35]), and virus envelope glycoproteins, which interact with highly sulfated heparan sulfate proteoglycans (HSPG) [36] [37] [38] (particularly syndecans [39] [40] [41] ), LDL receptor (LDLR) [42] [43] [44] [45] and SR-BI [46] [47] [48] [49] [50] [51] on the cell surface ( Figure 1 ). cache = ./cache/cord-009263-w8bmmgtj.txt txt = ./txt/cord-009263-w8bmmgtj.txt === reduce.pl bib === id = cord-002369-shk4n8f6 author = Fahmy, Ahmed M. title = The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date = 2017-01-09 pages = extension = .txt mime = text/plain words = 6131 sentences = 355 flesch = 50 summary = The expression of HCV proteins results in the induction of a major rearrangement of host cell membranes, thus leading to the formation of a complex membranous compartment termed the membranous web (MW), which favors viral RNA replication and assembly 3, 4 . To determine whether LC3 or the ATG5-12 conjugate modulates HCV RNA replication, we analyzed the effects of silencing these autophagy genes on viral RNA replication in Huh7 cells stably expressing the JFH1 subgenomic replicon (SGR). Because silencing of LC3 expression led to a clear inhibition of HCV RNA translation after electroporation of the viral RNA but did not significantly affect replication in JFH1-SGR cells, we sought to compare the effect of siRNA treatment before and after infection with HCVcc JFH1 (Fig. 3C) . The autophagy elongation complex proteins (ATG5-12 and ATG16L1) were also detected in the purified MW from NS4B HA replicon cells, but not in the control extract, thus indicating that the elongation complex is indeed present at the HCV replication site. cache = ./cache/cord-002369-shk4n8f6.txt txt = ./txt/cord-002369-shk4n8f6.txt === reduce.pl bib === id = cord-011182-nbtfb39r author = Dehghani, Behzad title = Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran date = 2019-04-20 pages = extension = .txt mime = text/plain words = 6186 sentences = 387 flesch = 55 summary = Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. In this study, we employed several bioinformatics tools to find important mutations in domain 1 of the core protein, general properties of B-cell and T-cell epitopes, modification sites, and structure of domain 1 in Iranian HCV infected samples from 2006 to 2017. (2002 compared sequences of the core protein of Subtype 1b HCV strains obtained from patients with and without HCC and found some amino acid mutation sites (Ogata et al. Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy cache = ./cache/cord-011182-nbtfb39r.txt txt = ./txt/cord-011182-nbtfb39r.txt === reduce.pl bib === id = cord-006856-b1w25ob5 author = nan title = 19th Meeting of the Austrian Society of Transplantation, Transfusion, and Genetics, October 26–28, 2005 date = 2005 pages = extension = .txt mime = text/plain words = 29625 sentences = 1983 flesch = 52 summary = Egr-1 and hypoxia-inducible factor-1 (HIF-1) gene expression was examined in left ventricular biopsies of explanted failing hearts in 28 ICM and 42 DCM patients, as well as in 12 donor grafts before reperfusion (control), at 10, 30, 60 minutes after reperfusion, and at 1, 2, 3, 4, 6, 12 posttransplant weeks, using real-time RT-PCR. The risk of transplant-related mortality (TRM) due to graft-versushost disease (GvHD) is higher in male recipients of female stem cells compared with female patients receiving a graft from a female donor. We therefore analyzed a single-center cohort of 72 high-risk patients transplanted with a related or unrelated stem cell graft after nonmyeloablative conditioning for outcome (acute and chronic GvHD, TRM, relapse, and survival). Four patients between the age of 34 and 44 years underwent allogeneic peripheral blood stem cell (PBSC) transplantation (SCT) from HLA-identical sibling or unrelated donors at our institution. cache = ./cache/cord-006856-b1w25ob5.txt txt = ./txt/cord-006856-b1w25ob5.txt === reduce.pl bib === id = cord-016343-wc3i54fc author = Frese, Michael title = Interferon-Induced Effector Proteins and Hepatitis C Virus Replication date = 2008 pages = extension = .txt mime = text/plain words = 10097 sentences = 503 flesch = 45 summary = RdRp, RNA-dependent RNA polymerase; IRES, internal ribosome entry site; 5BSL3.2, stem loop 3.2 within the coding sequence of NS5B normally result in the production of type I IFNs and the subsequent expression of IFN-induced effector proteins, which in turn would establish an antiviral state in the IFN-producing cell itself and in neighboring cells. Since MxA has the ability to efficiently inhibit a variety of different RNA viruses, MxA was the first IFN-induced effector protein to be analyzed for its antiviral activity in the HCV replicon system (Frese et al., 2001) . Rather indirect evidence that the OAS/RNase L pathway may indeed target HCV replication/translation was recently provided by Taguchi and co-workers, who reported that the N-terminal portion of NS5A (amino acids 1 to 148), which lacks the so-called PKR-binding domain, binds to OAS proteins and there by counteract the antiviral activity of IFN-α (Taguchi et al., 2004) . cache = ./cache/cord-016343-wc3i54fc.txt txt = ./txt/cord-016343-wc3i54fc.txt === reduce.pl bib === id = cord-015372-76xvzvdg author = nan title = National scientific medical meeting 1996 abstracts date = 1996 pages = extension = .txt mime = text/plain words = 36596 sentences = 2204 flesch = 53 summary = One, two and five-year survival rates were examined; age at diagnosis and lesion type were extremely significant factors in relation to patient outcome. Patients' age, sex, risk group, CDC stage, CD4 count, indication for therapy, complication rate and response to treatment are described. Fifty-eight patients (34 male, 24 female) ranging in age from 15 to 65 years (Mean + SD = 28.4 + 10.8) were included in the study. Among these 48 patients (mean age 68.0+12.7), after controlling for age and for the duration and continuity of subsequent antipsychotic treatment, increasing duration of initially untreated psychosis was associated with greater severity of negative symptoms (p<0.005) and with lower scores on the MMSE (p<0.05) but not with executive dysfunction on the EXIT (p=0.3). Conclusion Although not a population based study, care of IDDM in Ireland is almost totally hospital clinic based Cigarette smoking is identified as the major problem to be addressed Patients with diabetes meltitus (DM) are at a higher risk of developing vascular complications, including coronary artery disease (CAD). cache = ./cache/cord-015372-76xvzvdg.txt txt = ./txt/cord-015372-76xvzvdg.txt === reduce.pl bib === id = cord-017506-t86v3zw3 author = Knox, Tamsin A. title = Alcohol, HIV/AIDS, and Liver Disease date = 2012-04-27 pages = extension = .txt mime = text/plain words = 7643 sentences = 353 flesch = 37 summary = Cardiovascular disease is likely due to a combination of additional risk factors found in HIV infection [ 26 ] including (1) chronic in fl ammation from HIV viral replication and subsequent immunode fi ciency [ 134 ] , (2) the effect of chronic in fl ammation on serum lipid levels [ 133 ] , (3) the metabolic effects of certain classes of antiretroviral medications [ 131, 133 ] , (4) increased prevalence of insulin resistance [ 135 ] , and (5) increased translocation of bacteria across the small intestine into the bloodstream as a result of immunode fi ciency [ 136 ] . Freiberg et al., studying the VACS Cohort, found that the risk of cardiovascular disease was increased (OR 1.55, 95% CI 1.07-2.23) in HIV-infected men with alcohol abuse or dependence, when controlled for cardiac risk factors, ART use, and CD4 count [ 8 ] . cache = ./cache/cord-017506-t86v3zw3.txt txt = ./txt/cord-017506-t86v3zw3.txt === reduce.pl bib === id = cord-018220-8m11ig06 author = Duncan, Coley B. title = Viral Infections date = 2009-02-02 pages = extension = .txt mime = text/plain words = 6477 sentences = 324 flesch = 45 summary = The recommendations of the Advisory Committee on Immunization Practices (ACIP) 2007 relating to the elderly, include vaccination of all persons ³ 50 years, vaccination of residents of nursing homes and chronic-care facilities, vaccination of healthcare personnel, and vaccination of healthy household contacts (including children) and caregivers of adults ³ 50 years (3) . In a prospective study from Rochester, NY, using a combination of viral culture, RT-PCR and serology for diagnosis, RSV infection was documented in 3-7% of 608 healthy elderly and 4-10% of adults with chronic cardiopulmonary conditions over four winter seasons (16) . In healthy elderly patients and in adults with chronic pulmonary disease, low serum neutralizing antibody titers are associated with increased risk of hospitalization with RSV infection suggesting a vaccine may be beneficial. Although PIV infections are not commonly documented in older adults, several studies of community-acquired pneumonia and chronic obstructive pulmonary disease (COPD) exacerbations implicate PIV as a cause in 2-17% of cases (25, 26) . cache = ./cache/cord-018220-8m11ig06.txt txt = ./txt/cord-018220-8m11ig06.txt === reduce.pl bib === id = cord-013244-d6saaiu9 author = Eijsink, Job F. H. title = Cost-effectiveness of hepatitis C virus screening, and subsequent monitoring or treatment among pregnant women in the Netherlands date = 2020-10-16 pages = extension = .txt mime = text/plain words = 5915 sentences = 310 flesch = 51 summary = However, it is conceivable that in the near future DAA treatment of HCV-infected women during pregnancy becomes available, not only to limit disease progression in the patient, but also to prevent vertical transmission of the virus to the child. A screening model linked to HCV-disease states within a Markov model was used to evaluate the cost-effectiveness (CE) of HCV screening of pregnant women, with initial treatment during pregnancy, compared to current practice (no screening and no intervention) from a health-care payer perspective in the Netherlands. We subsequently determined the cost-effectiveness and budget impact of HCV screening and treatment among the four cohorts of pregnant women following the different scenarios and comparisons. Our present study demonstrates that HCV screening of pregnant women and subsequent immediate treatment of all HCV-positive individuals with DAAs is a cost-effective intervention in the Netherlands. cache = ./cache/cord-013244-d6saaiu9.txt txt = ./txt/cord-013244-d6saaiu9.txt === reduce.pl bib === id = cord-002774-tpqsjjet author = nan title = Section II: Poster Sessions date = 2017-12-01 pages = extension = .txt mime = text/plain words = 83515 sentences = 5162 flesch = 54 summary = Results: The CHIP Framework The CHIP framework aims to improve the health and wellness of the urban communities served by St. Josephs Health Centre through four intersecting pillars: • Raising Community Voices provides an infrastructure and process that supports community stakeholder input into health care service planning, decision-making, and delivery by the hospital and across the continuum of care; • Sharing Reciprocal Capacity promotes healthy communities through the sharing of our intellectual and physical capacity with our community partners; • Cultivating Integration Initiatives facilitates vertical, horizontal, and intersectoral integration initiatives in support of community-identified needs and gaps; and • Facilitating Healthy Exchange develops best practices in community integration through community-based research, and facilitates community voice in informing public policy. cache = ./cache/cord-002774-tpqsjjet.txt txt = ./txt/cord-002774-tpqsjjet.txt === reduce.pl bib === id = cord-010273-0c56x9f5 author = Simmonds, Peter title = Virology of hepatitis C virus date = 2001-10-10 pages = extension = .txt mime = text/plain words = 7897 sentences = 337 flesch = 41 summary = 1,2 The identification of HCV led to the development of diagnostic assays for infection, based either on detection of antibody to recombinant polypeptides expressed from cloned HCV sequences or direct detection of virus ribonucleic acid (RNA) sequences by polymerase chain reaction (PCR) using primers complimentary to the HCV genome. 6 '13 Remarkably, a series of plant viruses that are structurally distinct from each of the mammalian virus groups, and with different genome organizations, have RNA-dependent RNA polymerase amino acid sequences that are perhaps more similar to those of HCV than are the flaviviruses. In contrast to the highly restricted sequence diversity of the 5'NCR and adjacent core region, the two putative envelope genes are highly divergent between different variants of HCV (Table III) 111-114 and show a three-to-four-times higher rate of sequence change with time in persistently infected patients, ll5 Because these proteins are likely to lie on the outside of the virus, they would be the principal targets of the humoral immune response to HCV elicited on infection. cache = ./cache/cord-010273-0c56x9f5.txt txt = ./txt/cord-010273-0c56x9f5.txt === reduce.pl bib === id = cord-010088-s9tfvtao author = nan title = Oral Abstracts date = 2013-11-01 pages = extension = .txt mime = text/plain words = 43522 sentences = 2257 flesch = 49 summary = These include 'incorrect blood component transfused' events, where the blood component was intended for another recipient (frequently due to errors in patient identification at the time of collection of the pre-transfusion sample, or at the time of bedside administration), or did not meet the patient's special needs (such as a patient with a red cell antibody who did not receive the required antigen-negative unit). Methods: Eligibility criteria for inclusion in the study included the following: transfusion of Rh D positive platelets, no anti D detectable before transfusion, no previous exposure to Rh D positive blood components, and results of follow-up testing of anti-D in patients serum available. In addition, the allelic frequency of Hpdel was calculated to be 0.015 by a genetic study of a limited number of the Japanese individuals, suggesting that Hp deficiency might distribute among the Japanese population as a phenotype of serum Hp. Aims: In this report, we present the results obtained from a hemovigilance survey carried out between 1998 and 2012, in which Hp deficiency was identified among Japanese patients who had experienced nonhemolytic TRs (NHTRs), and those obtained from a screening of Hp-deficient Japanese healthy blood donors. cache = ./cache/cord-010088-s9tfvtao.txt txt = ./txt/cord-010088-s9tfvtao.txt === reduce.pl bib === id = cord-011026-iapgkz0p author = El-Bitar, Alaa M. H. title = Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus date = 2019-07-06 pages = extension = .txt mime = text/plain words = 5247 sentences = 296 flesch = 53 summary = title: Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). For dengue virus infectivity, serially diluted venom fractions and Smp76 were mixed with fixed amount of DENV and incubated for 2 h at 37 °C. The above results suggest that the Smp76 directly affects HCV particles and/or host cells in the culture medium to inhibit the viral infection and does not have an antiviral effect in the cells. To determine whether the antiviral activity of Smp76 peptide (previously described) was specific to HCV and DENV, a Schematic of infection assay. The exact mechanism by which Smp76 exerts its antiviral activity against HCV and DENV to inhibit infecting their target cells need further studies. cache = ./cache/cord-011026-iapgkz0p.txt txt = ./txt/cord-011026-iapgkz0p.txt === reduce.pl bib === id = cord-026112-58sa5z03 author = Dehghani-Dehej, Farzaneh title = Prevalence of HCV and/or HBV coinfection in Iranian HIV-infected patients date = 2020-04-24 pages = extension = .txt mime = text/plain words = 4005 sentences = 198 flesch = 47 summary = This study aimed to investigate molecular epidemiology of HBV and HCV coinfection in Iranian HIV-infected individuals. Materials & methods: In this cross-sectional study, serological markers of HBV and HCV infection (hepatitis B surface antigen [HBsAg], hepatitis B e-antigen [HBeAg], hepatitis B e-antibody [HBeAb] and hepatitis B core antibody [HBcAb]) and anti-HCV antibodies [anti-HCV Abs] were tested in 198 Iranian HIV-infected patients. HIV/HBV-coinfected people have a higher rate of progression to liver fibrosis, cirrhosis, HCC, less clearance of HBsAg and occult HBV infections (OBI) are more frequent in these patients [13] . The aim for this study is to investigate the prevalence of HCV and/or HBV coinfection in Iranian HIV-infected individuals. According to a previous study, prevalence of cirrhosis in HIV/HBV/HCV triple-infected patients was higher than HIV/HBV-or HIV/HCV-coinfected individuals [57] . cache = ./cache/cord-026112-58sa5z03.txt txt = ./txt/cord-026112-58sa5z03.txt === reduce.pl bib === id = cord-030361-0tepkjdl author = Mohammed Abdul, Mubeen Khan title = Hepatitis C Virus in the Elderly in the Direct-Acting Antiviral Era: from Diagnosis to Cure date = 2020-08-11 pages = extension = .txt mime = text/plain words = 4991 sentences = 233 flesch = 42 summary = In a study conducted by Foster and colleagues, data was combined from nine phase 2 and phase 3 clinical trials to evaluate efficacy and safety outcomes in HCV patients ≥ 65 years old treated with the pan-genotypic regimen, glecaprevir/pibrentasvir, for 8, 12, or 16 weeks [28] . Shiffman and colleagues reported outcomes of 123 patients aged 65 years or older enrolled in three phase 3 studies who received sofosbuvir/velpatasvir, a pan-genotypic DAA, for 12 weeks for the treatment of chronic HCV [29] . Safety and efficacy of sofosbuvir/ velpatasvir for the treatment of chronic hepatitis C in patients aged 65 years or older: a retrospective analysis of phase 3 studies The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection cache = ./cache/cord-030361-0tepkjdl.txt txt = ./txt/cord-030361-0tepkjdl.txt === reduce.pl bib === id = cord-018785-tcr5xlf8 author = Nambiar, Puja title = Infection in Kidney Transplantation date = 2018-06-27 pages = extension = .txt mime = text/plain words = 9364 sentences = 506 flesch = 36 summary = The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. The risk factors for development of CMV disease include donor seropositivity/recipient seronegativity(Dþ/RÀ), use of induction immunosuppression (antilymphocyte antibodies), donor age >60 years, simultaneous kidney-pancreas transplantation, treatment for acute rejection, impaired transplant function, and concurrent infection from other viruses (like EBV and HHV-6 and 7) (De Keyzer et al. The risk factors for PTLD include EBV naïve recipients who receive EBV seropositive organs, active primary EBV infection, younger recipient, coinfection by CMV and other viruses, prior splenectomy, second transplant, acute or chronic graft versus host disease, immunosuppressive drug regimen (OKT3 or polyclonal antilymphocyte antibody), and the type of organ transplanted. cache = ./cache/cord-018785-tcr5xlf8.txt txt = ./txt/cord-018785-tcr5xlf8.txt === reduce.pl bib === id = cord-013176-6ckuya1w author = Ninfali, Paolino title = Antiviral Properties of Flavonoids and Delivery Strategies date = 2020-08-21 pages = extension = .txt mime = text/plain words = 8102 sentences = 372 flesch = 35 summary = Quercetin, extracted from Embelia ribes (Mirsinaceae), exhibited antiviral effects against HCV, exerted through activity inhibition of the viral protease Non-Structural protein 3 (NS3), leading to a decrease in HCV replication [36] . The natural extract of Tetrastigma hemsleyanum (Vitaceae) contains many flavonoids, including vitexin, vitexin-2-O-rhamnoside, isorhamnetin, rutin, kaempferol, astragalin, quercitrin, quercetin and iso-quercetin, which were shown to be able to exert anti-influenza virus activity, with different efficiency, through the reduction of the number of plaques induced by the influenza virus in infected Madin-Darby Canine Kidney (MDCK) cells [21] . In future perspective, this approach could be considered in order to possibly improve the antiviral activity of some flavonoids, like baicalin, that was able, like fludarabine [65] , to act against HIV-1 chronic infection of human monocytes and macrophages, inhibiting the fusion of HIV virus envelope proteins with these cells [73] . cache = ./cache/cord-013176-6ckuya1w.txt txt = ./txt/cord-013176-6ckuya1w.txt === reduce.pl bib === id = cord-258234-qn8xp4v9 author = Striker, Rob title = Inhibitors of Peptidyl Proline Isomerases As Antivirals in Hepatitis C and Other Viruses date = 2014-11-06 pages = extension = .txt mime = text/plain words = 2485 sentences = 132 flesch = 38 summary = Cyclophilin inhibitors that reduce viral replication also block interactions between cyclophilin A and NS5A, suggesting that this association is important during the viral life cycle and might be the relevant target of the antiviral activity of cyclosporine [11] [12] [13] . HCV NS5A is a protein that is rich in both proline residues and disorder and that associates with cyclophilin A via domain 2. However, these regions share several common properties: the flexible cyclophilin-interacting loop in CA is also bracketed by prolines, just as the PAWARPDYNP motif in HCV; residues 86, 91, and 96 that surround the glycine-proline in CA influence viral susceptibility to cyclophillin inhibitors similar to mutations surrounding NS5A P319 [25] ; and the critical glycine-proline is amino-terminal to regions of CA that are actually more proline rich and predicted by bioinformatics analysis to be disordered, analogous to the positioning of the PAWARPDYNP motif in HCV NS5A. cache = ./cache/cord-258234-qn8xp4v9.txt txt = ./txt/cord-258234-qn8xp4v9.txt === reduce.pl bib === id = cord-264713-38dlh3wg author = Vernet, Guy title = Molecular diagnostics in virology date = 2004-08-20 pages = extension = .txt mime = text/plain words = 4798 sentences = 233 flesch = 42 summary = Viral load and antiviral resistance or subtyping assays are now part of the biological monitoring of patients chronically infected by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV. The most striking illustration of the power of molecular techniques concerns blood transmitted viruses-human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) for which spectacular progresses in the detection and treatment of viral diseases have been made following the introduction of qualitative and quantitative nucleic acid tests (NAT). For example, we have observed, using a DNA-microarray assay (see below), that the analytical sensitivity of multiplex RT-PCR detection of six viruses, i.e. influenza A, influenza B, RSV A/B, parainfluenza 1, 2 and 3 is reduced by a factor of <1-2 logs compared to single detections, depending on the virus. cache = ./cache/cord-264713-38dlh3wg.txt txt = ./txt/cord-264713-38dlh3wg.txt === reduce.pl bib === id = cord-253768-y35m3vh1 author = Springer, Sandra A title = Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA’s Advocacy Agenda date = 2020-10-01 pages = extension = .txt mime = text/plain words = 5844 sentences = 262 flesch = 41 summary = Nevertheless, a number of barriers to care in people who use drugs need to be addressed to end the opioid and HIV epidemics in the United States as well as reduce the other infectious disease health outcomes. To address these barriers we recommend expanding Medicaid, expanding access to harm reduction services, improving treatment and surveillance to enhance the continuum of care, and treating opioid and other substance use disorders (SUD), including through lowbarrier hospital and community-based treatment, as well as in the criminal justice setting. Increased state and federal funding are needed to expand SSP and other harm reduction services, including access to MOUD and infectious diseases treatment services in order to decrease HCV, HIV, IDU-related infections, and vaccine-preventable diseases, and improve OUD-related outcomes [26, 27] . cache = ./cache/cord-253768-y35m3vh1.txt txt = ./txt/cord-253768-y35m3vh1.txt === reduce.pl bib === id = cord-261287-l4649du3 author = Puoti, Massimo title = A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients() date = 2004-05-06 pages = extension = .txt mime = text/plain words = 3674 sentences = 151 flesch = 43 summary = However, a cumulative sustained virological response (SVR) was observed in only 22% (95% Confidence interval (CI), 14 -30%) of 111 patients enrolled in four pilot uncontrolled studies aiming to assess the efficacy and tolerability of ribavirin plus interferon alfa1 administered thrice weekly in HIV/HCV co-infected patients [4 -7] . In order to establish that the SVR in the triple therapy arm is at least three times higher than the 18% sustained response rate observed in HIV-co-infected patients treated with interferon and ribavirin in pilot studies [4] [5] [6] [7] , it was calculated that at least 64 patients should have been enrolled. In conclusion, intensification of interferon alpha schedule and amantadine addition do not appear to improve the limited efficacy of standard combination therapy including interferon thrice weekly plus ribavirin for the treatment of chronic hepatitis C in HIV-co-infected patients. cache = ./cache/cord-261287-l4649du3.txt txt = ./txt/cord-261287-l4649du3.txt === reduce.pl bib === id = cord-255781-55zrmgxq author = Bergman, Scott J. title = Interferons as Therapeutic Agents for Infectious Diseases date = 2011-12-31 pages = extension = .txt mime = text/plain words = 6408 sentences = 376 flesch = 44 summary = These agents consist of naturally occurring small proteins with molecular weights of 15,000 to 27,600 Da. 3 Each is considered a first-line option for the treatment of chronic hepatitis C virus (HCV) infection in combination with ribavirin. Along with the list of additional indications approved by the Food and Drug Administration shown in Table 1 , IFN-a was shown to be an effective treatment for the symptoms of an aggressive case of chronic active Epstein-Barr virus, but did not eliminate infection entirely. IFNs have been tested repeatedly against infectious diseases, but injections are used mostly for the treatment of viral hepatitis C and prevention of infections in patients with chronic granulomatous disease clinically. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection cache = ./cache/cord-255781-55zrmgxq.txt txt = ./txt/cord-255781-55zrmgxq.txt === reduce.pl bib === id = cord-284904-qw1ig2v4 author = Mizui, Tomokazu title = Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy date = 2009-09-17 pages = extension = .txt mime = text/plain words = 4099 sentences = 250 flesch = 49 summary = In this study, we investigated the role of autophagy on hepatitis C virus (HCV) RNA replication and demonstrated anti-HCV effects of an autophagic proteolysis inhibitor, chloroquine. Inhibition of autophagy and replication of HCV replicon Cells were treated with 3-methyladenine (10 mM) or mixture of E64d (1 lg/ml) and pepstatin A (1 lg/ml), chloroquine (10 -7 -10 -3 M), interferon (IFN)a (100 U/ml) for 18 h, the levels of replication of HCV replicon were assessed by luciferase assay. To clarify the role of autophagy on the replication of HCV, Huh7/ Rep-Feo cells were treated with 3-methyladenine (10 mM) or a mixture of E64d (10 lg/ml) and pepstatin A (10 lg/ml) which inhibited autophagic protein degradation. Anti-HCV effect of chloroquine independent of IFN signaling pathway IFN-inducible double-stranded RNA-activated protein kinase R (PKR) plays a key antiviral role against hepatitis C virus [26, 27] . cache = ./cache/cord-284904-qw1ig2v4.txt txt = ./txt/cord-284904-qw1ig2v4.txt === reduce.pl bib === id = cord-264936-3posyr5n author = Mohammadzadeh, Sara title = Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications date = 2014-11-24 pages = extension = .txt mime = text/plain words = 6202 sentences = 292 flesch = 49 summary = RESULTS: The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of "GGTAAG" splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). In this study, we aimed to: i) Construct an efficient transient tobacco expression system for HCVcp N-121 by designing a highly codon-optimized gene and employment of the Iranian Jafarabadi-tobacco plant cultivar which is a high biomass producer ii) Evaluate the expression level of HCVcp for a potato virus X-based vector (PVX) (32) com-pared to a classic pBI121 binary plant vector in co-agroinfiltration with P19 gene silencing suppressor plasmid and iii) Assess the antigenicity of this tobacco-derived HCVcp for potential clinical (diagnostic and vaccine formulation) applications. cache = ./cache/cord-264936-3posyr5n.txt txt = ./txt/cord-264936-3posyr5n.txt === reduce.pl bib === id = cord-015941-4fz79wzf author = Hu, Yuan title = Molecular Techniques for Blood and Blood Product Screening date = 2018-11-10 pages = extension = .txt mime = text/plain words = 7210 sentences = 381 flesch = 50 summary = Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus's genetic material instead of waiting for the body's response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [21] , thus further improving blood safety. One reason for this is that currently available blood screening technologies detect core antibodies or surface antigens, which appear up to 8 weeks after infection. The anti-HBc test developed in 1987 detects an antibody to the hepatitis B virus that is produced during and after infection. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing cache = ./cache/cord-015941-4fz79wzf.txt txt = ./txt/cord-015941-4fz79wzf.txt === reduce.pl bib === id = cord-017764-h1w9gbxk author = Meanwell, Nicholas A. title = The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex date = 2018-06-08 pages = extension = .txt mime = text/plain words = 9250 sentences = 389 flesch = 39 summary = A groundbreaking clinical trial that combined daclatasvir (1) with the protease inhibitor asunaprevir (52) established that a chronic HCV infection could be cured with small molecule therapy in the absence of immune stimulation, setting the stage for approval of this regimen for the treatment of GT-1b-infected subjects by the Japanese health authorities on July 4, 2014. The discovery of the hepatitis C virus (HCV) nonstructural 5A (NS5A) replication complex inhibitor daclatasvir (1) began with the development of a genotype 1b (GT-1b) replicon that was implemented as a phenotypic screen using a design that conferred a stringent triaging of hit molecules [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] . A screen of compounds selected from the library of HCV NS5A inhibitors assessed in the presence of 1 using the Tyr93Asn GT-1aresistant replicon, followed by SAR optimization, identified Syn-395 (52) as a molecule capable of restoring the sensitivity of resistant virus to the inhibitory effects of 1. Discovery of daclatasvir, a pan-genotypic hepatitis C virus NS5A replication complex inhibitor with potent clinical effect cache = ./cache/cord-017764-h1w9gbxk.txt txt = ./txt/cord-017764-h1w9gbxk.txt === reduce.pl bib === id = cord-023017-k6edtg58 author = nan title = AASLD Abstracts (pp. 282A–382A) date = 2006-02-10 pages = extension = .txt mime = text/plain words = 65796 sentences = 3553 flesch = 51 summary = 14/55 (25%) patients in AC who did not discontinue by week 24 received ribavirin dose reduction in comparison to 31/108 ( The clinical outcome in response to combination therapy for treatment of chronic hepatitis C virus (HCV) infection appears to be different for Caucasian versus African American patients. Over the period of combination therapy, most patients in which serum virus titers were reduced to non detectable levels had significant increases in T cell responses to HCV proteins. CHRONIC Background: Recent large prospective trials demonstrated that the combination therapy of interferon (1FN)-alphalribavirin significantly increased the ratio of a sustained virological response in patients with chronic hepatitis C in comparison with IFN monotherapy, especially in patients with high HCV-RNA titer and genotype lb. Results: Patients with chronic HCV infection showed higher MxA gene expression levels than healthy controls, indicating that hepatitis C virus induces IFN production. cache = ./cache/cord-023017-k6edtg58.txt txt = ./txt/cord-023017-k6edtg58.txt === reduce.pl bib === id = cord-005138-u2lwgyyf author = Kou, Yi-Hen title = Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A date = 2006-08-23 pages = extension = .txt mime = text/plain words = 6110 sentences = 363 flesch = 51 summary = title: Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A In this study, we have demonstrated that NS4A specifically interacted with eukaryotic elongation factor 1A (eEF1A) and inhibited both cap-and HCV IRES-dependent protein synthesis. To perform translation inhibition assay in culture cells, plasmids encoding V5-tagged HCV nonstructure proteins NS3, NS4A, NS4B, and NS4A mutants were independently cotransfected with the cap-dependent monocistronic luciferase reporter pCMV-Luc or the bicistronic luciferase reporter pJSS12 into Huh7 cells. To perform cap-dependent in-vitro-translation inhibition assay, GST and GST-NS4A fusion proteins that were recovered from the Sepharose 4B beads as described earlier were preincubated with 5 ll of rabbit reticulocyte lysate (RRL, Promega) at 4°C for 1 h. The results demonstrated that both NS4A and NS4B inhibited HCV IRES-mediated translation to levels similar to those of the cap-dependent translation, whereas no effect was detected with the viral NS3 protein (Figure 2d ). cache = ./cache/cord-005138-u2lwgyyf.txt txt = ./txt/cord-005138-u2lwgyyf.txt === reduce.pl bib === id = cord-020010-q58x6xb0 author = nan title = 19th ICAR Abstracts: date = 2006-03-13 pages = extension = .txt mime = text/plain words = 46663 sentences = 2181 flesch = 44 summary = In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. cache = ./cache/cord-020010-q58x6xb0.txt txt = ./txt/cord-020010-q58x6xb0.txt === reduce.pl bib === id = cord-253825-d9borky8 author = Blaising, Julie title = Arbidol as a broad-spectrum antiviral: An update date = 2014-04-24 pages = extension = .txt mime = text/plain words = 8757 sentences = 431 flesch = 44 summary = ARB has been shown to display antiviral in vitro and/or in vivo activity against a number of enveloped or non-enveloped RNA or DNA viruses, including influenza viruses A, B and C , respiratory syncytial virus, SARS-CoV, adenovirus, parainfluenza type 5, poliovirus 1, rhinovirus 14, coxsackievirus B5, hantaan virus, Chikungunya virus, HBV and HCV [reviewed in Boriskin et al. Shi and coworkers showed a greater inhibitory effect on influenza A H1N1 when ARB was added before infection or when it was pre-incubated with the virus (Shi et al., 2007) , suggesting that membrane impregnation and/or metabolites could underlie ARB antiviral activity (see Section 6.). Recently, Tannock and coworkers reported a potent antiviral activity of ARB on several virus families responsible of respiratory infections in animals and humans, in particular on influenza A H3N2 (IC50 12 lM), and the non-enveloped Picornaviridae poliovirus 1 and rhinovirus 14 (Brooks et al., 2012 ; see also Brooks et al., 2004) . cache = ./cache/cord-253825-d9borky8.txt txt = ./txt/cord-253825-d9borky8.txt === reduce.pl bib === id = cord-256036-gd53s4dv author = Sandmann, Lisa title = Barriers of hepatitis C virus interspecies transmission date = 2013-01-01 pages = extension = .txt mime = text/plain words = 7894 sentences = 373 flesch = 40 summary = In contrast to human hepatocytes, murine cells do not support HCV entry thereby creating a first and important barrier for a broader host tropism of the virus. Utilizing blocking antibodies specific to CD81 or the viral envelope protein E2, expression of entry factor mutants and mice with a targeted disruption of the SCARB1 gene validated uptake of HCV into murine hepatocytes in an HCV glycoprotein-mediated fashion. Taking advantage of the high mutational plasticity of HCV, three adaptive mutations in the viral glycoproteins E1 and E2 were identified that allowed the virus to enter cells expressing human SCARB1, CLDN1, OCLN and mouse CD81. Recently, a genetically humanized mouse model was constructed utilizing cell culture produced recombinant hepatitis C virus to activate a cellular encoded reporter (Dorner et al., 2011, in press ). Human occludin is a hepatitis C virus entry factor required for infection of mouse cells A humanized mouse model to study Hepatitis C virus infection, immune response, and liver disease cache = ./cache/cord-256036-gd53s4dv.txt txt = ./txt/cord-256036-gd53s4dv.txt === reduce.pl bib === id = cord-281389-sht0yx4a author = Tal, Michal Caspi title = Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date = 2020-06-23 pages = extension = .txt mime = text/plain words = 7629 sentences = 382 flesch = 46 summary = Examination of a publicly available gene expression data set (Gene Expression Omnibus [GEO] accession number GSE147507) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of A549 human lung cells also showed a significant upregulation of CD47 compared to mock-infected controls (Fig. 1D ). Multiple PBMC subsets showed significantly upregulated CD47 expression in response to Borrelia burgdorferi infection compared to naive cells (Fig. 1E) . Overall, the combined in vivo and in vitro results from multiple pathogen infections in both human and mouse cells indicated that the upregulation of CD47 was a conserved host response possibly related to host sensing mechanisms. Compared to healthy controls, monocytes and DCs from HCV patients demonstrated a sustained upregulation of CD47 at all treatment time points, including the 6-month posttreatment time point ( Fig. 3B (B) CD47 MFI on human total PBMCs from 4 separate donors stimulated with titrated concentrations of R848 from 0.1 g/ml to 10 g/ml, as indicated, for 48 h. cache = ./cache/cord-281389-sht0yx4a.txt txt = ./txt/cord-281389-sht0yx4a.txt === reduce.pl bib === id = cord-024003-698d15gk author = Loutfy, Samah A title = Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines date = 2020-04-22 pages = extension = .txt mime = text/plain words = 6596 sentences = 316 flesch = 49 summary = This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. 17, 19 Previously, chitosan nanoparticles (CsNPs) have been conjugated with antiretroviral agents like saquinavir, a protease inhibitor, to improve anti-HIV therapy; cell targeting efficiency increased by 92% compared to the soluble drug control. Antiviral activities of curcumin, CsNPs and CuCs nanocomposite were tested against the viral entry in infected Huh7 cells from positive HCV-4a patients through mixing of equal volumes of the nontoxic concentrations of the investigated materials and viral titer; in this assay one viral titer was involved (10 5 IU/mL). The HCV core protein expression level post-treatment of HCV infected Huh7 cells with curcumin, CsNPs, and CuCs nanocomposite against viral replication and entry was quantified in relation to β-actin as a control ( Table 7 , Figure 8 ). cache = ./cache/cord-024003-698d15gk.txt txt = ./txt/cord-024003-698d15gk.txt === reduce.pl bib === id = cord-265588-1tcaleeo author = Yousaf, Tahir title = Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus date = 2018-03-20 pages = extension = .txt mime = text/plain words = 3480 sentences = 209 flesch = 55 summary = title: Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus Therefore, this study was designed to find out phytochemicals and investigate antiviral activity of methanol extract of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus (HCV infection). Antiviral activity of the selected plant extract was find out against HCV infected HepG2 cells. Phytochemical analysis showed the presence of flavonoids and phenols in all plant extracts while amino acids, alkaloids and tannins were present in B. So, it was important to find out the toxic effects of four medicinal plants used in the current study before evaluating for anti-HCV activities. Antiviral activities of methanol extract of four medicinal plants were tested against HCV and results has been summarized in Fig. 2 for 24 h and Fig. 3 for 48 h treatments. cache = ./cache/cord-265588-1tcaleeo.txt txt = ./txt/cord-265588-1tcaleeo.txt === reduce.pl bib === id = cord-017948-fqhl1qb4 author = Hu, Yuan title = Molecular Techniques for Blood and Blood Product Screening date = 2012-04-05 pages = extension = .txt mime = text/plain words = 7304 sentences = 372 flesch = 54 summary = Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus's genetic material instead of waiting for the body's response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [ 19 ] , thus further improving blood safety. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-ampli fi cation testing cache = ./cache/cord-017948-fqhl1qb4.txt txt = ./txt/cord-017948-fqhl1qb4.txt === reduce.pl bib === === reduce.pl bib === id = cord-264326-teahway7 author = Eleftheriou, Phaedra title = In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus date = 2020-05-29 pages = extension = .txt mime = text/plain words = 5403 sentences = 256 flesch = 50 summary = According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since the 3D structure of the active site of the enzyme is crucial for catalytic activity, we proceeded to a comparison of the SARS-CoV-2 main protease, Mpro, with the HIV-1 protease, the HCV protease (NS3 protein) and the human proteases DPP-4, thrombin, Factor Xa, renin and ACE, which constitute known drug targets with approved inhibitors. The structural similarity between the SARS-CoV-2 protease and some of the selected proteases, in combination with the existence of the same amino acids at certain positions of the substrate cleavage site, such as Ser at the P1' position of the recognition sequence of the HCV protease and thrombin are promising features in the effort to identify effective SARS-CoV-2 protease inhibitors among the approved drugs of the selected proteases. cache = ./cache/cord-264326-teahway7.txt txt = ./txt/cord-264326-teahway7.txt === reduce.pl bib === === reduce.pl bib === id = cord-270498-hh6h50t2 author = Tseng, Chin-Kai title = Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date = 2017-09-19 pages = extension = .txt mime = text/plain words = 4954 sentences = 277 flesch = 47 summary = Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. In this study, our data revealed that celastrol significantly inhibits HCV replication, and that the anti-HCV effect of celastrol was attenuated by the HO-1 specific inhibitor tin mesoporphyrin (SnMP) or HO-1 gene expression silencing. Celastrol-mediated HO-1 induction contributed to the anti-HCV action through inducing antiviral IFN response and inhibiting HCV NS3 protease activity. As shown in Fig. 7B , HO-1 RNA expression levels were induced by celastrol compared with non-celastrol treated cells and the JNK inhibitor SP600125 significantly reduced the HO-1 inductive effect of celastrol. In the present study, we found that a natural product celastrol could effectively inhibit HCV NS3/4A protease activity and enhance IFN-mediated antiviral gene expression through HO-1 induction (Figs. cache = ./cache/cord-270498-hh6h50t2.txt txt = ./txt/cord-270498-hh6h50t2.txt === reduce.pl bib === id = cord-274080-884x48on author = Rumlová, Michaela title = In vitro methods for testing antiviral drugs date = 2018-06-30 pages = extension = .txt mime = text/plain words = 17989 sentences = 941 flesch = 41 summary = For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. cache = ./cache/cord-274080-884x48on.txt txt = ./txt/cord-274080-884x48on.txt === reduce.pl bib === id = cord-260099-mthwab4p author = Li, Yi title = C-type lectin LSECtin interacts with DC-SIGNR and is involved in hepatitis C virus binding date = 2009-02-21 pages = extension = .txt mime = text/plain words = 3479 sentences = 195 flesch = 59 summary = The present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells. About a half of the DC-SIGNR-HEK293T cells were bound to the soluble Fc-LSECtin but not control-Fc protein, whereas only 6% of the mock cells were adhered to LSECtin (Fig. 1c) . Pre-incubation with the soluble LSECtin protein resulted in a dramatic decrease in the affinity of HCV E2 to the HEK293T-LSECtin cells (Fig. 3c) . Our present study suggests that LSECtin, a recently identified C-type lectin, could interact with DC-SIGNR and CD81 and was involved in HCV binding. previously reported that they could not detect the binding of HCV pseudotype particles to LSECtin expressed cells [14] , which is inconsistent with our results. In summary, the present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells. cache = ./cache/cord-260099-mthwab4p.txt txt = ./txt/cord-260099-mthwab4p.txt === reduce.pl bib === id = cord-280330-ibvbowl0 author = Lin, Liang-Tzung title = Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry date = 2013-08-07 pages = extension = .txt mime = text/plain words = 7359 sentences = 351 flesch = 45 summary = While vaccine efforts have proven successful for preventing and eradicating some viral infections, many viruses cannot be targeted by immunization, including dengue virus (DENV), human cytomegalovirus (HCMV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV) [1] [2] [3] [4] [5] . We demonstrated that the two structurally-related compounds mediated their antiviral activities by targeting HSV-1 viral glycoproteins that interact with cell surface GAGs. Taking note of the fact that many viruses employ GAGs to initially bind to the host cell, and based on evidence that CHLA and PUG may act as GAG-competitors, we explored the antiviralpotential of these two tannins against a number of viruses known to interact with GAGs. Viral models included DENV, HCMV, HCV, MV, and RSV ( Table 1 ). We suggest that CHLA and PUG have potential as novel cost-effective and broad-spectrum antivirals for controlling emerging/recurring infections by viruses that engage host cell surface GAGs. Dulbecco's modified Eagle's medium (DMEM) and alpha minimal essential medium (AMEM) were purchased from GIBCO-Invitrogen (Carlsbad, CA, USA). cache = ./cache/cord-280330-ibvbowl0.txt txt = ./txt/cord-280330-ibvbowl0.txt === reduce.pl bib === id = cord-027860-s97hdhh6 author = Zeimet, Anthony title = Infectious Diseases date = 2020-06-22 pages = extension = .txt mime = text/plain words = 28925 sentences = 1728 flesch = 45 summary = Although common upper respiratory bacterial pathogens, such as Moraxella (Branhamella) catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, may be isolated from patients with acute bronchitis, their relevance is questionable because these bacteria can be present in the respiratory tract of healthy individuals. In the treatment of Bordetella pertussis, early administration of a macrolide antibiotic and patient isolation will likely decrease coughing paroxysms and limit spread of disease (Braman, 2006) (SOR: A). Risk factors for Pseudomonas infection include severe structural lung disease (e.g., bronchiectasis) and recent antibiotic therapy, health care-associated exposures or stay in hospital (especially in the ICU). Patients who present with severe infection or whose infection is progressing despite empiric antibiotic therapy should be treated more aggressively; the treatment strategy should be based on results of appropriate Gram stain, culture, and drug susceptibility analysis. For suspected MRSA skin infections, oral treatment options include trimethoprim-sulfamethoxazole, clindamycin, and doxycycline of purulent material when performing incision and drainage in the event that the patient fails to improve and antibiotic coverage becomes necessary. cache = ./cache/cord-027860-s97hdhh6.txt txt = ./txt/cord-027860-s97hdhh6.txt === reduce.pl bib === id = cord-259916-gr6v098c author = Wang, Hongliang title = Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication date = 2016-05-20 pages = extension = .txt mime = text/plain words = 6186 sentences = 252 flesch = 33 summary = Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication. A later study of cells containing a subgenomic HCV replicon reported that the membrane alterations induced by HCV replication consisted in part of double-membrane vesicles (DMVs; Figure 1 ) with a diameter around 200 nm that were also positive on immunoelectron microscopy with antibodies against NS5A and double-stranded RNA (dsRNA) [15] . [10] first showed that expression of viral nonstructural proteins resulted in membrane alterations that morphologically resemble those observed in replicon cells, demonstrating that viral RNA replication is not required for membranous web formation. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex cache = ./cache/cord-259916-gr6v098c.txt txt = ./txt/cord-259916-gr6v098c.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-273555-i1d4quos author = Stättermayer, A. F. title = Letter: does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks? Authors' reply date = 2014-02-04 pages = extension = .txt mime = text/plain words = 1159 sentences = 64 flesch = 47 summary = Authors' reply SIRS, We thank Dr Galmozzi and Dr Lampertico for their comment on our recently published paper on the effect of the dinucleotide frameshift variant in ss469415590 in the interferon (IFN)-k4 gene on interferon/ribavirin treatment and its relationship with the two commonly used single nucleotide polymorphisms (SNP) in IL28B (rs12979860, rs8099917). 1, 2 We agree that our study does not provide insights on the causal relationship between IFNL4 and treatment response in patients with chronic hepatitis C virus (HCV) infection. We would like to remind them that up-regulation of intrahepatic interferon-stimulated genes (ISG) is associated with treatment failure in patients with chronic HCV, and levels of ISG are differently distributed according to different IL28B genotypes. 1 reported a randomised controlled trial comparing oral (100 mg twice daily ferrous sulphate for 3 months) or intravenous (1000 mg ferric carboxymaltose, single-dose infusion) iron supplementation and placebo for anaemia after nonvariceal upper gastrointestinal (GI) bleeding. cache = ./cache/cord-273555-i1d4quos.txt txt = ./txt/cord-273555-i1d4quos.txt === reduce.pl bib === id = cord-284978-vh1x6pg9 author = Jang, Hongje title = Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide date = 2013-02-18 pages = extension = .txt mime = text/plain words = 2968 sentences = 160 flesch = 53 summary = Herein, we developed a multiplexed helicase assay based on graphene oxide (GO) for high-throughput screening of inhibitors of HCV NS3 helicase and severe acute respiratory syndrome coronavirus (SARS CoV) helicase. [10] Herein, we show that the GOHA can be used for measuring the activities of HCV NS3 helicase and SARS CoV helicase in a single mixed solution using two distinct DNA substrates tethered to different fluorophores, and furthermore, for multiplexed high-throughput screening to discover highly selective small-molecule inhibitors of these helicases ( Figure 1 ). A 96-well plate mGOHA was used to screen a 10 000 compound library to discover inhibitors of SARS CoV helicase and HCV NS3 helicase (Figure 3) . [17] Two compounds, antiHCV-Hel-2 and -3, showed a dose-dependent decrease in the Luc/MTT values with the respective half-maximal effective concentrations (EC 50 ) of 188.1 AE 32.6 and 56.8 AE 7.4 mm, indicating that they dose-dependently blocked HCV RNA replication in the cultured Huh-7 cells (Figure 5 b,c) . cache = ./cache/cord-284978-vh1x6pg9.txt txt = ./txt/cord-284978-vh1x6pg9.txt === reduce.pl bib === id = cord-022380-49oti4zg author = Panlilio, Adelisa L title = Occupational Infectious Diseases date = 2009-05-15 pages = extension = .txt mime = text/plain words = 15592 sentences = 809 flesch = 41 summary = Because infectious diseases may represent the most common cause of time lost from work, it is important for the clinician concerned with occupational medicine to understand the relationship of specific infections to specific work environments and practices, and to give at least as much attention to prevention as to diagnosis and treatment. Susceptible household contacts of infected adults and children pose a transmission risk in the workplace during the period of virus shedding, beginning about 10 days before the development of rash (about 1 week after exposure) until 7 days after rash appears. Varicella vaccination is also recommended for susceptible adolescents and adults who will have close contact with persons at high risk for serious complications of acquired varicella, including healthcare personnel and susceptible family contacts of immunocompromised individuals. The ACIP recommends that all healthcare personnel be immune to varicella, either from a reliable history of prior varicella infection or vaccination, to reduce the risk of infection and its complications, and to decrease the possibility of transmission of varicella zoster virus to patients (Table 22. cache = ./cache/cord-022380-49oti4zg.txt txt = ./txt/cord-022380-49oti4zg.txt === reduce.pl bib === id = cord-267867-q52nvn0n author = Chevalier, Christophe title = Inhibition of Hepatitis C Virus Infection in Cell Culture by Small Interfering RNAs date = 2016-12-14 pages = extension = .txt mime = text/plain words = 8001 sentences = 395 flesch = 48 summary = Several siRNAs dramatically reduced or even abrogated the replication of selectable subgenomic HCV replicons upon cotransfection of human hepatoma cells with viral target and siRNAs, or upon transfection of cells supporting autonomous replication of HCV replicon with siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting virus production in cell culture. Several siRNAs dramatically reduced or even abrogated the replication of selectable subgenomic HCV replicons upon cotransfection of human hepatoma cells with viral target and siRNAs, or upon transfection of cells supporting autonomous replication of HCV replicon with siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting virus production in cell culture. We sought to determine whether the siRNAs si240-1a, si244, and si313, shown to be the most efficient in inhibiting the replication of HCV subgenomic replicons both transiently and under selective pressure, are also capable of efficiently blocking virus infection in cell culture. cache = ./cache/cord-267867-q52nvn0n.txt txt = ./txt/cord-267867-q52nvn0n.txt === reduce.pl bib === id = cord-268467-btfz6ye8 author = Schreiber, Steven S. title = Sequence analysis of the nucleocapsid protein gene of human coronavirus 229E date = 1989-03-31 pages = extension = .txt mime = text/plain words = 5035 sentences = 343 flesch = 59 summary = The 3′-noncoding region of the genome contains an 11-nucleotide sequence, which is relatively conserved throughout the Coronavirus family and lends support to the theory that this region is important for the replication of negative-strand RNA. This result suggested that the HCV229E subgenomic mRNAs possess a nested-set structure similar to other coronaviruses and that A34 represented a cDNA clone of either the 3'-end of the genomic RNA or the leader sequence. The 3'-noncoding region contains the sequence TGGAAGAGCCA, 75 nucleotides from the 3'-end (Fig. 4) which is relatively conserved among coronaviruses and is found at approximately the same location in all of these viral genomes (Kapke and Brian, 1986; Skinner and Siddell, 1984; Armstrong et a/., 1983; Lapps et al., 1987; Kamahora et a/., 1988; Boursnell et al., 1985) ( Table 1) . Three intergenic regions of coronavirus mouse hepatitis virus strain A59 genome RNA contain a common nucleotide sequence that is homologous to the 3'end of the viral mRNA leader sequence cache = ./cache/cord-268467-btfz6ye8.txt txt = ./txt/cord-268467-btfz6ye8.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-279202-iyteg4h9 author = Shesheer Kumar, Munpally title = Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients date = 2008-01-05 pages = extension = .txt mime = text/plain words = 2088 sentences = 119 flesch = 53 summary = title: Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients Apart from the core (21 kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the −2/+1 reading frame. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Functional properties of a 16 kDa protein translated from an alternative open reading frame of the core encoding genomic region of hepatitis C virus cache = ./cache/cord-279202-iyteg4h9.txt txt = ./txt/cord-279202-iyteg4h9.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-284693-mgpxnnk0 author = Jothimani, Dinesh title = Post Liver transplant recurrent and de novo viral infections date = 2020-09-26 pages = extension = .txt mime = text/plain words = 6339 sentences = 366 flesch = 41 summary = Advanced recipient age, diabetes mellitus, severe liver disease (Child Pugh >10), IL-28B polymorphism, high HCV RNA >10 7 IU/ml, ischemic/reperfusion injury, CMV, donor age >65 years, cold ischaemic time over 8 hours and warm ischemia over 90 minutes, marginal graft, DCD donor, higher immunosuppression in particular high dose corticosteroids for acute cellular rejection, use of anti-thymocyte globulin were significantly associated with rHCV in the liver allograft 15, 16 . Initial studies with sofosbuvir and ribavirin combination therapy for post-transplant rHCV showed poor drug tolerance, however, the main adverse event was anaemia related to ribavirin in 62% of patients, and subsequent hepatic decompensation related to the low haemoglobin 38 . A study by Pellicelli et al., showed significant adverse events including hepatic decompensation and 25% mortality in those with advanced disease following treatment with daclatasvir and sofosbuvir for post-transplant rHCV 51 . cache = ./cache/cord-284693-mgpxnnk0.txt txt = ./txt/cord-284693-mgpxnnk0.txt === reduce.pl bib === id = cord-265005-e6rpryrh author = Tomasello, Elena title = Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date = 2014-10-30 pages = extension = .txt mime = text/plain words = 18082 sentences = 948 flesch = 40 summary = We will discuss the expression patterns and functions of endosomal TLRs with regards to IFN production in uninfected specialized immune cell types, pDCs and XCR1 + DCs. Plasmacytoid DCs uniquely produce very large amounts of IFNs in response to in vitro stimulation with many viruses, without being infected (46) . Under these conditions, to promote health over disease, the benefits for the host of producing high circulating levels of IFNs in order to induce widespread cell-intrinsic anti-viral defenses might prevail over the deleterious effects that this could cause on certain cell types or tissues. Subcapsular sinus macrophages rapidly become infected by viruses incoming from the lymph and produce large amounts of IFNs. This altruistic suicide prevents virus dissemination to other adjacent cell types and promotes the induction of innate and adaptive anti-viral immunity (87) . cache = ./cache/cord-265005-e6rpryrh.txt txt = ./txt/cord-265005-e6rpryrh.txt === reduce.pl bib === id = cord-280878-1kt51viz author = To, Janet title = Targeting the Channel Activity of Viroporins date = 2016-01-07 pages = extension = .txt mime = text/plain words = 15297 sentences = 701 flesch = 47 summary = For other viroporins, these studies are still mostly in their infancy, although a highresolution structure of the hepatitis C virus (HCV) p7 protein has been recently described (Ouyang et al., 2013) that may be useful for the rational design of p7 channel inhibitors in the future. Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels NMR structure and ion channel activity of the p7 protein from hepatitis C virus Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus cache = ./cache/cord-280878-1kt51viz.txt txt = ./txt/cord-280878-1kt51viz.txt === reduce.pl bib === id = cord-285868-fz5utxss author = Jheng, Jia-Rong title = ER stress, autophagy, and RNA viruses date = 2014-08-05 pages = extension = .txt mime = text/plain words = 9345 sentences = 480 flesch = 38 summary = In addition to regulation of cell death, it is reported that HCV induces the expression of CHOP at mRNA and protein levels and is correlated with autophagy induction; knockdown of CHOP not only increases HCV PAMP-mediated innate immune activation, but also elevates its inhibitory effect on virus replication (Ke and Chen, 2011) . Overexpression of HCV E1 and/or E2 induces the expression of CHOP in a PERK-dependent manner (Chan and Egan, 2005) ; while upon HCV infection, CHOP protein is upregulated by PERK, activating transcription factor (ATF6), and inositol-requiring transmembrane kinase/endonuclease 1 (IRE1) collectively. It was reported that rotavirus NSP4 viroporin initiates autophagy to transport viral proteins to sites of virus replication for assembly of mature particles, which involves an increase of cytoplasmic calcium and subsequent activation of the CaMKK-β-AMPK pathway. Regulated IRE1-dependent decay pathway is activated during Japanese encephalitis virus-induced unfolded protein response and benefits viral replication cache = ./cache/cord-285868-fz5utxss.txt txt = ./txt/cord-285868-fz5utxss.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-286719-1xjmlwqr author = Draz, Mohamed Shehata title = Applications of gold nanoparticles in virus detection date = 2018-02-15 pages = extension = .txt mime = text/plain words = 18990 sentences = 901 flesch = 37 summary = The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. These techniques represent the majority of molecular techniques applied in virus detection and include various types of target amplification techniques (e.g., PCR, loop-mediated isothermal amplification (LAMP), transcription-mediated amplification, and nucleic acid sequence-based amplification), signal amplification techniques (e.g., branched DNA and hybrid capture), and probe amplification techniques (e.g., ligase chain reaction and strand-displacement amplification). [70] developed an impedimetric electrochemical assay for the detection of AIV M gene sequences based on measuring changes in the impedimetric behavior of the electrode when the target DNA hybridizes with the capture DNA probes immobilized onto its surface and is subsequently labeled by AuNPs via streptavidin/ biotin interaction (Fig. 12C) . cache = ./cache/cord-286719-1xjmlwqr.txt txt = ./txt/cord-286719-1xjmlwqr.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-291321-ao80xk11 author = Khan, Mohsin title = Mitochondrial dynamics and viral infections: A close nexus date = 2015-10-31 pages = extension = .txt mime = text/plain words = 9764 sentences = 538 flesch = 26 summary = Hepatitis C virus [8, 9] Enhanced fission and mitophagy Core, E1-E2 Activation of Drp-1, and mitochondrial translocation of Parkin Inhibition of apoptosis and innate immune response, facilitates persistent infection Pseudorabies virus [136] Fragmented mitochondria Glycoprotein B (GB) Altered functioning of Miro protein Affects intracellular calcium signaling and mitochondrial motility Human cytomegalovirus [130] Enhanced fission vMIA Affects mechanism of Bax Inhibition of apoptosis Epstein-Barr virus [128] Enhanced fission LMP2A Up regulation of Drp-1 Cell migration and apoptosis Hepatitis B virus [7] Enhanced fission and mitophagy HBx Parkin and PINK1 up-regulation and Drp-1 phosphorylation Inhibition of apoptosis and innate immune response, facilitates persistent infection Influenza A virus [98] Induction of mitophagy Unknown The NOD2 and RIPK2 promote ULK1 phosphorylation to induce mitophagy Inhibits inflammasome activation and reduces disease severity Influenza A virus [137, 138] Induction of mitochondrial fragmentation inhibition of mitochondrial β-oxidation of fatty acids [109] . cache = ./cache/cord-291321-ao80xk11.txt txt = ./txt/cord-291321-ao80xk11.txt === reduce.pl bib === === reduce.pl bib === id = cord-294842-aesiff1f author = Romero-Brey, Inés title = Membranous Replication Factories Induced by Plus-Strand RNA Viruses date = 2014-07-22 pages = extension = .txt mime = text/plain words = 11038 sentences = 520 flesch = 40 summary = Three-dimensional reconstructions of the WNV KUN replication sites revealed an intimate association of the rough ER (rER) with the bounding membrane of the VPs [20] (Figure 2B ), resembling the vesicles observed in DENV-infected cells. In cells infected with TBEV, one of the most important tick-transmitted viruses in Europe and Asia, virus particles and membrane-connected vesicles were also observed inside the ER [25] , similar to what was described for DENV and WNV KUN . Importantly, pulse-radiolabeling experiments localized sites of active RNA replication to the outer surface of single-membrane tubules [71] and isolation of the membranous replication factories and their subsequent visualization by EM revealed that they form rosette-like structures composed of virus-induced cytoplasmic vesicles [124] . Formation of plant RNA virus replication complexes on membranes: Role of an endoplasmic reticulum-targeted viral protein cache = ./cache/cord-294842-aesiff1f.txt txt = ./txt/cord-294842-aesiff1f.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-293790-7hyelm88 author = Guévin, Carl title = Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection date = 2010-09-01 pages = extension = .txt mime = text/plain words = 5267 sentences = 290 flesch = 54 summary = title: Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection To identify novel cellular factors that may play an essential role in HCV RNA replication, we have previously screened a human liver cDNA library for proteins interacting with the HCV NS5B RNAdependent RNA polymerase (RdRp). Here we report that ATG5, a protein required for the formation of DMV in embryonic stem cell (Mizushima et al., 2001) , specifically interacts with HCV NS5B. As a control, a panel of proteins (RAR-β, RAR-α, HCV core, and nonstructural protein: NS3 prot , NS3 hel , NS4A, and NS4B) cloned in the GAL4 DNA binding domain was tested for interaction with ATG5. A. Soluble yeast extracts containing NS5BΔ21 (N-terminal c-myc tag) and ATG5 (N-terminal HA tag) were incubated with different monoclonal antibodies and the immunoprecipitates were pulled down using protein A/G beads. cache = ./cache/cord-293790-7hyelm88.txt txt = ./txt/cord-293790-7hyelm88.txt === reduce.pl bib === id = cord-293653-u2qrxq6t author = Watashi, Koichi title = Cyclophilin and Viruses: Cyclophilin as a Cofactor for Viral Infection and Possible Anti-Viral Target date = 2007-02-05 pages = extension = .txt mime = text/plain words = 4891 sentences = 304 flesch = 46 summary = In addition to these cellular events, a number of reports demonstrated that CyP plays a critical role in the life cycle of viruses, especially human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The action of PPIases leads to changes in protein conformation (Takahashi, 1999) , but the binding of CsA and FK506 to CyP and FKBP, respectively, inhibits the activity of these enzymes (Fischer et al. The CsA/CyP or FK506/FKBP complex, subsequently interacts with and inhibits calcineurin (CN), a phosphatase involved in the activation of the transcription factor NF-AT. Members of the CyP family play roles in a variety of cellular processes including the immune response, transcription, mitochondrial function, cell death, and chemotaxis, as described below. However, the best-characterized role identified for CyPA is not in normal cellular physiology, but rather as co-factor during the human immunodefi ciency virus-1 (HIV-1) viral life cycle (See below). cache = ./cache/cord-293653-u2qrxq6t.txt txt = ./txt/cord-293653-u2qrxq6t.txt === reduce.pl bib === id = cord-298033-kzdp9edn author = Domingo, Esteban title = Quasispecies dynamics in disease prevention and control date = 2019-11-08 pages = extension = .txt mime = text/plain words = 16346 sentences = 735 flesch = 37 summary = Quasispecies dynamics in disease prevention and control following statement will be obvious to the reader: "If a single mutation is able to confer resistance to an antiviral agent, and the mutation does not cause a significant selective disadvantage to the virus (fitness decrease) in the considered environment, a drug-resistant virus mutant will be present in most, if not all, virus populations" (Domingo, 1989) . The phenotypic barrier to drug resistance is equivalent to the fitness cost inflicted upon the virus by the mutations and corresponding amino acid substitution(s) required for resistance [Fitness cost is treated in Chapter 4 (Section 4.6) and in Chapter 7 (Section 7.4.2) in connection with the frequency of monoclonal antibody-or cytotoxic T-cell-escape mutants in viral populations]. For viruses that replicate in cell culture, it is possible to estimate the minimal viral population size needed to select a drug-resistant mutant which is generally positively correlated with the genetic barrier ( Fig. 8.5 ). cache = ./cache/cord-298033-kzdp9edn.txt txt = ./txt/cord-298033-kzdp9edn.txt === reduce.pl bib === id = cord-293646-d4qcckh1 author = Meanwell, Nicholas A. title = Chapter 22. Non-HIV antiviral agents date = 2003-12-31 pages = extension = .txt mime = text/plain words = 4178 sentences = 198 flesch = 46 summary = The first small molecule inhibitor of Hepatitis C Virus (HCV), the NS3 protease inhibitor BILN-2061, entered phase 2 clinical trials, producing a striking reduction in viral load in treated individuals. Inhibitors of Hepatitis B Virus (HBV) -Adefovir dipivoxil iHepsera'") (1) was approved in the US for the treatment of HBV on September 20', 2002 and in the European Union on March 1 lth, 2003, providing a second small molecule antiviral to add to lamivudine (3TC) and the injectable protein IFNa as the only approved agents for treating HBV infection. Pyridinedicarboxamide S represents the first report of a non-nucleoside inhibitor of HBV reverse transcriptase enantiomer of q is active in cell culture and appears to prevent proper formation of the viral nucleocapsrd. A significant advance towards establishing a correlation between replicon inhibition and clinical efficacy was recently accomplished with the disclosure of preliminary clinical data for BILN-2061, a selective inhibitor of the NS3 serine protease of HCV that is structurally related to 13. cache = ./cache/cord-293646-d4qcckh1.txt txt = ./txt/cord-293646-d4qcckh1.txt === reduce.pl bib === id = cord-302295-nblmshni author = Savva, Athina title = Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases date = 2013-11-18 pages = extension = .txt mime = text/plain words = 10282 sentences = 533 flesch = 39 summary = TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Recombinant human activated protein C (rhAPC, Xigris®, Eli Lilly), the only drug specifically registered for sepsis, has recently been withdrawn from the market following the negative results from the PROWESS-SHOCK study that did not show reduction in mortality at 28 or 90 days in patients with septic shock (4) . The discovery of TLRs and their involvement in innate immune responses has attracted much interest into the development of drugs for controlling infections and improving sepsis management. Moreover, upon infection, innate immune cells will likely sense several MAMPs via several TLRs and non-TLR PRRs. For example, Gram-negative bacteria express MAMPs that may trigger redundant inflammatory pathways through TLR2 (lipopeptides), TLR4 (LPS), TLR5 (flagellin), TLR7 (ssRNA), and TLR9 (bacterial DNA). cache = ./cache/cord-302295-nblmshni.txt txt = ./txt/cord-302295-nblmshni.txt === reduce.pl bib === id = cord-299719-bvdsz626 author = Fournier, C. title = Are trans‐complementation systems suitable for hepatitis C virus life cycle studies? date = 2013-02-14 pages = extension = .txt mime = text/plain words = 4511 sentences = 262 flesch = 47 summary = Next, the development of cell-culture-grown hepatitis C virus (HCVcc) systems that can assemble and release of infectious viral particles has made it possible to the study structural regions using trans-complementation systems. A series of replicon RNAs carrying mutations (in the NS3, NS4B, NS5A and NS5B regions) that abolished replication were transfected into Huh-7 hepatoma cells harbouring autonomous replicating HCV helper RNAs. In this context, only NS5A mutations in the low complexity sequence I (LCS I) domain have been efficiently rescued ( Table 1 ). These results have clarified the role of Core, p7 and LDs in pseudo-infectious particle production and have indicated that some steps of virus assembly take place around LDs. Various trans-packaging systems have been developed with subgenomic replicons. Trans-encapsidation of hepatitis C virus subgenomic replicon RNA with viral structure proteins Naturally occurring hepatitis C virus subgenomic deletion mutants replicate efficiently in Huh-7 cells and are trans-packaged in vitro to generate infectious defective particles cache = ./cache/cord-299719-bvdsz626.txt txt = ./txt/cord-299719-bvdsz626.txt === reduce.pl bib === id = cord-303189-ktl4jw8v author = Coccia, Eliana M. title = Early IFN type I response: Learning from microbial evasion strategies date = 2015-03-31 pages = extension = .txt mime = text/plain words = 15202 sentences = 738 flesch = 40 summary = Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. In these cells, the HCV-induced miR-21 has been recently reported to be involved in evasion of IFN-I production and stimulation of HCV replication, upon suppression of MyD88 and IRAK1 expression, that is required for the TLR7-mediated sensing of the virus [100] . Amongst RNA viruses that, as HCV, can establish a persistent infection, HIV-1, a lentivirus from the Retroviridae family, represents a paradigm for its ability to prevent or circumvent the innate immune response mediated by IFN-I. Overall, viruses as HCV and HIV-1 have evolved nifty strategies to dampen the host innate response in cells where a productive infection may take place, while they induce infection-independent mechanisms in non-permissive cells to facilitate the viral life cycle and promote a chronic inflammation. cache = ./cache/cord-303189-ktl4jw8v.txt txt = ./txt/cord-303189-ktl4jw8v.txt === reduce.pl bib === id = cord-284376-plwyjhl8 author = Fu, Xinmiao title = Simulating and forecasting the cumulative confirmed cases of SARS-CoV-2 in China by Boltzmann function-based regression analyses date = 2020-05-31 pages = extension = .txt mime = text/plain words = 14726 sentences = 782 flesch = 49 summary = All specimens tested negative by direct examination for PJ, whereas 27 were positive by real-time PCR (BAL, n = 18; sputa, n = 7, and TA, n = 2); Following stringent clinical, microbiological and imaging criteria ( Table 1 ) , PJP was deemed to be the most probable diagnosis in 12 episodes occurring in unique patients. In contrast, corticosteroid use within the month before sampling was not different between The probability of Pneumocystis jirovecii (PJ) pneumonia (PJP) for each patient was retrospectively evaluated by an expert committee including infectious diseases and microbiology specialists at both centers, on the basis of (i) documented PJ presence in respiratory specimens by microscopy; (ii) compatibility of clinical signs and symptoms (at least 2 of the following: subtle onset of progressive dyspnea, pyrexia, nonproductive cough, hypoxaemia and chest pain), (iii) compatible (suggestive) radiological findings (chest radiograph and/or high-resolution computed tomographic scan detection of interstitial opacities and/or diffuse infiltration infiltrates); (iv) complete resolution of symptoms after a full course of anti-PJP treatment; (v) absence of alternative diagnosis. cache = ./cache/cord-284376-plwyjhl8.txt txt = ./txt/cord-284376-plwyjhl8.txt === reduce.pl bib === id = cord-293857-o8rlqsq5 author = Ghosh, Arun K. title = Organic Carbamates in Drug Design and Medicinal Chemistry date = 2015-01-07 pages = extension = .txt mime = text/plain words = 18165 sentences = 1121 flesch = 41 summary = Also, we will outline successful designs of organic carbamates, including a variety of cyclic ether-derived carbamates, as suitable amide bond surrogates leading to a wide range of novel organic carbamates as potent HIV-1 protease, βsecretase, serine protease, and cysteine protease inhibitors. 172−174 A number of FDA-approved HIV protease inhibitor drugs contain an important carbamate functionality. 179, 230 Further development of carbamate-derived novel HIV-1 protease inhibitors is shown in Figure 12 . This backbone binding strategy to combat drug resistance led to the development of a series of very potent carbamate-derived protease inhibitors. Carbamate derivative 281 (Figure 24 ), a diphenyl phosphonate ester containing a Cbz group and bearing a single amino acid side chain, showed very good inhibitory activity against human plasma kallikrein, useful for the treatment of hereditary angioedema. Design and synthesis of potent HIV-1 protease inhibitors incorporating hexahydrofuropyranol-derived high affinity P(2) ligands: structure-activity studies and biological evaluation cache = ./cache/cord-293857-o8rlqsq5.txt txt = ./txt/cord-293857-o8rlqsq5.txt === reduce.pl bib === id = cord-298736-9bvyp21d author = Gerold, Gisa title = Decoding protein networks during virus entry by quantitative proteomics date = 2016-06-15 pages = extension = .txt mime = text/plain words = 12159 sentences = 626 flesch = 38 summary = In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) . While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM). Of note, high resolution proteomics can not only reveal transient interactions of VAP with enzymes, but also has the potential to identify proteolytic cleavage sites and redox modifications in VAPs. It is conceivable that virus induced protein interactions during entry not only serve to promote the virus uptake pathway, but can also help cloak viruses and lead to immune evasion. cache = ./cache/cord-298736-9bvyp21d.txt txt = ./txt/cord-298736-9bvyp21d.txt === reduce.pl bib === id = cord-305303-82n96ukr author = Shapira, Assaf title = Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date = 2012-02-16 pages = extension = .txt mime = text/plain words = 10132 sentences = 431 flesch = 42 summary = As shown in Figure 2 , similar numbers of surviving colonies were observed when the cells were transfected with the plasmids encoding mCherry-NS3 activated MazF or the red fluorescent protein alone, suggesting that expression of NS3-activable ribonuclease in naïve HEK293 T-REx cells (that do not express NS3) cause minimal toxicity, if any. The ER membrane-targeted zymoxin colocalizes with NS3 protease in vivo Previously we described a HEK293 cell line which inducibly expresses (by addition of tetracycline) a fusion between EGFP and the coding sequence of the full length NS3 (including the helicase domain) followed by NS4A from HCV 1a genotype [10] . When infection reached ,50% (about 50% of the cultured cells showed expression of the HCV-core protein, as detected by immuno-staining and fluorescence microscopy), the mixed culture and a culture of uninfected cells were treated with NS3 activated MazF or uncleavable-MazF encoding adenoviruses at MOI of ,3. cache = ./cache/cord-305303-82n96ukr.txt txt = ./txt/cord-305303-82n96ukr.txt === reduce.pl bib === id = cord-307556-k2lavvca author = Jang, Hongje title = Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide date = 2013-02-18 pages = extension = .txt mime = text/plain words = 2983 sentences = 154 flesch = 53 summary = Herein, we developed a multiplexed helicase assay based on graphene oxide (GO) for high-throughput screening of inhibitors of HCV NS3 helicase and severe acute respiratory syndrome coronavirus (SARS CoV) helicase. [10] Herein, we show that the GOHA can be used for measuring the activities of HCV NS3 helicase and SARS CoV helicase in a single mixed solution using two distinct DNA substrates tethered to different fluorophores, and furthermore, for multiplexed high-throughput screening to discover highly selective small-molecule inhibitors of these helicases ( Figure 1 ). A 96-well plate mGOHA was used to screen a 10 000 compound library to discover inhibitors of SARS CoV helicase and HCV NS3 helicase (Figure 3) . [17] Two compounds, antiHCV-Hel-2 and -3, showed a dose-dependent decrease in the Luc/MTT values with the respective half-maximal effective concentrations (EC 50 ) of 188.1 AE 32.6 and 56.8 AE 7.4 mm, indicating that they dose-dependently blocked HCV RNA replication in the cultured Huh-7 cells (Figure 5 b,c) . cache = ./cache/cord-307556-k2lavvca.txt txt = ./txt/cord-307556-k2lavvca.txt === reduce.pl bib === id = cord-286334-d9v5xtx7 author = Li, Rui title = Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV date = 2020-04-30 pages = extension = .txt mime = text/plain words = 12955 sentences = 719 flesch = 50 summary = More detailed monitoring on how these physiological parameters change over time (perhaps including more complex cytokine studies), in these severely ill, influenza A(H1N1)pdm09-infected patients admitted to ICU-ECMO units, may eventually yield data to improve their management and clinical outcomes. 5 In the current study, we characterized a new HCV subtypes among chronic hepatitis C patients in Yunnan, China, initially designated as 6xi, further analyzed its evolutionary history and investigated its baseline RAS by next generation sequencing (NGS) method. The samples met the following inclusion criteria: (1) hepatitis C antibody-positive for 6 months with normal serum alanine aminotransferase (ALT) levels; (2) subject was residing in Yunnan province and was over 18 years old; (3) complete demographic information and clinical data were available; (4) consented to the use of patient information in studies on HCV epidemics; and (5) were treatment-naïve during sampling. cache = ./cache/cord-286334-d9v5xtx7.txt txt = ./txt/cord-286334-d9v5xtx7.txt === reduce.pl bib === id = cord-305039-grsv06j7 author = Flego, Michela title = Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases date = 2013-01-04 pages = extension = .txt mime = text/plain words = 10985 sentences = 476 flesch = 37 summary = As for HIV, mAbs directed against spike viral proteins, as well as against host receptors, may act at an early stage of infection by preventing the binding of the virus on the cell surface. In some chronic viral infections, virus-specific immune cells may persist in a 'non-functional' state, because of an imbalance of immunoregulatory signals involving multiple inhibitory and activating receptors, triggered by soluble factors and/or cell surface ligands. Therapeutic approaches using specific mAbs to block host immunosuppressive molecules (antagonism) or to trigger activating receptors (agonism) may be a valid strategy to restore immune cell function and treat various chronic viral infections. In a proof-of-concept passive immunization trial with humans, it has been demonstrated that a cocktail of the three broadly neutralizing mAbs -2G12, 4E10 and 2F5was able to delay viral rebound in patients whose infections were fully suppressed by antiretroviral treatment before administration of the antibodies [76] . cache = ./cache/cord-305039-grsv06j7.txt txt = ./txt/cord-305039-grsv06j7.txt === reduce.pl bib === id = cord-305263-fgwf6wy3 author = Wang, Ben X. title = The yin and yang of viruses and interferons date = 2012-02-07 pages = extension = .txt mime = text/plain words = 6285 sentences = 294 flesch = 38 summary = IFN therapy therefore has the advantage over DAA treatments in that, in addition to stimulating genes that block viral replication in infected cells, IFNs activate other innate and adaptive immune responses to combat the virus. For example, polymorphisms in host genes encoding proteins associated with regulation of an IFN response such as interferon receptor a-chain (IFNAR1) [10] , the IFN-inducible myxovirus resistance GTPase protein, Mx [11] , the IFN-inducible 2 0 ,5 0 -oligoadenylate synthetase (OAS) [12] and the suppressor of cytokine signaling (SOCS) 3 associated with regulation of an IFN response [13] , are predictive markers linked with the rate of sustained virological response (SVR) to HCV infection following IFN-a treatment. Remarkably, distinct highly pathogenic respiratory viruses, namely influenza viruses and the SARS-CoV, encode nonstructural proteins in their genomes that function as virulence factors that specifically target the host innate IFN response, further emphasizing the importance of IFNs as broad-spectrum antivirals. cache = ./cache/cord-305263-fgwf6wy3.txt txt = ./txt/cord-305263-fgwf6wy3.txt === reduce.pl bib === id = cord-300154-3p7tjp5j author = Pezacki, John Paul title = Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy date = 2011-02-14 pages = extension = .txt mime = text/plain words = 7750 sentences = 370 flesch = 39 summary = Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. cache = ./cache/cord-300154-3p7tjp5j.txt txt = ./txt/cord-300154-3p7tjp5j.txt === reduce.pl bib === id = cord-307817-2vy28i4m author = Lou, Zhiyong title = Current progress in antiviral strategies date = 2014-01-14 pages = extension = .txt mime = text/plain words = 7555 sentences = 343 flesch = 36 summary = The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Based on the complex structure of the PA C-terminal domain (PA C ) and the first 25 amino acids of PB1 [99] , a subset of modifications on N-terminal peptide of PB1 was shown to diminish the binding affinity of PA and PB1, inhibit polymerase activity, and attenuate the replication of influenza virus [100] [101] [102] . Because both the polymerase complex and NP show significant conservation between different influenza viruses, these results demonstrated that targeting the formation of viral RNP is a valid approach to the development of small molecule therapies against serious antiviral resistance to currently available drugs, such as adamantanes or neuraminidase inhibitors. cache = ./cache/cord-307817-2vy28i4m.txt txt = ./txt/cord-307817-2vy28i4m.txt === reduce.pl bib === id = cord-312080-pu6m4qad author = He, Bing title = Three-dimensional cell culture models for investigating human viruses date = 2016-10-27 pages = extension = .txt mime = text/plain words = 9036 sentences = 454 flesch = 38 summary = This review focuses on the recent progress of human virological research with 3D cell culture models, including human viral growth, replication, proliferation, infection, viral life cycle, virus-host interaction and the development of antiviral drugs. A multitude of research has shown that RWV-derived models utilizing human cells are a valuable tool for investigating viral growth, replication, viral infection, viral entry, the viability of virions and virus-host interaction (Margolis et al., 1997; Long et al., 1998; Nickerson et al., 2007; Straub et al., 2007; Barrila et al., 2010; Berto et al., 2013; Goodwin et al., 2015) . As keratinocytes are the main target cells for productive infection in vivo for VZV, characterization of viral replication in organotypic raft cultures of these cells represents a very relevant model for studying virus-host cell interactions and antiviral agents (Andrei et al., 2005) . cache = ./cache/cord-312080-pu6m4qad.txt txt = ./txt/cord-312080-pu6m4qad.txt === reduce.pl bib === id = cord-305393-96mrxt8a author = Lai, Yvonne title = Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date = 2011-10-10 pages = extension = .txt mime = text/plain words = 9604 sentences = 587 flesch = 60 summary = Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. Transfection of two plasmids, one containing an interferon stimulated response element (ISRE) promoter-driven firefly luciferase and a second encoding a constitutively expressed Renilla luciferase allow the analysis of TLR3 activation by different RNAs. HEK 293T cells expressing WT TLR3 responded to poly(I:C) (1-2 mg/ml), better than viral dsRNAs (1-2 mg/ml) purified from Reovirus and BPEV (Fig. 1B) . cache = ./cache/cord-305393-96mrxt8a.txt txt = ./txt/cord-305393-96mrxt8a.txt === reduce.pl bib === id = cord-305085-bv7udg9k author = Lawrence, Robert M. title = Chapter 13 Transmission of Infectious Diseases Through Breast Milk and Breastfeeding date = 2011-12-31 pages = extension = .txt mime = text/plain words = 45849 sentences = 2358 flesch = 45 summary = Postnatal exposure of susceptible infants to CMV, including premature infants without passively acquired maternal antibodies against CMV, infants born to CMV-seronegative mothers, and immunodeficient infants, can cause significant clinical illness (pneumonitis, hepatitis, thrombocytopenia).* In one study of premature infants followed up to 12 months, Vochem et al 430 found CMV transmission in 17 of 29 infants (59%) exposed to CMV virolactia and breastfed compared with no infants infected of 27 exposed to breast milk without CMV. 38, 104, 121 Laboratory reports demonstrate the presence of cell-free virus and cell-associated virus in breast milk as well as various immunologic factors that could block or limit infection.* A dose-response relationship has been observed, correlating the HIV viral load in human milk as well as a mother' s plasma viral load with an increased transmission risk for the breastfed infant. 76 No case of transmission of yellow fever virus from an infected mother to her infant via breastfeeding or breast milk has been reported. cache = ./cache/cord-305085-bv7udg9k.txt txt = ./txt/cord-305085-bv7udg9k.txt === reduce.pl bib === id = cord-306934-29ljbl7g author = Tonelli, Michele title = Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date = 2009-07-01 pages = extension = .txt mime = text/plain words = 8526 sentences = 442 flesch = 58 summary = Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values. First of all, the binding site identified by our procedure is very close to the putative binding site proposed for two allosteric inhibitors of BVDV RdRp, VP32947 and BPIP, 23 Table 5 Cytotoxicity against MT-4, MDBK, BHK and Vero-76 cell lines and YFV, Reo-1, CVB-2, RSV, HSV-1 and Sb-1 inhibitory activity of triazene derivatives of structure F and G Tables 3 and 4. In view of these considerations, molecular modeling investigations were performed to study wether the active compounds of structures A-C could target the BVDV RNA-dependent RNA-polymerase (RdRp), which shares some structural similarity with HCV RdRp. Indeed a good agreement was observed between the trend exhibited by the IC 50 (calculated from the estimated free energies of binding) and the corresponding biological activities determined for these compounds in BVDV infected MDBK cell line. cache = ./cache/cord-306934-29ljbl7g.txt txt = ./txt/cord-306934-29ljbl7g.txt === reduce.pl bib === id = cord-321230-b5a1z14w author = Samji, Hasina title = Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada date = 2020-10-19 pages = extension = .txt mime = text/plain words = 5467 sentences = 225 flesch = 48 summary = Lastly, if an underlying cause of death code was recorded as ICD-10 R99 (other ill-defined and unspecified causes, usually assigned when cause of death is still under investigation), and manner of death was listed as "pending," "accident," or "undetermined," we re-categorized the death as drug-related if the death met the following criteria: attributable to a person aged 20 to 64 years who also injects drugs (defined as any drug-related diagnoses, use of injection drugs, record of opioid agonist therapy dispensation or injection related infection using physician diagnostic and billing data, hospitalizations, prescription data, vital statistics and emergency room data), based on validation studies in the US and in the BC-HTC (Centers for Disease Control and Prevention, 2004; to mitigate the impact of missing data on the analysis. We compared PLHCV and HCV-negative individuals who died of DRDs, estimated annual age and sex-adjusted drug-related mortality rates per 100,000 person-years (PY) for these groups and examined trends over time by sex. cache = ./cache/cord-321230-b5a1z14w.txt txt = ./txt/cord-321230-b5a1z14w.txt === reduce.pl bib === id = cord-311823-85wj08gr author = Katze, Michael G. title = Innate immune modulation by RNA viruses: emerging insights from functional genomics date = 2008 pages = extension = .txt mime = text/plain words = 9154 sentences = 392 flesch = 36 summary = In this section, we review recent studies in which genomic approaches have been used to provide new information on how viruses trigger and regulate innate immune pathways, and to evaluate the use of type I IFN-based therapy as a means to enhance the innate immune response to HCV. In RIg-I-deficient cells, influenza virus fails to elicit the expression of IFNβ and of many ISgs, including key antiviral mediators such as IRF3, STAT1 (signal transducer and activator of transcription 1), IFIT1 (IFN-induced protein with tetratricopeptide repeats 1; also known as ISg56) and ISg54 (also known as IFIT2). Although these studies have provided considerable information regarding the genes activated downstream of TlR activation, it will be advantageous to extend genomic analyses in the context of viral infection using cells lacking the expression of specific TlRs. The ability of a virus to establish an infection depends, at least to some extent, on its ability to block the host innate immune response or to modulate the activity of antiviral effector proteins. cache = ./cache/cord-311823-85wj08gr.txt txt = ./txt/cord-311823-85wj08gr.txt === reduce.pl bib === id = cord-314753-xflhxb13 author = Manso, Carmen F. title = Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date = 2017-06-23 pages = extension = .txt mime = text/plain words = 6333 sentences = 296 flesch = 48 summary = The percentage of reads mapping to RNA virus genomes in the rRNA-depleted BBV Panel samples was between 40 and 150-fold higher than in corresponding untreated controls. The depth plots in Fig. 3 again show unbiased and even coverages across both genomes, and the percentages of reads mapping to viral targets was again much higher in the rRNA-depleted sample than in the untreated comparator (61-fold and 85-fold for HCV and HPgV respectively). By depleting host-derived nucleic acids and making modifications to an existing library preparation protocol to account for ultra-low RNA input quantities, we have been able to reconstruct effectively full-length genomes of HCV, HEV and HIV from plasma samples with viral loads of 10 4 IU/ml (copies/ml for HIV) and substantial fractions of complete genomes at 10 3 IU/ml. Additionally, our system was able to recover viral sequences from a panel of diverse RNA viruses diluted in human plasma, with a broad correlation between the genomic coverage and depth metrics and approximate concentration. cache = ./cache/cord-314753-xflhxb13.txt txt = ./txt/cord-314753-xflhxb13.txt === reduce.pl bib === id = cord-321053-lgae22f8 author = Gerold, Gisa title = Opportunities and Risks of Host-targeting Antiviral Strategies for Hepatitis C date = 2013-10-04 pages = extension = .txt mime = text/plain words = 9393 sentences = 470 flesch = 42 summary = Numerous in vitro studies in combination with a growing number of HCV sequencing data from patients undergoing DAA treatment underline that the virus can develop drug-resistance and fitness restoring compensatory mutations [11] . An emerging third group of antivirals, so called hosttargeting antivirals (HTA), may be part of such future combination therapies, in particular as HTAs hold the promise of overcoming some of the caveats of DAAs. HTAs are antibodies, RNAs or small molecules, which interfere with host factors needed for HCV propagation. On the one hand, this demonstrates that HCV can in theory evade HTA therapy by mutating the viral binding partner of the targeted host factor and in fact suggests a low genetic barrier to resistance. Targeting HCV RNA Replication: Phosphatidylinositol 4-kinase III alpha (PI4KIIIα) Genome wide RNA interference screens and in depth cell culture replication assays with HCV replicons and full length infectious virus have revealed numerous additional host dependency factors, that could in principle serve as antiviral targets [99] [100] [101] [102] [103] [104] [105] [106] [107] . cache = ./cache/cord-321053-lgae22f8.txt txt = ./txt/cord-321053-lgae22f8.txt === reduce.pl bib === id = cord-319754-5isw53wl author = Balgoma, David title = Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update date = 2020-08-31 pages = extension = .txt mime = text/plain words = 12092 sentences = 541 flesch = 41 summary = Some viruses may use different entry mechanisms, this feature being likely dependent upon the membrane lipid composition of the host cell they infect as well as the particular cell surface factor attachment used. The question regarding whether the lipid-raft domains may serve as platforms to concentrate the proteins required for viral entry and, even though some evidence exists, to activate signaling pathways inside the host cell still remains unsolved. More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . cache = ./cache/cord-319754-5isw53wl.txt txt = ./txt/cord-319754-5isw53wl.txt === reduce.pl bib === id = cord-325989-nf6ouaq3 author = Es-Saad, Salwa title = Regulators of innate immunity as novel targets for panviral therapeutics date = 2012-09-24 pages = extension = .txt mime = text/plain words = 3731 sentences = 201 flesch = 34 summary = The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. In the near future, targeting specific regulators of PRR-mediated innate response to withdraw viral subversion mechanisms, and access to novel surrogate measurable effector markers, hold the promise of new panviral therapeutics that will minimize adverse effects associated with type I IFN therapy. cache = ./cache/cord-325989-nf6ouaq3.txt txt = ./txt/cord-325989-nf6ouaq3.txt === reduce.pl bib === === reduce.pl bib === id = cord-324054-d71rj29o author = Zhang, Xuming title = The hemagglutinin/esterase gene of human coronavirus strain OC43: Phylogenetic relationships to bovine and murine coronaviruses and influenza C virus date = 1992-01-31 pages = extension = .txt mime = text/plain words = 2355 sentences = 147 flesch = 64 summary = Abstract The complete nucleotide sequences of the hemagglutinin/esterase (HE) genes of human coronavirus (HCV) strain OC43 and bovine respiratory coronavirus (BRCV) strain G95 were determined from single-stranded cDNA fragments generated by reverse transcription of virus-specific mRNAs and amplified by polymerase chain reaction. Phylogenetic analysis suggests that the HE genes of coronaviruses and influenza C virus have a common ancestral origin, and that bovine coronaviruses and HCV-OC43 are closely related. We report here the complete nucleotide sequence of the HE genes of HCV-OC43 and BRCV-G95, and their phylogenetic relatedness to BCVs, MHV, and ICV. The predicted amino acid sequences of the HE genes from HCV-OC43 and BRCV-G95 (Fig. l) , BCVMost importantly, the putative acetylesterase active site (F-G-D-S) (at amino acids 72 to 75 in Fig. 2) is conserved in all HE proteins of human, bovine, and murine coronaviruses and ICV. cache = ./cache/cord-324054-d71rj29o.txt txt = ./txt/cord-324054-d71rj29o.txt === reduce.pl bib === id = cord-317595-siwzjeea author = Forni, Diego title = Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV date = 2018-05-01 pages = extension = .txt mime = text/plain words = 9944 sentences = 505 flesch = 49 summary = Herein, we apply an evolutionary approach to shed light into HCV origin, to analyze its adaptation to human populations, and to verify if the emergence of drug-resistant variants is a result of positive selection. We used Single-Likelihood Ancestor Counting (SLAC) and fixed effects likelihood (FEL) (Kosakovsky Pond and Frost, 2005) to calculate the rates of nonsynonymous and synonymous changes at each site in the structural and in the non-structural region alignments (analyses were performed on alignments split on the basis of the recombination breakpoint detected by GARD). The observation that the positively selected sites are involved in HCV binding and infectivity suggests that hepaciviruses contributed to shape the genetic diversity of CD81 in bats. Using an evolutionary model that accounts for variation in the pressure of natural selection across sites and branches, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago, with a lower bound estimate of ∼5200 years before present. cache = ./cache/cord-317595-siwzjeea.txt txt = ./txt/cord-317595-siwzjeea.txt === reduce.pl bib === id = cord-318853-mxyxwkhx author = Sallie, Richard title = Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases date = 2005-08-22 pages = extension = .txt mime = text/plain words = 10541 sentences = 396 flesch = 25 summary = Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. Hence, as relative concentrations of wild-type and variant viral proteins vary, alteration of both processivity and fidelity of RNA pol results, permitting viruses to adaptively respond to environmental changes, including immune recognition and reaction to evolving cell receptors. As clear evidence exists for viral disruption of leptin function [106] and virus-associated weight gain in humans [107] and monkeys [108] , is it possible the global epidemics of type II diabetes mellitus, insulin resistance, hyperlipidaemia and obesity now prevalent [109] [110] [111] [112] [113] [114] [115] [116] , are just that; epidemics fundamentally caused by viruses that co-opt insulin or leptin or other associated receptors for cell access and generate protein quasispecies that disrupt receptor function? cache = ./cache/cord-318853-mxyxwkhx.txt txt = ./txt/cord-318853-mxyxwkhx.txt === reduce.pl bib === id = cord-314254-9ye8tfvz author = Pfaender, Stephanie title = Natural reservoirs for homologs of hepatitis C virus date = 2014-03-26 pages = extension = .txt mime = text/plain words = 6841 sentences = 322 flesch = 47 summary = To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaciand pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Non-primate hepaciviruses (NPHV) were initially discovered in domestic dogs and subsequently in horses 12, 13 and other diverse and widespread HCV-like viruses have been reported in wild populations of rodents and bats. Furthermore, liver function analyses revealed no indication for hepatic inflammation as c-glutamyl transferase and glutamate dehydrogenase values were within reference range, with the exception of a mildly elevated c-glutamyl transferase New HCV-like viruses in different mammalian hosts Pfaender et al 4 level in one horse. cache = ./cache/cord-314254-9ye8tfvz.txt txt = ./txt/cord-314254-9ye8tfvz.txt === reduce.pl bib === id = cord-314148-5xisw9au author = Hasony, Hassan J. title = Prevalence of human coronavirus antibody in the population of southern iraq date = 2005-12-06 pages = extension = .txt mime = text/plain words = 2761 sentences = 122 flesch = 53 summary = Several reports have analyzed the extent of infections in various populations in America and Europe by estimates of HCV antibodies in sera from patients and volunteers [Bradburne and Somerset, 1972; Candeias et al, 1970; Cavallaro and Monto, 1970 ; Hamre and Beem, 1972; Hendley et al, 1972; Hovi et al, 1979 ; Kaye et al, 1971; McIntosh et al, 1970; Zakstelskaya et al, 19721 . In this study representative viruses from the 229E and OC43 antigenic groups were used in ELISA to measure the antibodies to these viruses in sera collected during the winter from patients and volunteers from the Basrah area of Southern Iraq. 67 random sera were collected from healthy adult volunteers at the Common Cold Unit, Salisbury, before inoculation with any viruses, and tested by ELISA for antibodies to HCV 229E and CV Paris. cache = ./cache/cord-314148-5xisw9au.txt txt = ./txt/cord-314148-5xisw9au.txt === reduce.pl bib === id = cord-307934-84zfabti author = Lai, Chao-Kuen title = Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date = 2014-06-06 pages = extension = .txt mime = text/plain words = 8211 sentences = 465 flesch = 55 summary = Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. Both NS5A and Core proteins are found to be closely associated with and co-transported along the microtubules from the perinuclear region of cells via the LDs and endosomes to the plasma membrane. (A) The HCV-infected cells (at day 10 p.i.) were labeled with antibodies specific for Core protein (red) and NS5A (green) (upper row) or NS4B (green) (lower row). cache = ./cache/cord-307934-84zfabti.txt txt = ./txt/cord-307934-84zfabti.txt === reduce.pl bib === id = cord-343902-hzh3cjzh author = Peel, Michael title = Cyclophilin inhibitors as antiviral agents date = 2013-08-15 pages = extension = .txt mime = text/plain words = 4055 sentences = 184 flesch = 48 summary = Initial reports of CsA inhibiting HIV-1 surfaced in 1988, 25 although the first report specifically implicating CypA involvement in the HIV-1 life cycle was published five years later when it was reported that endogenous CypA colocalizes with the HIV-1 Gag protein in the cytoplasm, binding specifically to a Pro-rich sequence in the HIV-1 capsid domain of Gag. 26 X-ray crystallography later revealed that residues 85-93 of HIV-1 capsid bind to the active site of CypA, 27 and subsequent studies have shown that virions produced in the presence of Gag mutated in the CypA binding region, or under pressure from competitive CypA inhibitors, were less infectious than wild type virions. 36 Further support for CypA being the primary Cyp involved in HCV RNA replication include a demonstration that the catalytic PPIase activity of CypA is required for efficient HCV RNA replication, and the finding that a specific binding between CypA and NS5A is dissociable by addition of CsAbased Cyp inhibitors. cache = ./cache/cord-343902-hzh3cjzh.txt txt = ./txt/cord-343902-hzh3cjzh.txt === reduce.pl bib === id = cord-340220-raqapqg0 author = Potel, Julie title = EWI‐2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry date = 2013-02-16 pages = extension = .txt mime = text/plain words = 11314 sentences = 623 flesch = 56 summary = We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w monoclonal antibodies (mAbs) (Silvie et al., 2006) to analyse the role of tetraspanin web-associated CD81 in HCV infection. Interestingly, as shown for one representative cell clone, cells expressing EWI-2wint exhibited a stronger staining with MT81w, indicating that EWI-2wint modifies CD81 membrane organization, probably by increasing the association of CD81 with the tetraspanin web. To strengthen the hypothesis that EWI-2wint induces a change in CD81 organization at the plasma membrane, we next analysed the membrane dynamics and partitioning of human CD81 (hCD81) molecules in Huh-7 cells expressing or lacking EWI-2wint by single-molecule fluorescence microscopy, which is a method of choice to characterize the diffusion of proteins and lipids in different regions of the plasma membrane (Owen et al., 2009 ). D. Huh-7w7/mCD81 clones expressing pcDNA3.1, EWI-2 or EWI-2wint were stained with MT81 and MT81w mAbs followed by PE-labelled secondary antibody and analysed by flow cytometry. cache = ./cache/cord-340220-raqapqg0.txt txt = ./txt/cord-340220-raqapqg0.txt === reduce.pl bib === id = cord-316703-8kxx3034 author = Parera, Mariona title = Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date = 2012-08-01 pages = extension = .txt mime = text/plain words = 4193 sentences = 220 flesch = 52 summary = The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The target specificity for the MAVS and TRIF cleavage sites was tested by coexpressing them with CHV or HCV NS3/4A protease constructs. coli cells coexpressing the lambda cI repressor with either MAVS or TRIF cleavage site and a CHV NS3/4A construct, lambda phage replicated up to 2,000-fold more efficiently than in cells expressing a CHV protease variant that included a substitution in catalytic residue S139 ( Fig. 3A and 3B). In this study, we tested the ability of CHV NS3/4A protease to specifically cleave the human adaptor proteins MAVS and TRIF. Canine orthologs of human MAVS and TRIF differ in sequence at the cleavage site processed by HCV NS3/4A protease; therefore, they were not tested in this study. cache = ./cache/cord-316703-8kxx3034.txt txt = ./txt/cord-316703-8kxx3034.txt === reduce.pl bib === id = cord-316968-rowoylge author = Zhang, Wenjuan title = Using maximum likelihood method to detect adaptive evolution of HCV envelope protein-coding genes date = 2006 pages = extension = .txt mime = text/plain words = 3532 sentences = 210 flesch = 50 summary = Maximum likelihood (ML) method with codon-substitution models is a powerful statistic tool for detecting amino acid sites under positive selection and adaptive evolution. We analyzed the hepatitis C virus (HCV) envelope protein-coding sequences from 18 general geno/subtypes worldwide, and found 4 amino acid sites under positive selection. The purpose of this study is therefore to use the ML method [9] to infer adaptive evolution and positively selected amino acid sites of HCV envelope protein entire coding sequences containing all 6 HCV genotypes. We took HCV envelope glycoprotein as an example to explore the adaptive evolution driven by immune environment pressure of coding sequences of 27 HCV containing 18 geno/subtypes and found that a number of amino acid sites were under positive selection and ML could be employed for identifying the adaptive evolution of RNA virus on a large scale of genetic diversity. cache = ./cache/cord-316968-rowoylge.txt txt = ./txt/cord-316968-rowoylge.txt === reduce.pl bib === id = cord-323963-whv88ggl author = Fan, Xiaofeng title = Efficient amplification and cloning of near full-length hepatitis C virus genome from clinical samples date = 2006-08-11 pages = extension = .txt mime = text/plain words = 5713 sentences = 303 flesch = 51 summary = Among RNA templates, hepatitis C virus (HCV) represents an excellent example to challenge the potential of LRP technology due to its extensive secondary structures and its difficulty to be readily cultured in vitro. Thus, our LRP protocol could be applied for the amplification of other difficult RNA templates and may facilitate RNA virus research such as linked viral mutations and reverse genetics. In some experiments, we mixed a RT enzyme with Pfu DNA polymerase (Stratagene), a similar strategy as used in long PCR, to improve full-length cDNA synthesis [8] . A representative neighbor-joining (NJ) tree constructed based on HCV E1 domain of 20 clones derived from 9.1 kb LRP product, which was amplified using mixed serum from samples LIV19 and LIV23. A refined long RT-PCR technique to amplify complete viral RNA genome sequences from clinical samples: Application to a novel hepatitis C virus variant of genotype 6 cache = ./cache/cord-323963-whv88ggl.txt txt = ./txt/cord-323963-whv88ggl.txt === reduce.pl bib === id = cord-334493-rt7gqiev author = Ikejiri, Masahiro title = 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents date = 2007-11-15 pages = extension = .txt mime = text/plain words = 4869 sentences = 242 flesch = 61 summary = On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC(50) = 47.2 μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. The resultant residue was purified by silica gel column chromatography (ethyl acetate/hexane, To a stirred solution of 31 (200 mg, 0.56 mmol) in dioxane (1 mL) was added 50% dimethylamine-water solution (8 mL) at room temperature, and the mixture was stirred overnight at the same temperature. cache = ./cache/cord-334493-rt7gqiev.txt txt = ./txt/cord-334493-rt7gqiev.txt === reduce.pl bib === id = cord-349358-leicos9j author = Ketzinel‐Gilad, Mali title = RNA interference for antiviral therapy date = 2006-06-16 pages = extension = .txt mime = text/plain words = 12734 sentences = 684 flesch = 44 summary = During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Likewise, expression vectors of siRNAs specific for two different regions of the WNV genome protected 293T cells from WNV infection, and significantly reduced viral RNA replication and virus production [35] . From the reports on the use of siRNA against human viral pathogens causing acute disease, we could learn that for each specific pathogen infecting a specific cell lineage or tissue, we would probably need to perform an indepth assessment, with proper in vitro and in vivo models, and develop specific delivery systems. The most challenging part of RNAi approaches for chronic viral infections is to design the best delivery method that would facilitate the targeting of the specific organ/cells with the appropriate expression system, for durable intracellular levels of gene-silencing effect. cache = ./cache/cord-349358-leicos9j.txt txt = ./txt/cord-349358-leicos9j.txt === reduce.pl bib === id = cord-326217-ji0njeha author = Saleh, Maged title = Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122 date = 2018-11-27 pages = extension = .txt mime = text/plain words = 4731 sentences = 262 flesch = 48 summary = We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. To assess whether both GSK3 isoforms are required for HCV replication, we silenced GSK3α and / or GSK3β gene expression by transfecting siRNAs and quantified HCV RNA in Huh-7.5 cells harboring HCV subgenomic replicon (Con1) or infectious HCV (Jc1). Given the well-known dependency of HCV on miR-122 (Jopling et al., 2005 (Jopling et al., , 2008 Machlin et al., 2011) and the regulatory circuit between insulin-like growth factor 1 receptor, GSK3β, and miR-122 identified previously (Zeng et al., 2010) , we assessed the effect of GSK3 inhibition on miR-122 expression in Huh-7.5 cells harboring a subgenomic HCV replicon. cache = ./cache/cord-326217-ji0njeha.txt txt = ./txt/cord-326217-ji0njeha.txt === reduce.pl bib === id = cord-337285-t6qr41wc author = Ikeda, Masanori title = Modulation of host metabolism as a target of new antivirals() date = 2007-10-10 pages = extension = .txt mime = text/plain words = 8180 sentences = 466 flesch = 46 summary = Using cell culture systems, several cellular proteins have been identified as effective molecules for HCV RNA replication (Table 1) . [66] reported that lovastatin (LOV), one of the HMG-CoA reductase inhibitors, inhibited HCV RNA replication in HCV replicon-harboring cells. Depletion of the GGPP by statins may inhibit the geranylgeranylation of cellular proteins such as FBL2 and cause the anti-HCV effect in the cells. During the development of IFN therapy for patients with CH-C, the lack of a robust method of HCV RNA replication in cell culture has hampered research into the HCV life cycle and the discovery of potent new anti-HCV reagents. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells cache = ./cache/cord-337285-t6qr41wc.txt txt = ./txt/cord-337285-t6qr41wc.txt === reduce.pl bib === id = cord-321505-m40s6uw9 author = Sakamoto, Naoya title = Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA date = 2007-08-07 pages = extension = .txt mime = text/plain words = 4424 sentences = 253 flesch = 45 summary = Background and Aim: We have reported previously that synthetic small interfering RNA (siRNA) and DNA‐based siRNA expression vectors efficiently and specifically suppress hepatitis C virus (HCV) replication in vitro. Intravenous delivery of the adenovirus expressing shRNA into transgenic mice that can be induced to express HCV structural proteins by the Cre/loxP switching system resulted in specific suppression of virus protein synthesis in the liver. Here, we report that HCV replication was suppressed in vitro by recombinant retrovirus and adenovirus vectors expressing short hairpin RNA (shRNA) and that the delivery of the adenovirus vector to mice in vivo specifically inhibited viral protein synthesis in the liver. These results indicated that the decrease in luciferase activities was due to specific suppressive effects of shRNA on expression of HCV genomic RNA and the viral proteins, and not due to non-specific effects caused by the delivery of shRNA or to toxicity of the adenovirus vectors. cache = ./cache/cord-321505-m40s6uw9.txt txt = ./txt/cord-321505-m40s6uw9.txt === reduce.pl bib === id = cord-332422-s15o0hie author = Belouzard, Sandrine title = Hepatitis C virus entry into the hepatocyte date = 2011-11-07 pages = extension = .txt mime = text/plain words = 6987 sentences = 365 flesch = 47 summary = HCV envelope glycoproteins are key determinants of HCV entry with a role in receptor binding and in mediating the fusion process between the viral envelope and an endosomal host cell membrane. Furthermore, functional non-infectious and capsidless structures, called subviral particles, can be produced when the HCV envelope glycoproteins are expressed alone in lipoprotein producing cell lines [8] , supporting the idea that HCV envelope glycoproteins play an active role during the budding process. The role of SRB1 in HCV entry was first suggested by its ability to mediate soluble E2 binding [13] and it was later confirmed by the inhibition of HCV infection with anti-SRB1 antibodies and by silencing of the protein in hepatoma cells (reviewed in [5, 26, 27] ). Virus-associated lipoproteins are likely playing a role in the early phase of HCV entry, whereas envelope glycoproteins are believed to take the lead after this initial step. cache = ./cache/cord-332422-s15o0hie.txt txt = ./txt/cord-332422-s15o0hie.txt === reduce.pl bib === id = cord-333331-ddcz7zck author = Yang, Jin title = Detection of hepatitis C virus by an improved loop-mediated isothermal amplification assay date = 2011-05-12 pages = extension = .txt mime = text/plain words = 5207 sentences = 245 flesch = 54 summary = An improved, sensitive, specific, and rapid one-step reverse transcription loop-mediated isothermal amplification (LAMP) assay targeting the 5′ untranslated region (UTR) was developed to detect hepatitis C virus (HCV) infection. A variety of molecular diagnostic assays, such as reverse transcriptase PCR [12] , nucleic-acid-sequence-based amplification [13] , transcription-mediated amplification [29] , branched-chain DNA assay [26] , and in-house realtime PCR [8] , have been developed for the detection of HCV RNA. Confirmed cases of HCV infection were verified by a positive result in an enzyme-linked immunosorbent assay (Kehua Bio-engineering, Shanghai, China) for antibodies against HCV or a quantitative real-time PCR for HCV RNA. Given that the sensitivity of the AP-LAMP assay for detecting HCV is higher than that of the pre-LAMP method, the pathway of AP-based amplification was investigated. Reverse transcription-loop-mediated isothermal amplification assay for rapid detection of hepatitis E virus cache = ./cache/cord-333331-ddcz7zck.txt txt = ./txt/cord-333331-ddcz7zck.txt === reduce.pl bib === id = cord-332747-u46xryoo author = Mingorance, Lidia title = Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation date = 2018-09-18 pages = extension = .txt mime = text/plain words = 10355 sentences = 485 flesch = 37 summary = To determine which aspects of the HCV replication cycle are limited by lipin1 silencing, single cycle infection experiments were conducted by inoculating control and lipin1-deficient cell cultures at MOI 10 with genotype 2a D183 virus. Once cultures reached >95% of HCV-positive cells, they were transduced with lentiviral vectors expressing control, HCV RNA-targeting or LPIN1-specific shRNAs. At day 7 post-transduction, cells were split and samples of the cells and supernatants were collected 24 hours later to determine infectious virus production rate by infectivity titration HCV (C) and RNA levels by RT-qPCR (D). This reduced abundance is illustrated by a significant reduction in the fraction of cells displaying vesicular structures in lipin1-deficient cell cultures (Fig 7H) despite comparable transfection efficiency and viral protein expression levels, indicating that lipin1 may be required in a critical step leading to formation of the HCV-induced vesicular compartment. cache = ./cache/cord-332747-u46xryoo.txt txt = ./txt/cord-332747-u46xryoo.txt === reduce.pl bib === id = cord-327135-4c2flue4 author = Chinnaswamy, S title = Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections date = 2016-06-09 pages = extension = .txt mime = text/plain words = 9813 sentences = 499 flesch = 48 summary = Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. Three independent groups conducted genome-wide association studies (GWASs) involving treatment response to chronic hepatitis C virus (HCV) infections, in three different geographical regions of the world, and reported that single-nucleotide polymorphisms (SNPs) in the IFNL locus (Figure 1 ), had strong association with treatment-induced HCV clearance irrespective of ethnicity and geographical location of the hosts. 49 In stark contrast, a dominant model of inheritance (of the non-beneficial IFNL SNP minor allele) has consistently given the best explanation on the observed phenotypes in association studies with both spontaneous clearance and IFN-based treatment response in chronic HCV infections. cache = ./cache/cord-327135-4c2flue4.txt txt = ./txt/cord-327135-4c2flue4.txt === reduce.pl bib === id = cord-345898-a6vt8kso author = Ren, Linzhu title = Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses date = 2016-01-04 pages = extension = .txt mime = text/plain words = 6000 sentences = 289 flesch = 38 summary = There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. An RVP is a type of virus-like particle (VLP) composed of viral structural proteins and a self-replicating replicon RNA containing a reporter gene [17, 63] . However, when the cells were infected with the specific virus, the viral RdRp was provided by the virus and the defective replicon was activated, resulting in high-level expression of the reporter gene, which could be easily examined [44] . However, when the cells were infected with the specific virus, the viral RdRp was provided by the virus and the defective replicon was activated, resulting in high-level expression of the reporter gene, which could be easily examined [44] . Development of Dengue type-2 virus replicons expressing GFP reporter gene in study of viral RNA replication cache = ./cache/cord-345898-a6vt8kso.txt txt = ./txt/cord-345898-a6vt8kso.txt === reduce.pl bib === id = cord-335085-7pxkhgbq author = Dessau, R. B. title = Coronaviruses in spinal fluid of patients with acute monosymptomatic optic neuritis date = 2009-01-29 pages = extension = .txt mime = text/plain words = 2145 sentences = 130 flesch = 64 summary = Material and methods ‐ Spinal fluids from 37 patients with AMON and 15 surgical control patients with protrusion of the intervertebral disk were assayed with a nested multiplex polymerase chain reaction with primers specific for human coronaviruses strain (HCV) 229E and OC43. To investigate the possibility of an infection with human coronaviruses (HCV) in early MS and as a possible cause of AMON we have analyzed cerebrospinal fluid (CSF) from patients with AMON using reverse transcriptase reaction and the polymerase chain reaction (RT-PCR) applying primers specific for HCV. CSF from 4 patients and 1 control ( Table 2) were positive on nested RT-PCR using the HCV-229E primers and all samples were negative with the HCV-OC43 primers. HCV-229E RNA was found in the CSF by RT-PCR in 4 of 37 patients with AMON and in 1 of 15 controls. cache = ./cache/cord-335085-7pxkhgbq.txt txt = ./txt/cord-335085-7pxkhgbq.txt === reduce.pl bib === id = cord-341071-nwrl1qws author = Berzal-Herranz, Alfredo title = Two Examples of RNA Aptamers with Antiviral Activity. Are Aptamers the Wished Antiviral Drugs? date = 2020-07-22 pages = extension = .txt mime = text/plain words = 5442 sentences = 287 flesch = 44 summary = Pharmaceuticals 2020, 13 Elucidating the function of each RNA domain and their modus operandi would provide an excellent scenario to address the control of infections caused by RNA viruses, broadening beyond proteins the repertoire of potential target candidates to fight viral diseases. Elucidating the function of each RNA domain and their modus operandi would provide an excellent scenario to address the control of infections caused by RNA viruses, broadening beyond proteins the repertoire of potential target candidates to fight viral diseases. Consequently, in contrast to other nucleic acid based strategies (ribozymes, antisense oligonucleotides, siRNA, among others), aptamers are postulated as excellent candidates to directly interfere with the functioning of essential structural domains of viral RNA genomes. Herein, we present an extension of a video we communicated at the 5th ECMC describing two examples of selection and characterization of aptamers targeting essential structural domains of respective viral RNA genomes, performed in our laboratory [21] . cache = ./cache/cord-341071-nwrl1qws.txt txt = ./txt/cord-341071-nwrl1qws.txt === reduce.pl bib === id = cord-350600-73q8mve4 author = Myint, S. title = Detection of human coronavirus 229E in nasal washings using RNA:RNA hybridization date = 2005-12-09 pages = extension = .txt mime = text/plain words = 1996 sentences = 126 flesch = 61 summary = A method is described for the detection of human coronavirus 229E (HCV 229E) in nasal washings using RNA:RNA filter hybridization. In this paper we describe a specific and sensitive test to detect one of these major groups, HCV 2293, in nasal washings. Briefly, using a method based on that of Gubler and Hoffmann [19831, cDNAs were generated from HCV 2293 RNA isolated from infected C16 cells [Phillpotts, 19831. The results of virus titration and probing of nasal washings from seven volunteers are presented in Table I . Three of the seven volunteers suffered a cold, and all three volunteers had detectable coronavirus RNA in their nasal washings. The results we have obtained show that the detection of HCV 2293 infection by nucleic acid hybridisation is a reliable and specific method. Hybridisation to known quantities of HCV 2293 RNA showed that less than 1 ng of virus-specific RNA from C16 cells infected with HCV 2293 could be detected. cache = ./cache/cord-350600-73q8mve4.txt txt = ./txt/cord-350600-73q8mve4.txt === reduce.pl bib === id = cord-314567-purplsjn author = Fernández-Ponce, Cecilia title = Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells date = 2018-01-04 pages = extension = .txt mime = text/plain words = 7978 sentences = 382 flesch = 41 summary = HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. As studies using the whole virus do not allow for the elucidation of the specific molecular mechanisms in which each protein is implicated, in this work, we focused on a single viral protein, showing that in CD4 + T cells, HCV core protein mostly localizes in the nucleus and specifically in the nucleolus where it is greatly enriched. cache = ./cache/cord-314567-purplsjn.txt txt = ./txt/cord-314567-purplsjn.txt === reduce.pl bib === id = cord-351365-dc9t3vh3 author = Todt, Daniel title = Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date = 2016-10-13 pages = extension = .txt mime = text/plain words = 6318 sentences = 320 flesch = 40 summary = Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. Figure 1 provides an overview of a selection of RNA viruses against which RBV was shown to be active: hepatitis C virus (HCV, Flaviviridae), dengue virus (DENV, Flaviviridae), respiratory syncytial virus (RSV, Paramyxoviridae), influenza A and B virus (Orthomyxoviridae), chikungunya virus (CHIKV, Togaviridae), poliovirus (Picornaviridae), Hantaan virus (Bunyaviridae), and Lassa virus (Arenaviridae) [28, 29] ( Figure 1 ). Furthermore, mechanisms on the virus itself were described by inhibition of the capping efficiency, the viral polymerase, and a mutagenic effect on newly synthesized RNA genomes. A Mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients cache = ./cache/cord-351365-dc9t3vh3.txt txt = ./txt/cord-351365-dc9t3vh3.txt === reduce.pl bib === id = cord-023354-f2ciho6o author = nan title = TUESDAY PLENARY SESSION 3 TUESDAY: POSTERS date = 2005-06-08 pages = extension = .txt mime = text/plain words = 130046 sentences = 7333 flesch = 54 summary = • enhancement of automation/computerisation; • process control to provide an 'error-free pathway'; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody 'combi' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas' disease infection (for retrieval of otherwise wasted blood); • European Union's in vitro diagnostics directive: this has caused some problems and reduced flexibility. cache = ./cache/cord-023354-f2ciho6o.txt txt = ./txt/cord-023354-f2ciho6o.txt === reduce.pl bib === === reduce.pl bib === id = cord-330110-pamxy4av author = Teissier, Elodie title = Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date = 2011-01-25 pages = extension = .txt mime = text/plain words = 9268 sentences = 438 flesch = 48 summary = Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. By combining surface plasmon resonance, fluorescence and NMR spectroscopy approaches, we showed that Arb directly interacts with the phospholipid membrane interface, with an affinity in the micromolar range, comparable to the concentration inhibiting HCVpp membrane fusion by 50% (IC50). Altogether our results demonstrate that Arb interacts with the polar head of phospholipid membranes and protein motifs enriched in aromatic residues, suggesting that the inhibitory activity of Arb on HCV entry and fusion could involve both types of interactions. Conversely, Arb inhibition of HCVpp membrane fusion, as assessed by a in vitro model system where the only proteins present are the viral glycoproteins, could merely reflect the interaction of Arb on lipids and/or on motifs present in HCV glycoproteins of any genotype. cache = ./cache/cord-330110-pamxy4av.txt txt = ./txt/cord-330110-pamxy4av.txt === reduce.pl bib === id = cord-347992-coby2m6e author = Marton, Soledad title = In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date = 2010-06-28 pages = extension = .txt mime = text/plain words = 10035 sentences = 535 flesch = 45 summary = Although ribozymes and DNAzymes have been extensively assayed as potential therapeutic agents, and different clinical trials have already tested their efficiency against various diseases [49] [50] [51] [52] , very few reports have described the direct application of in vitro selection strategies in the development of potentially therapeutic catalytic nucleic acids. Molecular studies have shown that this aptamer binds to the cell surface protein nucleolin and inhibits the activity of NF-KB, a ubiquitous transcription factor, through intracellular complex formation [108] . In a different approach, SELEX has been performed with the E2F1 protein to find in vitro selected RNA aptamers that bind to and inhibit E2F activity. Astier-Gi's group described the characterization of two DNA aptamers (27v and 127v) that specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B), inhibiting its activity in vitro [146] . In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins cache = ./cache/cord-347992-coby2m6e.txt txt = ./txt/cord-347992-coby2m6e.txt === reduce.pl bib === id = cord-344084-z4t2wkgk author = Ellwanger, Joel Henrique title = Beyond HIV infection: neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases date = 2020-05-30 pages = extension = .txt mime = text/plain words = 15735 sentences = 840 flesch = 45 summary = The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. In agreement with studies showing that CCR5Δ32 homozygous genotype is a risk factor for symptomatic WNV infection in humans, Ccr5-/-WNV-infected mice showed a reduced capacity of viral control, increased disease severity, impaired leukocyte trafficking towards the brain, and high mortality rates than Ccr5 wild-type mice. In conclusion, although tissue analysis and evidence obtained in vitro suggest that the CCR5 is potentially involved in the pathogenesis of HPV, most studies point to a lack of involvement of CCR5Δ32 in susceptibility to HPV infection or HPV-associated diseases. cache = ./cache/cord-344084-z4t2wkgk.txt txt = ./txt/cord-344084-z4t2wkgk.txt === reduce.pl bib === id = cord-324984-ojrpsdt9 author = Ji, Xingyue title = Medicinal chemistry strategies toward host targeting antiviral agents date = 2020-02-14 pages = extension = .txt mime = text/plain words = 16814 sentences = 825 flesch = 43 summary = In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. 3 Altogether, targeting host factors is a very promising strategy with possibility to address the critical challenges faced with the DAAs. In this review, we summarize the recent advances made in HTAs from a medicinal chemistry standpoint, and the host targets are generally classified into three different categories based on the development stage of their corresponding inhibitors/modulators, namely the ones which reached Food and Drug Administration (FDA) approval, that have entered clinical trials and those in preclinical studies. cache = ./cache/cord-324984-ojrpsdt9.txt txt = ./txt/cord-324984-ojrpsdt9.txt === reduce.pl bib === id = cord-007890-bie1veti author = nan title = ECC-4 Abstracts date = 2002-04-16 pages = extension = .txt mime = text/plain words = 85992 sentences = 5665 flesch = 50 summary = Effects of Interferon alpha plus ribavirine therapy on frequencies of HCV, HIV and CMV specific CD4-T-cell responses in peripheral blood of HIV/HCV coinfected patients after 6 months of treatment SoA9.5 Methods: Two groups of patients with chronic HCV infection were studied: 26 HIV coinfected progressors with antiretroviral therapy and 13 HIV-negative controls. In order to assess the local temporal trend of antibiotic sensitivity of the most common urinary tract bacterial pathogen, all urine-cultured Escherichia coli isolates were reviewed as to susceptibility profile, and specimen source (community-versus hospital-acquired infection). Methods: A total of 87 penicillin resistant clinical strains isolated from patients at Hacettepe Children's Hospital, Ankara, Turkey between 1999 and 2001 were tested for their in vitro susceptibility to various antibiotics that are commonly used in the treatment of respiratory tract infections. cache = ./cache/cord-007890-bie1veti.txt txt = ./txt/cord-007890-bie1veti.txt === reduce.pl bib === id = cord-342676-ykog278j author = Stewart, H. title = Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date = 2016-03-14 pages = extension = .txt mime = text/plain words = 6858 sentences = 338 flesch = 46 summary = To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We wished to investigate the possibility that similar specific secondary structures are present within HCV RNAs destined for packaging, and whether their interactions with Core cooperatively drive the RNA encapsidation and nucleocapsid assembly processes. A mutant genome unable to form such structures displays impaired viral infectivity whilst RNA replication is unaffected, indicating these motifs may interact specifically with Core. Role of RNA structures in genome terminal sequences of the hepatitis C virus for replication and assembly cache = ./cache/cord-342676-ykog278j.txt txt = ./txt/cord-342676-ykog278j.txt === reduce.pl bib === id = cord-023346-8sqbqjm1 author = nan title = MONDAY: POSTERS date = 2005-06-08 pages = extension = .txt mime = text/plain words = 130043 sentences = 7330 flesch = 54 summary = • enhancement of automation/computerisation; • process control to provide an 'error-free pathway'; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody 'combi' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas' disease infection (for retrieval of otherwise wasted blood); • European Union's in vitro diagnostics directive: this has caused some problems and reduced flexibility. cache = ./cache/cord-023346-8sqbqjm1.txt txt = ./txt/cord-023346-8sqbqjm1.txt === reduce.pl bib === id = cord-343963-99rd3o79 author = Wong, Mun-Teng title = Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date = 2014-12-29 pages = extension = .txt mime = text/plain words = 17253 sentences = 1074 flesch = 42 summary = 13, 14 Upon infection by viruses such as HCV, viral RNA is first sensed by cellular pattern recognition receptors (PRRs), and the PRR-mediated recruitment of adaptor proteins and the activation of downstream signaling lead to IFN production. First, we briefly discuss the signaling triggered by the retinoic acid-inducible gene 1-like receptor (RLR) and the Toll-like receptor (TLR), which leads to type I IFN synthesis and IFN-mediated signaling pathway activation, resulting in the expression of a variety of effector ISGs. We also summarize the strategies that HCV uses to escape IFN antiviral surveillance. 156 demonstrated that HCVinduced SG formation is IFN-and PKR-dependent and is inversely correlated with the induction of ISG proteins, such as myxovirus resistance gene A (MxA) and Ub-like (UBL)specific protease 18 (USP18), in HCV-infected cells without affecting the mRNA levels of these ISGs. Furthermore, the SG proteins TIA-1, TIAR and G3BP1 have been shown to play a critical role in HCV replication and infectious virus production. cache = ./cache/cord-343963-99rd3o79.txt txt = ./txt/cord-343963-99rd3o79.txt === reduce.pl bib === id = cord-350640-sz6xj5o3 author = Menzel, Nicolas title = MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles date = 2012-07-26 pages = extension = .txt mime = text/plain words = 10059 sentences = 549 flesch = 49 summary = When transfecting our infectious firefly luciferase reporter virus genome Luc-Jc1 [14] into highly permissive Huh-7.5 human hepatoma cells [15] cultured in the presence or absence of serum, we measured comparable levels of luciferase activity 4 to 48 h after transfection ( Figure S1A ). Among the inhibitors tested, U0126 a selective inhibitor of the MAPK/ERK pathway, substantially decreased the production of infectious virus particles as is evident from the dose-dependent reduction of luciferase activity in the inoculated cells ( Figure 1B) . To investigate if PLA2G4A activity is relevant for the production of infectious HCV particles we treated Luc-Jc1 transfected cells with pyrrolidine-2 (Py-2), a specific inhibitor of this type of phospholipase [22, 23] . Irrespective of culturing these cells in the presence or absence of serum, we observed a strong and dose-dependent inhibition of production of infectious particles resulting in a more than 100-fold reduction of luciferase transduction at 5 and 20 mM of Py-2, respectively ( Figure 2B ). cache = ./cache/cord-350640-sz6xj5o3.txt txt = ./txt/cord-350640-sz6xj5o3.txt === reduce.pl bib === id = cord-347319-lcuma3eh author = Ashfaq, Usman A title = Lysosomotropic agents as HCV entry inhibitors date = 2011-04-12 pages = extension = .txt mime = text/plain words = 2579 sentences = 146 flesch = 50 summary = HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. To investigate the antiviral effect of LA (Chloroquine and NH(4)Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. For antiviral screening of Chloroquine and NH(4)Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. We therefore tested the infectivity of HCVpp after treatment of target cells with different concentrations of Chloroquine and NH 4 Cl. HCVpp of 1a and 3a genotype demonstrated dose-dependent inhibition in the presence of Chloroquine and NH 4 Cl. Chloroquine and NH 4 Cl showed greater than 50% reduction of virus infectivity at 50 μM and 10 mM concentration respectively, suggesting a pH-sensitive route of virus entry (Figure 2a and 2b ). cache = ./cache/cord-347319-lcuma3eh.txt txt = ./txt/cord-347319-lcuma3eh.txt === reduce.pl bib === id = cord-347710-ff64y6ef author = Wan, Qianya title = Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date = 2020-07-13 pages = extension = .txt mime = text/plain words = 36567 sentences = 2487 flesch = 46 summary = hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. 6, 13 It is well known that Hsp90 not only interacts and contributes to RNA polymerase assembly and nuclear import of some (−) ssRNA viruses (e.g., PB2 of influenza virus), but plays crucial roles in the folding process of viral capsid proteins and virion assemblies as well. 17, 18 As a critical component of cellular protein surveillance, the ATP-dependent molecular chaperone protects cells from damage caused by stress and takes part in a number of folding processes, including folding of newly synthesized polypeptides, recognition and refolding of misfolded or aggregated proteins, solubilization or degradation of proteins, transporting proteins, assembly or disassembly of oligomeric protein complexes, and the regulation of certain natively folded proteins. cache = ./cache/cord-347710-ff64y6ef.txt txt = ./txt/cord-347710-ff64y6ef.txt === reduce.pl bib === id = cord-342901-ca2xxkb2 author = Lloyd, Richard E. title = Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses date = 2015-05-31 pages = extension = .txt mime = text/plain words = 16221 sentences = 823 flesch = 50 summary = Though PTB was the first, a wide spectrum of factors, largely nuclear RBPs, have also been proposed as poliovirus ITAFs, including Lupus autoantigen (La) (Meerovitch et al., 1993 (Meerovitch et al., , 1989 , poly(rC)binding proteins (PCBPs) (Blyn et al., 1996; Gamarnik and Andino, 1997) , upstream of N-ras (UNR) (Anderson et al., 2007; Boussadia et al., 2003; Hunt et al., 1999) , SRp20 (Bedard et al., 2007) and glycyl-tRNA synthetase (GARS) (Andreev et al., 2012) (Table 1 ). In addition, certain ITAFs play crucial roles in regulating the conversion of translation-competent genomic RNAs into replicationcompetent RNAs. PTB was known as a nuclear splicing factor when its role as an ITAF of poliovirus and EMCV was discovered; a classic hijacked nuclear protein pressed into a new role required for the virus. cache = ./cache/cord-342901-ca2xxkb2.txt txt = ./txt/cord-342901-ca2xxkb2.txt === reduce.pl bib === id = cord-000083-3p81yr4n author = nan title = Poster Exhibition date = 2009-01-31 pages = extension = .txt mime = text/plain words = 112815 sentences = 7542 flesch = 56 summary = R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit. cache = ./cache/cord-000083-3p81yr4n.txt txt = ./txt/cord-000083-3p81yr4n.txt === reduce.pl bib === id = cord-022888-dnsdg04n author = nan title = Poster Sessions date = 2009-08-19 pages = extension = .txt mime = text/plain words = 188640 sentences = 9313 flesch = 45 summary = Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cache = ./cache/cord-022888-dnsdg04n.txt txt = ./txt/cord-022888-dnsdg04n.txt === reduce.pl bib === id = cord-023364-ut56gczm author = nan title = EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS date = 2005-06-08 pages = extension = .txt mime = text/plain words = 130049 sentences = 7334 flesch = 54 summary = • enhancement of automation/computerisation; • process control to provide an 'error-free pathway'; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody 'combi' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas' disease infection (for retrieval of otherwise wasted blood); • European Union's in vitro diagnostics directive: this has caused some problems and reduced flexibility. cache = ./cache/cord-023364-ut56gczm.txt txt = ./txt/cord-023364-ut56gczm.txt === reduce.pl bib === id = cord-009567-osstpum6 author = nan title = Abstracts Oral date = 2008-04-23 pages = extension = .txt mime = text/plain words = 131214 sentences = 7728 flesch = 53 summary = Introduction: Previously, it has been demonstrated that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during cardiac rejection, suggesting infiltration of regulatory T cells in the transplanted organ during an allogeneic response. Efficacy and safety parameters assessed at follow-up included: acute rejection; patient and graft survival; renal function, vital signs, basic lab results and immunosuppressive regimen for the patients 10 years after completion of the original study. We analyzed, for the first time, the expression of TLR4 in PBMC from kidney recipients with contrasted situations: operational tolerance and chronic immune-mediated rejection (Banff 2005), compared to patients with normal histology and stable graft function, non transplant patients with renal failure and healthy volunteers. cache = ./cache/cord-009567-osstpum6.txt txt = ./txt/cord-009567-osstpum6.txt === reduce.pl bib === id = cord-350571-6tapkjb6 author = nan title = 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016 date = 2017-01-10 pages = extension = .txt mime = text/plain words = 106013 sentences = 6203 flesch = 48 summary = Possible solutions might be to use shared communication tools like Internet based communication programs and to introduce the patient as a participant at the IMRs. Please specify your abstract type: Research abstract Background and objective: International good pharmacy practice guidelines describe how pharmacists should counsel the patients about their medicines, offer additional services where needed, and intervene at drug related problems. Please specify your abstract type: Descriptive abstract (for projects) Background and objective: In order to improve the medication reconciliation and to implement training programs for the medical team in an associated to general hospital nursing (ASNH) home we measured the discrepancies between pharmacy registered treatments (PRT) and medical prescriptions (MP), and we analysed potentially inappropriate prescriptions according to ''American Geriatrics Society 2015 Beers Criteria'' and ''STOPP-START 2014 criteria. cache = ./cache/cord-350571-6tapkjb6.txt txt = ./txt/cord-350571-6tapkjb6.txt === reduce.pl bib === id = cord-010092-uftc8inx author = nan title = Abstract of 29th Regional Congress of the ISBT date = 2019-06-07 pages = extension = .txt mime = text/plain words = 233304 sentences = 13171 flesch = 54 summary = Prospective testing of blood donations in endemic areas of the U.S. revealed 0.38% of donors were positive for Babesia DNA or antibodies (Moritz, NEJM, 2016) Aims: -To report results of ongoing Babesia clinical trial -To explain significance of Babesia as a TT infection Methods: In cobas â Babesia for use on the cobas â 6800/8800 Systems, is a qualitative polymerase chain reaction nucleic acid amplification test, developed to detect in whole blood (WB) donor samples the 4 Babesia species that cause human disease: B. In sensitivity analyses, there were two discrepant results for HIV testing, three for HCV, and five for anti-HBc. Summary/Conclusions: Elecsys â infectious disease parameters on the cobas e 801 analyser demonstrate high specificity/sensitivity for screening first-time blood donor samples, with similar clinical performance to other commercially available assays. cache = ./cache/cord-010092-uftc8inx.txt txt = ./txt/cord-010092-uftc8inx.txt === reduce.pl bib === id = cord-010119-t1x9gknd author = nan title = Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date = 2017-09-04 pages = extension = .txt mime = text/plain words = 230193 sentences = 13234 flesch = 55 summary = Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). cache = ./cache/cord-010119-t1x9gknd.txt txt = ./txt/cord-010119-t1x9gknd.txt ===== Reducing email addresses cord-000830-jiy4cp4n cord-020010-q58x6xb0 cord-017948-fqhl1qb4 cord-284693-mgpxnnk0 Creating transaction Updating adr table ===== Reducing keywords cord-000638-ss1435el cord-000174-mgj9zfft cord-003407-f5v3hhr8 cord-000008-3dgjv0x1 cord-001421-6t5puo6p cord-000833-m6abyuvx cord-000786-ofpcgxce cord-000830-jiy4cp4n cord-001834-6xf4o3oy cord-003158-mhlqnj52 cord-000473-jpow6iw1 cord-006061-z9r5htm9 cord-006436-61mgtbj4 cord-006129-5rog0s98 cord-005617-bxbogskm cord-007236-8hiymqyb cord-003993-3bozjfv7 cord-001848-idmj2d7p cord-002410-2zi5iv2t cord-007305-pkjfnhro cord-002369-shk4n8f6 cord-009263-w8bmmgtj cord-011182-nbtfb39r cord-006856-b1w25ob5 cord-016343-wc3i54fc cord-015372-76xvzvdg cord-017506-t86v3zw3 cord-018220-8m11ig06 cord-013244-d6saaiu9 cord-002774-tpqsjjet cord-010273-0c56x9f5 cord-010088-s9tfvtao cord-011026-iapgkz0p cord-026112-58sa5z03 cord-018785-tcr5xlf8 cord-013176-6ckuya1w cord-030361-0tepkjdl cord-258234-qn8xp4v9 cord-264713-38dlh3wg cord-253768-y35m3vh1 cord-261287-l4649du3 cord-255781-55zrmgxq cord-284904-qw1ig2v4 cord-264936-3posyr5n cord-015941-4fz79wzf cord-005138-u2lwgyyf cord-017764-h1w9gbxk cord-253825-d9borky8 cord-023017-k6edtg58 cord-281389-sht0yx4a cord-256036-gd53s4dv cord-020010-q58x6xb0 cord-024003-698d15gk cord-265588-1tcaleeo cord-017948-fqhl1qb4 cord-023033-tgt69ir6 cord-264326-teahway7 cord-256769-flfycl7i cord-270498-hh6h50t2 cord-274080-884x48on cord-260099-mthwab4p cord-280330-ibvbowl0 cord-027860-s97hdhh6 cord-259916-gr6v098c cord-276364-zyw5aukk cord-271635-tydlyc1q cord-273555-i1d4quos cord-284978-vh1x6pg9 cord-281883-l9yshyc7 cord-022380-49oti4zg cord-265592-r8nlef0h cord-267867-q52nvn0n cord-268467-btfz6ye8 cord-285505-8norumv6 cord-269194-b1wlr3t7 cord-279202-iyteg4h9 cord-263433-oldy0gta cord-284549-edliu3it cord-271091-ffn59sgf cord-256118-gxhhwqdd cord-281941-97t45w73 cord-284693-mgpxnnk0 cord-285868-fz5utxss cord-280878-1kt51viz cord-269294-vx7xr80t cord-265005-e6rpryrh cord-266738-8xx1xm2d cord-292940-kg1rl6rb cord-286719-1xjmlwqr cord-300642-c7adeis1 cord-291321-ao80xk11 cord-289321-ahl46ql9 cord-294842-aesiff1f cord-284551-j0nooxmd cord-299747-qovrstak cord-293790-7hyelm88 cord-293653-u2qrxq6t cord-298033-kzdp9edn cord-293646-d4qcckh1 cord-302295-nblmshni cord-299719-bvdsz626 cord-303189-ktl4jw8v cord-284376-plwyjhl8 cord-293857-o8rlqsq5 cord-298736-9bvyp21d cord-305303-82n96ukr cord-307556-k2lavvca cord-305039-grsv06j7 cord-286334-d9v5xtx7 cord-305263-fgwf6wy3 cord-300154-3p7tjp5j cord-307817-2vy28i4m cord-305393-96mrxt8a cord-312080-pu6m4qad cord-305085-bv7udg9k cord-306934-29ljbl7g cord-311823-85wj08gr cord-321230-b5a1z14w cord-314753-xflhxb13 cord-321053-lgae22f8 cord-319754-5isw53wl cord-325989-nf6ouaq3 cord-324559-p92y5er2 cord-324054-d71rj29o cord-317595-siwzjeea cord-318853-mxyxwkhx cord-314254-9ye8tfvz cord-314148-5xisw9au cord-307934-84zfabti cord-343902-hzh3cjzh cord-340220-raqapqg0 cord-316703-8kxx3034 cord-316968-rowoylge cord-349358-leicos9j cord-323963-whv88ggl cord-334493-rt7gqiev cord-326217-ji0njeha cord-321505-m40s6uw9 cord-337285-t6qr41wc cord-332747-u46xryoo cord-332422-s15o0hie cord-345898-a6vt8kso cord-327135-4c2flue4 cord-333331-ddcz7zck cord-335085-7pxkhgbq cord-341071-nwrl1qws cord-350600-73q8mve4 cord-314567-purplsjn cord-351365-dc9t3vh3 cord-023354-f2ciho6o cord-347992-coby2m6e cord-321773-5fw9abzl cord-330110-pamxy4av cord-344084-z4t2wkgk cord-324984-ojrpsdt9 cord-023346-8sqbqjm1 cord-007890-bie1veti cord-343963-99rd3o79 cord-342676-ykog278j cord-347319-lcuma3eh cord-350640-sz6xj5o3 cord-342901-ca2xxkb2 cord-347710-ff64y6ef cord-000083-3p81yr4n cord-023364-ut56gczm cord-022888-dnsdg04n cord-350571-6tapkjb6 cord-010119-t1x9gknd cord-009567-osstpum6 cord-010092-uftc8inx Creating transaction Updating wrd table ===== Reducing urls cord-003407-f5v3hhr8 cord-000174-mgj9zfft cord-000473-jpow6iw1 cord-003993-3bozjfv7 cord-006129-5rog0s98 cord-002369-shk4n8f6 cord-011182-nbtfb39r cord-018220-8m11ig06 cord-013244-d6saaiu9 cord-010088-s9tfvtao cord-264936-3posyr5n cord-253825-d9borky8 cord-281389-sht0yx4a cord-024003-698d15gk cord-281883-l9yshyc7 cord-263433-oldy0gta cord-284549-edliu3it cord-269294-vx7xr80t cord-266738-8xx1xm2d cord-266105-8avkjc84 cord-284551-j0nooxmd cord-298033-kzdp9edn cord-284376-plwyjhl8 cord-286334-d9v5xtx7 cord-305263-fgwf6wy3 cord-300154-3p7tjp5j cord-314753-xflhxb13 cord-324559-p92y5er2 cord-317595-siwzjeea cord-318853-mxyxwkhx cord-316703-8kxx3034 cord-316968-rowoylge cord-326217-ji0njeha cord-333331-ddcz7zck cord-332747-u46xryoo cord-314567-purplsjn cord-327135-4c2flue4 cord-023354-f2ciho6o cord-344084-z4t2wkgk cord-023346-8sqbqjm1 cord-343963-99rd3o79 cord-347710-ff64y6ef cord-023364-ut56gczm cord-022888-dnsdg04n cord-350571-6tapkjb6 cord-010092-uftc8inx cord-010119-t1x9gknd Creating transaction Updating url table ===== Reducing named entities cord-000008-3dgjv0x1 cord-000174-mgj9zfft cord-003407-f5v3hhr8 cord-000638-ss1435el cord-000833-m6abyuvx cord-000786-ofpcgxce cord-001421-6t5puo6p cord-000830-jiy4cp4n cord-000473-jpow6iw1 cord-003158-mhlqnj52 cord-001834-6xf4o3oy cord-006061-z9r5htm9 cord-006436-61mgtbj4 cord-005617-bxbogskm cord-006129-5rog0s98 cord-007236-8hiymqyb cord-003993-3bozjfv7 cord-001848-idmj2d7p cord-002410-2zi5iv2t cord-007305-pkjfnhro cord-009263-w8bmmgtj cord-002369-shk4n8f6 cord-011182-nbtfb39r cord-018220-8m11ig06 cord-017506-t86v3zw3 cord-016343-wc3i54fc cord-013244-d6saaiu9 cord-015372-76xvzvdg cord-006856-b1w25ob5 cord-010273-0c56x9f5 cord-011026-iapgkz0p cord-026112-58sa5z03 cord-030361-0tepkjdl cord-018785-tcr5xlf8 cord-002774-tpqsjjet cord-010088-s9tfvtao cord-013176-6ckuya1w cord-258234-qn8xp4v9 cord-264713-38dlh3wg cord-253768-y35m3vh1 cord-261287-l4649du3 cord-284904-qw1ig2v4 cord-255781-55zrmgxq cord-264936-3posyr5n cord-015941-4fz79wzf cord-005138-u2lwgyyf cord-017764-h1w9gbxk cord-253825-d9borky8 cord-256036-gd53s4dv cord-281389-sht0yx4a cord-265588-1tcaleeo cord-024003-698d15gk cord-017948-fqhl1qb4 cord-264326-teahway7 cord-023033-tgt69ir6 cord-256769-flfycl7i cord-270498-hh6h50t2 cord-260099-mthwab4p cord-280330-ibvbowl0 cord-259916-gr6v098c cord-020010-q58x6xb0 cord-274080-884x48on cord-276364-zyw5aukk cord-027860-s97hdhh6 cord-023017-k6edtg58 cord-271635-tydlyc1q cord-273555-i1d4quos cord-284978-vh1x6pg9 cord-022380-49oti4zg cord-281883-l9yshyc7 cord-265592-r8nlef0h cord-267867-q52nvn0n cord-268467-btfz6ye8 cord-269194-b1wlr3t7 cord-285505-8norumv6 cord-279202-iyteg4h9 cord-263433-oldy0gta cord-284549-edliu3it cord-271091-ffn59sgf cord-281941-97t45w73 cord-256118-gxhhwqdd cord-284693-mgpxnnk0 cord-285868-fz5utxss cord-280878-1kt51viz cord-269294-vx7xr80t cord-265005-e6rpryrh cord-292940-kg1rl6rb cord-286719-1xjmlwqr cord-300642-c7adeis1 cord-291321-ao80xk11 cord-289321-ahl46ql9 cord-266738-8xx1xm2d cord-294842-aesiff1f cord-284551-j0nooxmd cord-299747-qovrstak cord-293653-u2qrxq6t cord-293790-7hyelm88 cord-298033-kzdp9edn cord-293646-d4qcckh1 cord-302295-nblmshni cord-299719-bvdsz626 cord-298736-9bvyp21d cord-303189-ktl4jw8v cord-293857-o8rlqsq5 cord-305303-82n96ukr cord-307556-k2lavvca cord-286334-d9v5xtx7 cord-305039-grsv06j7 cord-305263-fgwf6wy3 cord-284376-plwyjhl8 cord-300154-3p7tjp5j cord-307817-2vy28i4m cord-312080-pu6m4qad cord-305393-96mrxt8a cord-321230-b5a1z14w cord-311823-85wj08gr cord-314753-xflhxb13 cord-305085-bv7udg9k cord-321053-lgae22f8 cord-306934-29ljbl7g cord-325989-nf6ouaq3 cord-324054-d71rj29o cord-317595-siwzjeea cord-318853-mxyxwkhx cord-319754-5isw53wl cord-314148-5xisw9au cord-314254-9ye8tfvz cord-324559-p92y5er2 cord-307934-84zfabti cord-343902-hzh3cjzh cord-340220-raqapqg0 cord-316703-8kxx3034 cord-316968-rowoylge cord-349358-leicos9j cord-323963-whv88ggl cord-334493-rt7gqiev cord-337285-t6qr41wc cord-321505-m40s6uw9 cord-326217-ji0njeha cord-332422-s15o0hie cord-333331-ddcz7zck cord-345898-a6vt8kso cord-332747-u46xryoo cord-335085-7pxkhgbq cord-327135-4c2flue4 cord-341071-nwrl1qws cord-351365-dc9t3vh3 cord-350600-73q8mve4 cord-314567-purplsjn cord-321773-5fw9abzl cord-330110-pamxy4av cord-347992-coby2m6e cord-344084-z4t2wkgk cord-324984-ojrpsdt9 cord-342676-ykog278j cord-347319-lcuma3eh cord-350640-sz6xj5o3 cord-343963-99rd3o79 cord-342901-ca2xxkb2 cord-023354-f2ciho6o cord-007890-bie1veti cord-347710-ff64y6ef cord-023346-8sqbqjm1 cord-350571-6tapkjb6 cord-023364-ut56gczm cord-000083-3p81yr4n cord-009567-osstpum6 cord-010092-uftc8inx cord-010119-t1x9gknd cord-022888-dnsdg04n Creating transaction Updating ent table ===== Reducing parts of speech cord-000174-mgj9zfft cord-003407-f5v3hhr8 cord-000008-3dgjv0x1 cord-000638-ss1435el cord-001421-6t5puo6p cord-001834-6xf4o3oy cord-006061-z9r5htm9 cord-000833-m6abyuvx cord-000786-ofpcgxce cord-000473-jpow6iw1 cord-003158-mhlqnj52 cord-000830-jiy4cp4n cord-005617-bxbogskm cord-006436-61mgtbj4 cord-007236-8hiymqyb cord-007305-pkjfnhro cord-006129-5rog0s98 cord-001848-idmj2d7p cord-003993-3bozjfv7 cord-002410-2zi5iv2t cord-009263-w8bmmgtj cord-002369-shk4n8f6 cord-011182-nbtfb39r cord-258234-qn8xp4v9 cord-013244-d6saaiu9 cord-018220-8m11ig06 cord-017506-t86v3zw3 cord-011026-iapgkz0p cord-026112-58sa5z03 cord-030361-0tepkjdl cord-016343-wc3i54fc cord-010273-0c56x9f5 cord-264713-38dlh3wg cord-261287-l4649du3 cord-253768-y35m3vh1 cord-284904-qw1ig2v4 cord-013176-6ckuya1w cord-018785-tcr5xlf8 cord-255781-55zrmgxq cord-264936-3posyr5n cord-005138-u2lwgyyf cord-265588-1tcaleeo cord-015941-4fz79wzf cord-264326-teahway7 cord-017764-h1w9gbxk cord-256036-gd53s4dv cord-253825-d9borky8 cord-281389-sht0yx4a cord-017948-fqhl1qb4 cord-024003-698d15gk cord-270498-hh6h50t2 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disease; liver; activity; response; cases; analysis; therapy; type; proteins; risk; levels; samples; system; patient; donor; use; viruses; number; studies; antibodies; years; plasma; drug; days; gene; antibody; platelet; control; infections; role; effect verbs: using; showed; include; increases; associated; compared; induced; done; found; performed; based; reports; following; identified; treated; determined; detected; reduced; developed; provided; suggests; infected; required; observed; bound; test; evaluate; indicated; expressed; received; related; leads; inhibits; demonstrated; cause; occurs; involving; result; mediated; containing; obtain; given; decreased; confirms; described; improve; aims; targeting; remaining; collected adjectives: viral; anti; human; clinical; positive; high; specific; different; antiviral; significant; negative; non; immune; chronic; new; low; higher; first; important; several; red; acute; cellular; single; similar; many; molecular; effective; infectious; available; severe; major; lower; common; dependent; potential; possible; present; resistant; total; therapeutic; novel; medical; large; early; respiratory; primary; active; whole; small adverbs: also; however; well; significantly; respectively; therefore; previously; highly; recently; even; still; often; currently; especially; prior; furthermore; ns3; moreover; directly; less; mainly; approximately; now; clinically; usually; together; interestingly; specifically; particularly; later; first; finally; alone; frequently; subsequently; rather; generally; potentially; statistically; fully; least; already; additionally; almost; relatively; indeed; strongly; successfully; commonly; much pronouns: we; it; their; our; its; they; i; them; your; her; he; us; his; she; one; itself; you; themselves; my; mcr-9; me; ns3/4a; himself; him; ourselves; s; p210bcr; mg; isgf3; oneself; herself; esat-6; yourself; r348; pdcs; p24ag; nr-818; mrnas; igg4; λr1; u; smp76; pm.sec-; ns4b; lc16m8; interleukin-15; influenzavirusa; igmcic; ifnar1; he16 proper nouns: HCV; RNA; C; IFN; HIV; T; HBV; PCR; B; RBC; HIV-1; Fig; mg; Hepatitis; CD4; A; China; University; HLA; DNA; CD8; Blood; NS5A; Background; SARS; hepatitis; D; Health; HCC; Hospital; CMV; M; Hb; II; Study; ABO; RHD; L; Design; I; Transfusion; RT; Table; Case; ER; Studies; USA; S.; CD81; Summary keywords: hcv; rna; hiv; virus; cell; hbv; ifn; patient; pcr; dna; hiv-1; result; study; infection; protein; group; sars; ns5a; method; hospital; hla; blood; viral; university; nat; donor; transfusion; platelet; hepatitis; drug; core; cmv; cd8; test; rhd; rbc; liver; health; dat; china; cd81; cd4; antiviral; antibody; anti; abo; treatment; trali; table; system one topic; one dimension: patients file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565067/ titles(s): HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection three topics; one dimension: blood; hcv; virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/, https://www.ncbi.nlm.nih.gov/pubmed/25544499/, https://doi.org/10.1021/jm501371s titles(s): Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 | Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection | Organic Carbamates in Drug Design and Medicinal Chemistry five topics; three dimensions: blood patients transfusion; cells virus hcv; virus infection viral; patients liver cells; patients mg treatment file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/, https://api.elsevier.com/content/article/pii/S0168170215300617, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123043/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159651/, https://www.ncbi.nlm.nih.gov/pubmed/17766124/ titles(s): Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 | Decoding protein networks during virus entry by quantitative proteomics | Viral Infections | Abstracts Oral | 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents Type: cord title: keyword-hcv-cord date: 2021-05-24 time: 23:57 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:hcv ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-256118-gxhhwqdd author: Abadie, R. title: “Caballo”: risk environments, drug sharing and the emergence of a hepatitis C virus epidemic among people who inject drugs in Puerto Rico date: 2020-10-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Sharing drug injection equipment has been associated with the transmission of HCV among PWID through blood contained in the cooker and cotton used to prepare and divide up the drug solution. While epidemiologists often subsume this practice under the sharing of “ancillary equipment,” more attention should be paid to the fact that indirect sharing takes place within the process of joint drug acquisition and preparation. METHODS: We employed an ethnographic approach observing active PWID (N = 33) in four rural towns in Puerto Rico in order to document drug sharing arrangements involved in “caballo”, as this practice is locally known. We explored partners’ motivation to engage in drug sharing, as well as its social organization, social roles and existing norms. FINDINGS: Findings suggest that drug sharing, is one of the main drivers of the HCV epidemic in this population. Lack of financial resources, drug packaging, drug of choice and the desire to avoid the painful effects of heroin withdrawal motivates participants’ decision to partner with somebody else, sharing injection equipment—and risk—in the process. Roles are not fixed, changing not only according to caballo partners, but also, power dynamics. CONCLUSION: In order to curb the HCV epidemic, harm reduction policies should recognize the particular sociocultural contexts in which people inject drugs and make decisions about risk. Avoiding sharing of injection equipment within an arrangement between PWID to acquire and use drugs is more complex than assumed by harm reduction interventions. Moving beyond individual risk behaviors, a risk environment approach suggest that poverty, and a strict drug policy that encourage users to carry small amounts of illicit substances, and a lack of HCV treatment among other factors, contribute to HCV transmission. url: https://doi.org/10.1186/s12954-020-00421-z doi: 10.1186/s12954-020-00421-z id: cord-271635-tydlyc1q author: Abdel-Hamid, Nabil M. title: Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors date: 2018-11-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Hepatocellular carcinoma (HCC) is considered the most frequent tumor that associated with high mortality rate. Several risk factors contribute to the pathogenesis of HCC, such as chronic persistent infection with hepatitis C virus or hepatitis B virus, chronic untreated inflammation of liver with different etiology, oxidative stress and fatty liver disease. Several treatment protocols are used in the treatment of HCC but they also associated with diverse side effects. Many natural products are helpful in the co-treatment and prevention of HCC. Several mechanisms are involved in the action of these herbal products and their bioactive compounds in the prevention and co-treatment of HCC. They can inhibit the liver cancer development and progression in several ways as protecting against liver carcinogens, enhancing effects of chemotherapeutic drugs, inhibiting tumor cell growth and metastasis, and suppression of oxidative stress and chronic inflammation. In this review, we will discuss the utility of diverse natural products in the prevention and co-treatment of HCC, through its capturing of the common risk factors known to lead to HCC and shed the light on their possible mechanisms of action. Our theory assumes that shutting down the risk factor to cancer development pathways is a critical strategy in cancer prevention and management. We recommend the use of these plants side by side to recent chemical medications and after stopping these chemicals, as a maintenance therapy to avoid HCC progression and decrease its global incidence. url: https://api.elsevier.com/content/article/pii/S075333221834280X doi: 10.1016/j.biopha.2018.08.104 id: cord-281883-l9yshyc7 author: Alekseeva, Ekaterina title: Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen date: 2009-06-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression. url: https://www.ncbi.nlm.nih.gov/pubmed/19505299/ doi: 10.1186/1479-0556-7-7 id: cord-347319-lcuma3eh author: Ashfaq, Usman A title: Lysosomotropic agents as HCV entry inhibitors date: 2011-04-12 words: 2579.0 sentences: 146.0 pages: flesch: 50.0 cache: ./cache/cord-347319-lcuma3eh.txt txt: ./txt/cord-347319-lcuma3eh.txt summary: HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. To investigate the antiviral effect of LA (Chloroquine and NH(4)Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. For antiviral screening of Chloroquine and NH(4)Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. We therefore tested the infectivity of HCVpp after treatment of target cells with different concentrations of Chloroquine and NH 4 Cl. HCVpp of 1a and 3a genotype demonstrated dose-dependent inhibition in the presence of Chloroquine and NH 4 Cl. Chloroquine and NH 4 Cl showed greater than 50% reduction of virus infectivity at 50 μM and 10 mM concentration respectively, suggesting a pH-sensitive route of virus entry (Figure 2a and 2b ). abstract: HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH(4)Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH(4)Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH(4)Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH(4)Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH(4)Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV. url: https://doi.org/10.1186/1743-422x-8-163 doi: 10.1186/1743-422x-8-163 id: cord-000473-jpow6iw1 author: Astrovskaya, Irina title: Inferring viral quasispecies spectra from 454 pyrosequencing reads date: 2011-07-28 words: 5363.0 sentences: 296.0 pages: flesch: 54.0 cache: ./cache/cord-000473-jpow6iw1.txt txt: ./txt/cord-000473-jpow6iw1.txt summary: High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences. Results: In this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Results: In this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Given a collection of 454 pyrosequencing reads generated from a viral sample, reconstruct the quasispecies spectrum, i.e., the set of sequences and the relative frequency of each sequence in the sample population. abstract: BACKGROUND: RNA viruses infecting a host usually exist as a set of closely related sequences, referred to as quasispecies. The genomic diversity of viral quasispecies is a subject of great interest, particularly for chronic infections, since it can lead to resistance to existing therapies. High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences. RESULTS: In this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Experimental results show that ViSpA outperforms ShoRAH on simulated error-free reads, correctly assembling 10 out of 10 quasispecies and 29 sequences out of 40 quasispecies. While ShoRAH has a significant advantage over ViSpA on reads simulated with sequencing errors due to its advanced error correction algorithm, ViSpA is better at assembling the simulated reads after they have been corrected by ShoRAH. ViSpA also outperforms ShoRAH on real 454 reads. Indeed, 7 most frequent sequences reconstructed by ViSpA from a real HCV dataset are viable (do not contain internal stop codons), and the most frequent sequence was within 1% of the actual open reading frame obtained by cloning and Sanger sequencing. In contrast, only one of the sequences reconstructed by ShoRAH is viable. On a real HIV dataset, ShoRAH correctly inferred only 2 quasispecies sequences with at most 4 mismatches whereas ViSpA correctly reconstructed 5 quasispecies with at most 2 mismatches, and 2 out of 5 sequences were inferred without any mismatches. ViSpA source code is available at http://alla.cs.gsu.edu/~software/VISPA/vispa.html. CONCLUSIONS: ViSpA enables accurate viral quasispecies spectrum reconstruction from 454 pyrosequencing reads. We are currently exploring extensions applicable to the analysis of high-throughput sequencing data from bacterial metagenomic samples and ecological samples of eukaryote populations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194189/ doi: 10.1186/1471-2105-12-s6-s1 id: cord-319754-5isw53wl author: Balgoma, David title: Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update date: 2020-08-31 words: 12092.0 sentences: 541.0 pages: flesch: 41.0 cache: ./cache/cord-319754-5isw53wl.txt txt: ./txt/cord-319754-5isw53wl.txt summary: Some viruses may use different entry mechanisms, this feature being likely dependent upon the membrane lipid composition of the host cell they infect as well as the particular cell surface factor attachment used. The question regarding whether the lipid-raft domains may serve as platforms to concentrate the proteins required for viral entry and, even though some evidence exists, to activate signaling pathways inside the host cell still remains unsolved. More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . abstract: The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32878290/ doi: 10.3390/metabo10090356 id: cord-263433-oldy0gta author: Barriocanal, Marina title: Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin date: 2015-01-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response. url: https://www.ncbi.nlm.nih.gov/pubmed/25620967/ doi: 10.3389/fimmu.2014.00655 id: cord-332422-s15o0hie author: Belouzard, Sandrine title: Hepatitis C virus entry into the hepatocyte date: 2011-11-07 words: 6987.0 sentences: 365.0 pages: flesch: 47.0 cache: ./cache/cord-332422-s15o0hie.txt txt: ./txt/cord-332422-s15o0hie.txt summary: HCV envelope glycoproteins are key determinants of HCV entry with a role in receptor binding and in mediating the fusion process between the viral envelope and an endosomal host cell membrane. Furthermore, functional non-infectious and capsidless structures, called subviral particles, can be produced when the HCV envelope glycoproteins are expressed alone in lipoprotein producing cell lines [8] , supporting the idea that HCV envelope glycoproteins play an active role during the budding process. The role of SRB1 in HCV entry was first suggested by its ability to mediate soluble E2 binding [13] and it was later confirmed by the inhibition of HCV infection with anti-SRB1 antibodies and by silencing of the protein in hepatoma cells (reviewed in [5, 26, 27] ). Virus-associated lipoproteins are likely playing a role in the early phase of HCV entry, whereas envelope glycoproteins are believed to take the lead after this initial step. abstract: Hepatitis C virus (HCV) is a small enveloped virus with a positive stranded RNA genome belonging to the Flaviviridae family. The virion has the unique ability of forming a complex with lipoproteins, which is known as the lipoviroparticle. Lipoprotein components as well as the envelope proteins, E1 and E2, play a key role in virus entry into the hepatocyte. HCV entry is a complex multistep process involving sequential interactions with several cell surface proteins. The virus relies on glycosaminoglycans and possibly the low-density lipoprotein receptors to attach to cells. Furthermore, four specific entry factors are involved in the following steps which lead to virus internalization and fusion in early endosomes. These molecules are the scavenger receptor SRB1, tetraspanin CD81 and two tight junction proteins, Claudin-1 and Occludin. Although they are essential to HCV entry, the precise role of these molecules is not completely understood. Finally, hepatocytes are highly polarized cells and which likely affects the entry process. Our current knowledge on HCV entry is summarized in this review. url: https://www.ncbi.nlm.nih.gov/pubmed/32215118/ doi: 10.2478/s11535-011-0076-y id: cord-000638-ss1435el author: Beq, Stephanie title: Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date: 2012-04-16 words: 5142.0 sentences: 237.0 pages: flesch: 47.0 cache: ./cache/cord-000638-ss1435el.txt txt: ./txt/cord-000638-ss1435el.txt summary: The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. In contrast, Arizcorreta and colleagues showed that IFNa and ribavirin therapy induces a substantial reduction of circulating sjTRECs, in HIV/HCV co-infected patients, accompanied by sustained naïve CD4 + T-cell defect, suggesting thymic dysfunction [10] . While the number of RTEs was similar in HCV-infected patients at study entry and healthy individuals ( These data demonstrate that, as early as one month following treatment initiation, IFNa induces stronger alterations of naïve Tcell subsets, and more specifically in the RTE compartment than in any other T-cell subset, suggesting a specific effect on thymopoiesis. abstract: Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328332/ doi: 10.1371/journal.pone.0034326 id: cord-255781-55zrmgxq author: Bergman, Scott J. title: Interferons as Therapeutic Agents for Infectious Diseases date: 2011-12-31 words: 6408.0 sentences: 376.0 pages: flesch: 44.0 cache: ./cache/cord-255781-55zrmgxq.txt txt: ./txt/cord-255781-55zrmgxq.txt summary: These agents consist of naturally occurring small proteins with molecular weights of 15,000 to 27,600 Da. 3 Each is considered a first-line option for the treatment of chronic hepatitis C virus (HCV) infection in combination with ribavirin. Along with the list of additional indications approved by the Food and Drug Administration shown in Table 1 , IFN-a was shown to be an effective treatment for the symptoms of an aggressive case of chronic active Epstein-Barr virus, but did not eliminate infection entirely. IFNs have been tested repeatedly against infectious diseases, but injections are used mostly for the treatment of viral hepatitis C and prevention of infections in patients with chronic granulomatous disease clinically. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection abstract: This article explains the rationale for development of interferons as therapeutic agents, and describes commercial products available today. It also provides a summary of studies that have been performed with interferons for use as exogenous biological response modifiers in viral infections. Overall, the best data exist for treatment of viral hepatitis B and C, for which interferons are a cornerstone of therapy. Although infections with human papillomavirus and common cold viruses sometimes respond favorably to interferons, their outcomes are far from ideal. Finally, the role of interferons as vaccine adjuvants is still being explored but could be promising. url: https://www.sciencedirect.com/science/article/pii/S0891552011000560 doi: 10.1016/j.idc.2011.07.008 id: cord-341071-nwrl1qws author: Berzal-Herranz, Alfredo title: Two Examples of RNA Aptamers with Antiviral Activity. Are Aptamers the Wished Antiviral Drugs? date: 2020-07-22 words: 5442.0 sentences: 287.0 pages: flesch: 44.0 cache: ./cache/cord-341071-nwrl1qws.txt txt: ./txt/cord-341071-nwrl1qws.txt summary: Pharmaceuticals 2020, 13 Elucidating the function of each RNA domain and their modus operandi would provide an excellent scenario to address the control of infections caused by RNA viruses, broadening beyond proteins the repertoire of potential target candidates to fight viral diseases. Elucidating the function of each RNA domain and their modus operandi would provide an excellent scenario to address the control of infections caused by RNA viruses, broadening beyond proteins the repertoire of potential target candidates to fight viral diseases. Consequently, in contrast to other nucleic acid based strategies (ribozymes, antisense oligonucleotides, siRNA, among others), aptamers are postulated as excellent candidates to directly interfere with the functioning of essential structural domains of viral RNA genomes. Herein, we present an extension of a video we communicated at the 5th ECMC describing two examples of selection and characterization of aptamers targeting essential structural domains of respective viral RNA genomes, performed in our laboratory [21] . abstract: The current Covid-19 pandemic has pointed out some major deficiencies of the even most advanced societies to fight against viral RNA infections. Once more, it has been demonstrated that there is a lack of efficient drugs to control RNA viruses. Aptamers are efficient ligands of a great variety of molecules including proteins and nucleic acids. Their specificity and mechanism of action make them very promising molecules for interfering with the function encoded in viral RNA genomes. RNA viruses store essential information in conserved structural genomic RNA elements that promote important steps for the consecution of the infective cycle. This work describes two well documented examples of RNA aptamers with antiviral activity against highly conserved structural domains of the HIV-1 and HCV RNA genome, respectively, performed in our laboratory. They are two good examples that illustrate the potential of the aptamers to fill the therapeutic gaps in the fight against RNA viruses. url: https://doi.org/10.3390/ph13080157 doi: 10.3390/ph13080157 id: cord-253825-d9borky8 author: Blaising, Julie title: Arbidol as a broad-spectrum antiviral: An update date: 2014-04-24 words: 8757.0 sentences: 431.0 pages: flesch: 44.0 cache: ./cache/cord-253825-d9borky8.txt txt: ./txt/cord-253825-d9borky8.txt summary: ARB has been shown to display antiviral in vitro and/or in vivo activity against a number of enveloped or non-enveloped RNA or DNA viruses, including influenza viruses A, B and C , respiratory syncytial virus, SARS-CoV, adenovirus, parainfluenza type 5, poliovirus 1, rhinovirus 14, coxsackievirus B5, hantaan virus, Chikungunya virus, HBV and HCV [reviewed in Boriskin et al. Shi and coworkers showed a greater inhibitory effect on influenza A H1N1 when ARB was added before infection or when it was pre-incubated with the virus (Shi et al., 2007) , suggesting that membrane impregnation and/or metabolites could underlie ARB antiviral activity (see Section 6.). Recently, Tannock and coworkers reported a potent antiviral activity of ARB on several virus families responsible of respiratory infections in animals and humans, in particular on influenza A H3N2 (IC50 12 lM), and the non-enveloped Picornaviridae poliovirus 1 and rhinovirus 14 (Brooks et al., 2012 ; see also Brooks et al., 2004) . abstract: Arbidol (ARB) is a Russian-made small indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It also demonstrates inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis B and C, gastroenteritis, hemorrhagic fevers or encephalitis. In this review, we will explore the possibility and pertinence of ARB as a broad-spectrum antiviral, after a careful examination of its physico-chemical properties, pharmacokinetics, toxicity, and molecular mechanisms of action. Recent studies suggest that ARB’s dual interactions with membranes and aromatic amino acids in proteins may be central to its broad-spectrum antiviral activity. This could impact on the virus itself, and/or on cellular functions or critical steps in virus-cell interactions, thereby positioning ARB as both a direct-acting antiviral (DAA) and a host-targeting agent (HTA). In the context of recent studies in animals and humans, we will discuss the prospective clinical use of ARB in various viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/24769245/ doi: 10.1016/j.antiviral.2014.04.006 id: cord-002410-2zi5iv2t author: Bruening, Janina title: The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy date: 2017-02-01 words: 6696.0 sentences: 374.0 pages: flesch: 44.0 cache: ./cache/cord-002410-2zi5iv2t.txt txt: ./txt/cord-002410-2zi5iv2t.txt summary: Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Type III IFNs and ISGs are similarly inducted upon HCV infection of primary human fetal liver cells [98, 99] . In summary, expression of specific IFNL subtypes is induced in PHH and some hepatoma cell lines upon infection with HCV, resulting in limiting virus production. Viral infection and toll-like receptor agonists induce a differential expression of type I and interferons in humans plasmacytoid and monocyte-derived dendritic cells HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons abstract: The human interferon (IFN) response is a key innate immune mechanism to fight virus infection. IFNs are host-encoded secreted proteins, which induce IFN-stimulated genes (ISGs) with antiviral properties. Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response. To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses. As IFNL receptors show a more restricted tissue expression than receptors for other classes of IFNs, IFNL treatment has reduced side effects compared to the classical type I IFN treatment. In HCV therapy, however, IFNL will likely not play an important role as highly effective direct acting antivirals (DAA) exist. Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Finally, we will discuss the lessons learnt from the HCV and IFNL field for virus infections beyond hepatitis C. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309426/ doi: 10.1155/2017/7232361 id: cord-292940-kg1rl6rb author: Butt, Adeel A. title: Rates and Characteristics of SARS‐CoV‐2 Infection in Persons with Hepatitis C Virus Infection date: 2020-10-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Rate of SARS‐CoV‐2 infection and impact of liver fibrosis stage upon infection rates in persons with hepatitis C virus (HCV) infection are unknown. METHODS: We retrospectively analyzed the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well‐established database of HCV infected Veterans in care. We excluded those with missing FIB‐4 score and those with HIV or hepatitis B virus coinfection. We determined the number of persons tested, proportion who tested positive for SARS‐CoV‐2, and the infection rate by age and liver fibrosis stage. RESULTS: Among 172,235 persons with HCV, 14,305 (8.3%) were tested for SARS‐CoV‐2 infection and 892 (6.2%) tested positive. Those with SARS‐CoV‐2 infection were older, more likely to be Black (55.2% vs. 37.8%), obese (body mass index >30kg/m(2) 36.2% vs. 29.7%) and have diabetes or stroke (p<0.0001 for all comparisons). Mean FIB‐4 scores and proportion of persons with cirrhosis (based on a FIB‐4 > 3.25) were similar in both groups. Incidence rate/1,000 tested persons was much higher among Blacks (88.4; 95% CI 81.1,96.2) vs. Whites (37.5; 95% CI 33.1,42.4) but similar among those with cirrhosis (FIB‐4>3.25). The rates were also similar among those who were untreated for HCV vs. those treated with or without attaining a sustained virologic response. CONCLUSIONS: Testing rates among persons with HCV are very low. Persons with infection are more likely to be Black, have a higher body mass index and diabetes or stroke. The degree of liver fibrosis does not appear to have an impact on infection rate. url: https://doi.org/10.1111/liv.14681 doi: 10.1111/liv.14681 id: cord-003993-3bozjfv7 author: Cagliani, Rachele title: Mode and tempo of human hepatitis virus evolution date: 2019-10-25 words: 7845.0 sentences: 400.0 pages: flesch: 40.0 cache: ./cache/cord-003993-3bozjfv7.txt txt: ./txt/cord-003993-3bozjfv7.txt summary: Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses. This finding, as well as the increasing availability of the genome sequences of human-infecting viruses sampled across different geographic areas, has largely expanded our knowledge about the genetic diversity and evolutionary origin of these human pathogens. Studies that did not account for the TDRP provided estimates of the time to the most recent common ancestor (TMRCA) of HCV genotypes in a range between $200 and 1000 years ago [63, 64, 76, 87, 88] ; the origin of the horse virus was dated around 1800 CE [85] . Although several human hepatitis E cases have a zoonotic origin and orthohepeviruses A are found in diverse mammals, recent data indicated that one or more reverse zoonoses led to the emergence and radiation of HEV genotypes [121] . abstract: Human viral hepatitis, a major cause of morbidity and mortality worldwide, is caused by highly diverse viruses with different genetic, ecological, and pathogenetic features. Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses. Thus, with the exclusion of hepatitis D virus, close or distant relatives of these human pathogens were identified in a number of domestic and wild mammals. Also, sequences of human viral strains isolated from different geographic locations and over different time-spans have allowed the application of phylogeographic and molecular dating approaches to large viral phylogenies. In this review, we summarize the most recent insights into our understanding of the evolutionary events and ecological contexts that determined the origin and spread of human hepatitis viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872792/ doi: 10.1016/j.csbj.2019.09.007 id: cord-321773-5fw9abzl author: Cheng, Wenyu title: DDX5 RNA Helicases: Emerging Roles in Viral Infection date: 2018-04-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a prototypical member of the large ATP-dependent RNA helicases family and is known to participate in all aspects of RNA metabolism ranging from transcription to translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-β-catenin signaling, and viral infection have been established. Several RNA viruses have been reported to hijack DDX5 to facilitate various steps of their replication cycles. Furthermore, DDX5 can be bounded by the viral proteins of some viruses with unknown functions. Interestingly, an antiviral function of DDX5 has been reported during hepatitis B virus and myxoma virus infection. Thus, the precise roles of this apparently multifaceted protein remain largely obscure. Here, we provide a rapid and critical overview of the structure and functions of DDX5 with a particular emphasis on its role during virus infection. url: https://www.ncbi.nlm.nih.gov/pubmed/29642538/ doi: 10.3390/ijms19041122 id: cord-267867-q52nvn0n author: Chevalier, Christophe title: Inhibition of Hepatitis C Virus Infection in Cell Culture by Small Interfering RNAs date: 2016-12-14 words: 8001.0 sentences: 395.0 pages: flesch: 48.0 cache: ./cache/cord-267867-q52nvn0n.txt txt: ./txt/cord-267867-q52nvn0n.txt summary: Several siRNAs dramatically reduced or even abrogated the replication of selectable subgenomic HCV replicons upon cotransfection of human hepatoma cells with viral target and siRNAs, or upon transfection of cells supporting autonomous replication of HCV replicon with siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting virus production in cell culture. Several siRNAs dramatically reduced or even abrogated the replication of selectable subgenomic HCV replicons upon cotransfection of human hepatoma cells with viral target and siRNAs, or upon transfection of cells supporting autonomous replication of HCV replicon with siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting virus production in cell culture. We sought to determine whether the siRNAs si240-1a, si244, and si313, shown to be the most efficient in inhibiting the replication of HCV subgenomic replicons both transiently and under selective pressure, are also capable of efficiently blocking virus infection in cell culture. abstract: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and hepatocellular carcinoma, yet fully efficacious treatments are missing. In this study, we investigated RNA interference (RNAi), a specific gene silencing process mediated by small interfering RNA (siRNA) duplexes, as an antiviral strategy against HCV. Synthetic siRNAs were designed to target conserved sequences of the HCV 5′ nontranslated region (NTR) located in a functional, stem–loop structured domain of the HCV internal ribosome entry site (IRES), which is crucial for initiation of polyprotein translation. Several siRNAs dramatically reduced or even abrogated the replication of selectable subgenomic HCV replicons upon cotransfection of human hepatoma cells with viral target and siRNAs, or upon transfection of cells supporting autonomous replication of HCV replicon with siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting virus production in cell culture. One siRNA, targeting a sequence that is highly conserved across all genotypes and forms a critical pseudoknot structure involved in translation, was identified as the most promising therapeutic candidate. These results indicate that the HCV life cycle can be efficiently blocked by using properly-designed siRNAs that target functionally important, highly conserved sequences of the HCV IRES. This finding offers a novel approach towards developing IRES-based antiviral treatment for chronic HCV infections. url: https://www.sciencedirect.com/science/article/pii/S152500161632439X doi: 10.1038/sj.mt.6300186 id: cord-327135-4c2flue4 author: Chinnaswamy, S title: Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections date: 2016-06-09 words: 9813.0 sentences: 499.0 pages: flesch: 48.0 cache: ./cache/cord-327135-4c2flue4.txt txt: ./txt/cord-327135-4c2flue4.txt summary: Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. Three independent groups conducted genome-wide association studies (GWASs) involving treatment response to chronic hepatitis C virus (HCV) infections, in three different geographical regions of the world, and reported that single-nucleotide polymorphisms (SNPs) in the IFNL locus (Figure 1 ), had strong association with treatment-induced HCV clearance irrespective of ethnicity and geographical location of the hosts. 49 In stark contrast, a dominant model of inheritance (of the non-beneficial IFNL SNP minor allele) has consistently given the best explanation on the observed phenotypes in association studies with both spontaneous clearance and IFN-based treatment response in chronic HCV infections. abstract: Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-λ4 as the prime ‘functional’ variant, the relevance of other polymorphisms regulating the expression of IFN-λ3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-λ biology. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/gene.2016.24) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1038/gene.2016.24 doi: 10.1038/gene.2016.24 id: cord-000786-ofpcgxce author: Chua, Brendon Y. title: Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses date: 2012-10-16 words: 6398.0 sentences: 293.0 pages: flesch: 47.0 cache: ./cache/cord-000786-ofpcgxce.txt txt: ./txt/cord-000786-ofpcgxce.txt summary: Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. Virus-like particles (VLPs) possess features which make them ideal vehicles for the delivery of viral antigens to the immune system; (i) antibody epitopes are presented in the native conformation for induction of potentially neutralising antibodies (ii) multiple T cell, CD4 + and CD8 + , epitopes are packaged in VLPs (iii) VLPs lack regulatory proteins as well as genetic material that could pose a risk of reversion or mutation (iv) encouraging results have been obtained using insect cell-derived recombinant VLPs expressing HCV antigens which induce virus-specific humoral and cellular responses [16] [17] [18] (v) HCV VLPs appear to possess properties favourable for dendritic cell uptake [19] and (vi) they exhibit superior immunogenicity and antigenicity over recombinant protein and DNA-based vaccine approaches [16, 17] . abstract: Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam(2)Cys (E(8)Pam(2)Cys) to enhance the immunogenicity of VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a. While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an aluminium hydroxide-based adjuvant (Alum). Dramatically improved VLP and E2-specific antibody responses were observed in VLP+E(8)Pam(2)Cys vaccinated mice where up to 3 doses of non-adjuvanted or traditionally alum-adjuvanted VLPs was required to match the antibody titres obtained with a single dose of VLPs formulated with this lipopeptide. This result also correlated with significantly higher numbers of specific antibody secreting cells that was detected in the spleens of VLP+E(8)Pam(2)Cys vaccinated mice and greater ability of sera from these mice to neutralise the binding and uptake of VLPs by Huh7 cells. Moreover, vaccination of HLA-A2 transgenic mice with this formulation also induced better VLP-specific IFN-γ-mediated responses compared to non-adjuvanted VLPs but comparable levels to that achieved when coadministered with complete freund’s adjuvant. These results suggest overall that the immunogenicity of HCV VLPs can be significantly improved by the addition of this novel adjuvant by targeting their delivery to DCs and could therefore constitute a viable vaccine strategy for the treatment of HCV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472981/ doi: 10.1371/journal.pone.0047492 id: cord-000830-jiy4cp4n author: Cobo, Fernando title: Application of Molecular Diagnostic Techniques for Viral Testing date: 2012-11-30 words: 7969.0 sentences: 385.0 pages: flesch: 39.0 cache: ./cache/cord-000830-jiy4cp4n.txt txt: ./txt/cord-000830-jiy4cp4n.txt summary: The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. The use of amplification techniques such as polymerase chain reaction (PCR), real-time PCR or nucleic acid sequence-based amplification (NASBA) [3] for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range [4, 5] . NASBA assays could identify active infection by detecting viral messenger RNA (mRNA) but the most widely used tests in clinical virus diagnosis are quantitative real-time PCR techniques [8] . Some real-time PCR assays such as LightCycler parvovirus B19 quantitative assay (Roche Diagnostics, Indianapolis, IN) and ABI TaqMan (Applied Biosystems) have been developed for detecting B19 nucleic acids in association with infection during pregnancy or assessing the prevalence of the virus DNA in blood products [62, 63] . abstract: Nucleic acid amplification techniques are commonly used currently to diagnose viral diseases and manage patients with this kind of illnesses. These techniques have had a rapid but unconventional route of development during the last 30 years, with the discovery and introduction of several assays in clinical diagnosis. The increase in the number of commercially available methods has facilitated the use of this technology in the majority of laboratories worldwide. This technology has reduced the use of some other techniques such as viral culture based methods and serological assays in the clinical virology laboratory. Moreover, nucleic acid amplification techniques are now the methods of reference and also the most useful assays for the diagnosis in several diseases. The introduction of these techniques and their automation provides new opportunities for the clinical laboratory to affect patient care. The main objectives in performing nucleic acid tests in this field are to provide timely results useful for high-quality patient care at a reasonable cost, because rapid results are associated with improvements in patients care. The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. This review is an up-to-date of the main nucleic acid techniques and their clinical applications, and special challenges and opportunities that these techniques currently provide for the clinical virology laboratory. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522074/ doi: 10.2174/1874357901206010104 id: cord-303189-ktl4jw8v author: Coccia, Eliana M. title: Early IFN type I response: Learning from microbial evasion strategies date: 2015-03-31 words: 15202.0 sentences: 738.0 pages: flesch: 40.0 cache: ./cache/cord-303189-ktl4jw8v.txt txt: ./txt/cord-303189-ktl4jw8v.txt summary: Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. In these cells, the HCV-induced miR-21 has been recently reported to be involved in evasion of IFN-I production and stimulation of HCV replication, upon suppression of MyD88 and IRAK1 expression, that is required for the TLR7-mediated sensing of the virus [100] . Amongst RNA viruses that, as HCV, can establish a persistent infection, HIV-1, a lentivirus from the Retroviridae family, represents a paradigm for its ability to prevent or circumvent the innate immune response mediated by IFN-I. Overall, viruses as HCV and HIV-1 have evolved nifty strategies to dampen the host innate response in cells where a productive infection may take place, while they induce infection-independent mechanisms in non-permissive cells to facilitate the viral life cycle and promote a chronic inflammation. abstract: Abstract Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens. Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. On the other hand an inverse interference to escape the IFN system is largely exploited by pathogens through a number of tactics and tricks aimed at evading, inhibiting or manipulating the IFN pathway, that result in progression of infection or establishment of chronic disease. In this review we discuss the interplay between the IFN system and some selected clinically important and challenging viruses and bacteria, highlighting the wide array of pathogen-triggered molecular mechanisms involved in evasion strategies. url: https://doi.org/10.1016/j.smim.2015.03.005 doi: 10.1016/j.smim.2015.03.005 id: cord-009263-w8bmmgtj author: Colpitts, Che C. title: Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process date: 2020-03-18 words: 7111.0 sentences: 385.0 pages: flesch: 41.0 cache: ./cache/cord-009263-w8bmmgtj.txt txt: ./txt/cord-009263-w8bmmgtj.txt summary: The initial binding step primarily involving the lipoprotein component of LVPs likely is a rather unspecific event, which results in the concentration of the virus at the basolateral membrane of hepatocytes and exposure of viral envelope glycoprotein domains that enable the virus to specifically interact with SR-BI, CD81, and CLDN1 (post-binding). Initial attachment of LVPs to hepatocyte basolateral membranes likely involves virus-associated lipoprotein components (particularly apoE [9,13,30-35]), and virus envelope glycoproteins, which interact with highly sulfated heparan sulfate proteoglycans (HSPG) [36] [37] [38] (particularly syndecans [39] [40] [41] ), LDL receptor (LDLR) [42] [43] [44] [45] and SR-BI [46] [47] [48] [49] [50] [51] on the cell surface ( Figure 1 ). Initial attachment of LVPs to hepatocyte basolateral membranes likely involves virus-associated lipoprotein components (particularly apoE [9,13,30-35]), and virus envelope glycoproteins, which interact with highly sulfated heparan sulfate proteoglycans (HSPG) [36] [37] [38] (particularly syndecans [39] [40] [41] ), LDL receptor (LDLR) [42] [43] [44] [45] and SR-BI [46] [47] [48] [49] [50] [51] on the cell surface ( Figure 1 ). abstract: Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver disease worldwide. Its tissue and species tropism are largely defined by the viral entry process that is required for subsequent productive viral infection and establishment of chronic infection. This review provides an overview of the viral and host factors involved in HCV entry into hepatocytes, summarizes our understanding of the molecular mechanisms governing this process and highlights the therapeutic potential of host-targeting entry inhibitors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140000/ doi: 10.3390/ijms21062091 id: cord-005617-bxbogskm author: Conway, Anna title: Hepatitis C Screening in Community-Based Voluntary Counselling and Testing Services in Europe: An Observational Study from the COBATEST Network 2014–2018 date: 2019-11-20 words: 3240.0 sentences: 146.0 pages: flesch: 51.0 cache: ./cache/cord-005617-bxbogskm.txt txt: ./txt/cord-005617-bxbogskm.txt summary: This study aims to describe the population being screened for anti-HCV antibodies in the COBATEST Network and identify risk factors associated with a reactive HCV screening test result in the period 2014–2018. This study describes HCV screening activity in CBVCT services, describes the populations being screened, describes the proportion of reactive HCV screening tests and identifies risk factors associated with a reactive HCV screening test result in the COBATEST Network in the years 2014-2018. Secondly, the clients screened for HCV and clients with a reactive screening test were described by socio-demographic characteristics (gender [men, women, transgender], age group [16-24, 25-44, 45-64, > 65], migrants [defined as been born in a country different to the country where the CBVCT service is placed], region of origin), key populations (MSM, PWID, SW) and epidemiological variables (HIV status, HCV screening test results and RNA test results). abstract: The COBATEST Network links community-based voluntary counselling and testing (CBVCT) services in the European region and collects testing data using standardised data collection tools. This study aims to describe the population being screened for anti-HCV antibodies in the COBATEST Network and identify risk factors associated with a reactive HCV screening test result in the period 2014–2018. Clients aged > 16 screened for HCV in the period 2014–2018 at one of the Network’s CBVCT services were included in the study. In the 5 year period, 7426 clients were screened for HCV in 22 centres in 10 countries and anti-HCV antibodies were detected in 113 (1.5%). The majority of people screened were aged 25–44, men who have sex with men (MSM), not HIV+ , not reporting a history of injecting drug use or sex work. Detection of anti-HCV antibodies was associated with being HIV + MSM (aOR 9.1, 95% CI 3.8; 21.8 compared to HIV-clients) and being a person who injects drugs (PWID, aOR 28.1, 95% CI 17.6; 45.0, compared to people with no history of injecting drug use). This study demonstrates that HIV-MSM with no history of injection drug use are using CBVCT services for HCV screening, but reactive screening test is associated with being HIV+ or PWID. The integration of HCV screening into the CBVCT service model may widen access to testing for populations that may otherwise not be tested. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10900-019-00780-0) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095007/ doi: 10.1007/s10900-019-00780-0 id: cord-011182-nbtfb39r author: Dehghani, Behzad title: Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran date: 2019-04-20 words: 6186.0 sentences: 387.0 pages: flesch: 55.0 cache: ./cache/cord-011182-nbtfb39r.txt txt: ./txt/cord-011182-nbtfb39r.txt summary: Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. In this study, we employed several bioinformatics tools to find important mutations in domain 1 of the core protein, general properties of B-cell and T-cell epitopes, modification sites, and structure of domain 1 in Iranian HCV infected samples from 2006 to 2017. (2002 compared sequences of the core protein of Subtype 1b HCV strains obtained from patients with and without HCC and found some amino acid mutation sites (Ogata et al. Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy abstract: Hepatitis C virus (HCV) infection is a serious global health problem and a cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Bioinformatics software has been an effective tool to study the HCV genome as well as core domains. Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. Domain 1 sequences of 188 HCV samples isolated from 2006 to 2017, Iran, were retrieved from NCBI gene bank. Using several tools, all sequences were analyzed for determination of mutations, physicochemical analysis, B-cell epitopes prediction, T-cell and CTL epitopes prediction, post modification, secondary and tertiary structure prediction. Our analysis determined several mutations in some special positions (70, 90, 91, and 110) that are associated with HCC and hepatocarcinogenesis, efficacy of triple therapy and sustained virological response, and interaction between core and CCR6. Several B-cell, T-cell, and CTL epitopes were recognized. Secondary and tertiary structures were mapped fordomain1 and core proteins. Our study, as a first report, offered inclusive data about frequent mutation in HCV-core gene domain 1 in Iranian sequences that can provide helpful analysis on structure and function of domain 1 of the core gene. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223762/ doi: 10.1007/s10989-019-09838-y id: cord-026112-58sa5z03 author: Dehghani-Dehej, Farzaneh title: Prevalence of HCV and/or HBV coinfection in Iranian HIV-infected patients date: 2020-04-24 words: 4005.0 sentences: 198.0 pages: flesch: 47.0 cache: ./cache/cord-026112-58sa5z03.txt txt: ./txt/cord-026112-58sa5z03.txt summary: This study aimed to investigate molecular epidemiology of HBV and HCV coinfection in Iranian HIV-infected individuals. Materials & methods: In this cross-sectional study, serological markers of HBV and HCV infection (hepatitis B surface antigen [HBsAg], hepatitis B e-antigen [HBeAg], hepatitis B e-antibody [HBeAb] and hepatitis B core antibody [HBcAb]) and anti-HCV antibodies [anti-HCV Abs] were tested in 198 Iranian HIV-infected patients. HIV/HBV-coinfected people have a higher rate of progression to liver fibrosis, cirrhosis, HCC, less clearance of HBsAg and occult HBV infections (OBI) are more frequent in these patients [13] . The aim for this study is to investigate the prevalence of HCV and/or HBV coinfection in Iranian HIV-infected individuals. According to a previous study, prevalence of cirrhosis in HIV/HBV/HCV triple-infected patients was higher than HIV/HBV-or HIV/HCV-coinfected individuals [57] . abstract: Aim: HIV-infected patients risk coinfection with HBV and HCV. This study aimed to investigate molecular epidemiology of HBV and HCV coinfection in Iranian HIV-infected individuals. Materials & methods: In this cross-sectional study, serological markers of HBV and HCV infection (hepatitis B surface antigen [HBsAg], hepatitis B e-antigen [HBeAg], hepatitis B e-antibody [HBeAb] and hepatitis B core antibody [HBcAb]) and anti-HCV antibodies [anti-HCV Abs] were tested in 198 Iranian HIV-infected patients. From plasma, HBV viral load was determined using COBAS TaqMan 48, and HCV-RNA was detected by reverse transcriptase-nested PCR. Results: 85 out of 198 (42.9%) patients were anti-HCV Ab positive and 42/198 (21.2%) had detectable HCV-RNA. Eight (4.0%) had traceable HBV-DNA. All these patients were infected by HBV genotype D. 55 (27.8%) were HBcAb positive. Nine (4.4%) were HBsAg and anti-HCV Ab positive. Conclusion: None were HIV-RNA/HCV-RNA/HBV-DNA positive, 21.2% were HIV-RNA/HCV-RNA positive and 4.0% were HIV-RNA/HBV-DNA positive. Therefore, studies on diagnosing these infections in HIV-infected individuals may be valuable. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273902/ doi: 10.2217/fvl-2019-0066 id: cord-335085-7pxkhgbq author: Dessau, R. B. title: Coronaviruses in spinal fluid of patients with acute monosymptomatic optic neuritis date: 2009-01-29 words: 2145.0 sentences: 130.0 pages: flesch: 64.0 cache: ./cache/cord-335085-7pxkhgbq.txt txt: ./txt/cord-335085-7pxkhgbq.txt summary: Material and methods ‐ Spinal fluids from 37 patients with AMON and 15 surgical control patients with protrusion of the intervertebral disk were assayed with a nested multiplex polymerase chain reaction with primers specific for human coronaviruses strain (HCV) 229E and OC43. To investigate the possibility of an infection with human coronaviruses (HCV) in early MS and as a possible cause of AMON we have analyzed cerebrospinal fluid (CSF) from patients with AMON using reverse transcriptase reaction and the polymerase chain reaction (RT-PCR) applying primers specific for HCV. CSF from 4 patients and 1 control ( Table 2) were positive on nested RT-PCR using the HCV-229E primers and all samples were negative with the HCV-OC43 primers. HCV-229E RNA was found in the CSF by RT-PCR in 4 of 37 patients with AMON and in 1 of 15 controls. abstract: Acute monosymptomatic optic neuritis (AMON) may be an initial symptom of multiple sclerosis (MS). Coronaviruses have been implicated in the etiology of MS. The objective of the present study was to look for coronaviral RNA in AMON, which could be present in the initial stages of the development of MS. Material and methods ‐ Spinal fluids from 37 patients with AMON and 15 surgical control patients with protrusion of the intervertebral disk were assayed with a nested multiplex polymerase chain reaction with primers specific for human coronaviruses strain (HCV) 229E and OC43. Results ‐ Four patients and 1 control were positive for HCV‐229E. No evidence of HCV‐OC43 was found. The frequency of positive samples was low and there was no statistical difference between AMON and controls. Conclusion ‐ This study does not provide evidence for an etiological role of human coronaviruses in acute monosymptomatic optic neuritis. url: https://www.ncbi.nlm.nih.gov/pubmed/10442448/ doi: 10.1111/j.1600-0404.1999.tb01043.x id: cord-299747-qovrstak author: Deval, Jerome title: Inhibition of viral RNA polymerases by nucleoside and nucleotide analogs: therapeutic applications against positive-strand RNA viruses beyond hepatitis C virus date: 2014-09-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A number of important human infections are caused by positive-strand RNA viruses, yet almost none can be treated with small molecule antiviral therapeutics. One exception is the chronic infection caused by hepatitis C virus (HCV), against which new generations of potent inhibitors are being developed. One of the main molecular targets for anti-HCV drugs is the viral RNA-dependent RNA polymerase, NS5B. This review summarizes the search for nucleoside and nucleotide analogs that inhibit HCV NS5B, which led to the FDA approval of sofosbuvir in 2013. Advances in anti-HCV therapeutics have also stimulated efforts to develop nucleoside analogs against other positive-strand RNA viruses. Although it remains to be validated in the clinic, the prospect of using nucleoside analogs to treat acute infections caused by RNA viruses represents an important paradigm shift and a new frontier for future antiviral therapies. url: https://api.elsevier.com/content/article/pii/S1879625714001692 doi: 10.1016/j.coviro.2014.08.004 id: cord-298033-kzdp9edn author: Domingo, Esteban title: Quasispecies dynamics in disease prevention and control date: 2019-11-08 words: 16346.0 sentences: 735.0 pages: flesch: 37.0 cache: ./cache/cord-298033-kzdp9edn.txt txt: ./txt/cord-298033-kzdp9edn.txt summary: Quasispecies dynamics in disease prevention and control following statement will be obvious to the reader: "If a single mutation is able to confer resistance to an antiviral agent, and the mutation does not cause a significant selective disadvantage to the virus (fitness decrease) in the considered environment, a drug-resistant virus mutant will be present in most, if not all, virus populations" (Domingo, 1989) . The phenotypic barrier to drug resistance is equivalent to the fitness cost inflicted upon the virus by the mutations and corresponding amino acid substitution(s) required for resistance [Fitness cost is treated in Chapter 4 (Section 4.6) and in Chapter 7 (Section 7.4.2) in connection with the frequency of monoclonal antibody-or cytotoxic T-cell-escape mutants in viral populations]. For viruses that replicate in cell culture, it is possible to estimate the minimal viral population size needed to select a drug-resistant mutant which is generally positively correlated with the genetic barrier ( Fig. 8.5 ). abstract: Medical interventions to prevent and treat viral disease constitute evolutionary forces that may modify the genetic composition of viral populations that replicate in an infected host and influence the genomic composition of those viruses that are transmitted and progress at the epidemiological level. Given the adaptive potential of viruses in general and the RNA viruses in particular, the selection of viral mutants that display some degree of resistance to inhibitors or vaccines is a tangible challenge. Mutant selection may jeopardize control of the viral disease. Strategies intended to minimize vaccination and treatment failures are proposed and justified based on fundamental features of viral dynamics explained in the preceding chapters. The recommended use of complex, multiepitopic vaccines, and combination therapies as early as possible after initiation of infection falls under the general concept that complexity cannot be combated with simplicity. It also follows that sociopolitical action to interrupt virus replication and spread as soon as possible is as important as scientifically sound treatment designs to control viral disease on a global scale. url: https://www.sciencedirect.com/science/article/pii/B9780128163313000088 doi: 10.1016/b978-0-12-816331-3.00008-8 id: cord-286719-1xjmlwqr author: Draz, Mohamed Shehata title: Applications of gold nanoparticles in virus detection date: 2018-02-15 words: 18990.0 sentences: 901.0 pages: flesch: 37.0 cache: ./cache/cord-286719-1xjmlwqr.txt txt: ./txt/cord-286719-1xjmlwqr.txt summary: The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. These techniques represent the majority of molecular techniques applied in virus detection and include various types of target amplification techniques (e.g., PCR, loop-mediated isothermal amplification (LAMP), transcription-mediated amplification, and nucleic acid sequence-based amplification), signal amplification techniques (e.g., branched DNA and hybrid capture), and probe amplification techniques (e.g., ligase chain reaction and strand-displacement amplification). [70] developed an impedimetric electrochemical assay for the detection of AIV M gene sequences based on measuring changes in the impedimetric behavior of the electrode when the target DNA hybridizes with the capture DNA probes immobilized onto its surface and is subsequently labeled by AuNPs via streptavidin/ biotin interaction (Fig. 12C) . abstract: Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications. url: https://doi.org/10.7150/thno.23856 doi: 10.7150/thno.23856 id: cord-018220-8m11ig06 author: Duncan, Coley B. title: Viral Infections date: 2009-02-02 words: 6477.0 sentences: 324.0 pages: flesch: 45.0 cache: ./cache/cord-018220-8m11ig06.txt txt: ./txt/cord-018220-8m11ig06.txt summary: The recommendations of the Advisory Committee on Immunization Practices (ACIP) 2007 relating to the elderly, include vaccination of all persons ³ 50 years, vaccination of residents of nursing homes and chronic-care facilities, vaccination of healthcare personnel, and vaccination of healthy household contacts (including children) and caregivers of adults ³ 50 years (3) . In a prospective study from Rochester, NY, using a combination of viral culture, RT-PCR and serology for diagnosis, RSV infection was documented in 3-7% of 608 healthy elderly and 4-10% of adults with chronic cardiopulmonary conditions over four winter seasons (16) . In healthy elderly patients and in adults with chronic pulmonary disease, low serum neutralizing antibody titers are associated with increased risk of hospitalization with RSV infection suggesting a vaccine may be beneficial. Although PIV infections are not commonly documented in older adults, several studies of community-acquired pneumonia and chronic obstructive pulmonary disease (COPD) exacerbations implicate PIV as a cause in 2-17% of cases (25, 26) . abstract: Although influenza remains indisputably the most significant viral pathogen in adults, other viruses such as respiratory syncytial virus, parainfluenza viruses, and human metapneumovirus are now recognized as significant pathogens in older populations. Oseltamivir and zanamivir are antiviral agents that are effective for the treatment and prophylaxis of influenza A and B. For treatment and for optimal effect, therapy should be initiated within 48 h of symptom onset. Infection with hepatitis viruses may be more severe in older adults with more fulminate disease as observed with acute hepatitis A and a more rapid progression to cirrhosis with hepatitis C. Outbreaks of viral gastroenteritis are common in long-term care facilities, and infection may lead to death due to dehydration and oliguria. The incidence of herpes zoster increases with advancing age and carries with it a significant risk of post herpetic neuralgia. The use of antiviral medications and corticosteroids may reduce the incidence and severity of chronic pain. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123043/ doi: 10.1007/978-1-60327-534-7_23 id: cord-013244-d6saaiu9 author: Eijsink, Job F. H. title: Cost-effectiveness of hepatitis C virus screening, and subsequent monitoring or treatment among pregnant women in the Netherlands date: 2020-10-16 words: 5915.0 sentences: 310.0 pages: flesch: 51.0 cache: ./cache/cord-013244-d6saaiu9.txt txt: ./txt/cord-013244-d6saaiu9.txt summary: However, it is conceivable that in the near future DAA treatment of HCV-infected women during pregnancy becomes available, not only to limit disease progression in the patient, but also to prevent vertical transmission of the virus to the child. A screening model linked to HCV-disease states within a Markov model was used to evaluate the cost-effectiveness (CE) of HCV screening of pregnant women, with initial treatment during pregnancy, compared to current practice (no screening and no intervention) from a health-care payer perspective in the Netherlands. We subsequently determined the cost-effectiveness and budget impact of HCV screening and treatment among the four cohorts of pregnant women following the different scenarios and comparisons. Our present study demonstrates that HCV screening of pregnant women and subsequent immediate treatment of all HCV-positive individuals with DAAs is a cost-effective intervention in the Netherlands. abstract: BACKGROUND: The prevalence of diagnosed chronic hepatitis C virus (HCV) infection among pregnant women in the Netherlands is 0.26%, yet many cases remain undiagnosed. HCV screening and treatment of pregnant HCV carriers could reduce the burden of disease and limit vertical transmission from mother to child. We assessed the impact of HCV screening and subsequent treatment with new direct-acting antivirals (DAAs) among pregnant women in the Netherlands. METHODS: An HCV natural history Markov transition state model was developed, to evaluate the public-health and economic impact of HCV screening and treatment. Besides all 179,000 pregnant women in the Netherlands (cohort 1), we modelled 3 further cohorts: all 79,000 first-time pregnant women (cohort 2), 33,000 pregnant migrant women (cohort 3) and 16,000 first-time pregnant migrant women (cohort 4). Each cohort was analyzed in various scenarios: i no intervention, i.e., the current practice, ii screen-and-treat, i.e., the most extensive approach involving treatment of all individuals found HCV-positive, and iii screen-and-treat/monitor, i.e., a strategy involving treatment of symptomatic (F1–F4) patients and follow-up of asymptomatic (F0) HCV carriers with subsequent treatment only at progression. RESULTS: For all cohorts, comparison between scenarios (ii) and (i) resulted in ICERs between €9,306 and €10,173 per QALY gained and 5 year budget impacts varying between €6,283,830 and €19,220,405. For all cohorts, comparison between scenarios (iii) and (i) resulted in ICERs between €1,739 and €2,749 per QALY gained and budget impacts varying between €1,468,670 and €5,607,556. For all cohorts, the ICERs (scenario iii versus ii) involved in delayed treatment of asymptomatic (F0) HCV carriers varied between €56,607 and €56,892, well above the willingness-to-pay (WTP) threshold of €20,000 per QALY gained and even above a threshold of €50,000 per QALY gained. CONCLUSION: Universal screening for HCV among all pregnant women in the Netherlands is cost-effective. However, it would be reasonable to consider smaller risk groups in view of the budget impact of the intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10198-020-01236-2) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561704/ doi: 10.1007/s10198-020-01236-2 id: cord-011026-iapgkz0p author: El-Bitar, Alaa M. H. title: Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus date: 2019-07-06 words: 5247.0 sentences: 296.0 pages: flesch: 53.0 cache: ./cache/cord-011026-iapgkz0p.txt txt: ./txt/cord-011026-iapgkz0p.txt summary: title: Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). For dengue virus infectivity, serially diluted venom fractions and Smp76 were mixed with fixed amount of DENV and incubated for 2 h at 37 °C. The above results suggest that the Smp76 directly affects HCV particles and/or host cells in the culture medium to inhibit the viral infection and does not have an antiviral effect in the cells. To determine whether the antiviral activity of Smp76 peptide (previously described) was specific to HCV and DENV, a Schematic of infection assay. The exact mechanism by which Smp76 exerts its antiviral activity against HCV and DENV to inhibit infecting their target cells need further studies. abstract: Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC(50) of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223391/ doi: 10.1007/s10989-019-09888-2 id: cord-264326-teahway7 author: Eleftheriou, Phaedra title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus date: 2020-05-29 words: 5403.0 sentences: 256.0 pages: flesch: 50.0 cache: ./cache/cord-264326-teahway7.txt txt: ./txt/cord-264326-teahway7.txt summary: According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since the 3D structure of the active site of the enzyme is crucial for catalytic activity, we proceeded to a comparison of the SARS-CoV-2 main protease, Mpro, with the HIV-1 protease, the HCV protease (NS3 protein) and the human proteases DPP-4, thrombin, Factor Xa, renin and ACE, which constitute known drug targets with approved inhibitors. The structural similarity between the SARS-CoV-2 protease and some of the selected proteases, in combination with the existence of the same amino acids at certain positions of the substrate cleavage site, such as Ser at the P1'' position of the recognition sequence of the HCV protease and thrombin are promising features in the effort to identify effective SARS-CoV-2 protease inhibitors among the approved drugs of the selected proteases. abstract: The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and α-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia. url: https://www.ncbi.nlm.nih.gov/pubmed/32485894/ doi: 10.3390/molecules25112529 id: cord-344084-z4t2wkgk author: Ellwanger, Joel Henrique title: Beyond HIV infection: neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases date: 2020-05-30 words: 15735.0 sentences: 840.0 pages: flesch: 45.0 cache: ./cache/cord-344084-z4t2wkgk.txt txt: ./txt/cord-344084-z4t2wkgk.txt summary: The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. In agreement with studies showing that CCR5Δ32 homozygous genotype is a risk factor for symptomatic WNV infection in humans, Ccr5-/-WNV-infected mice showed a reduced capacity of viral control, increased disease severity, impaired leukocyte trafficking towards the brain, and high mortality rates than Ccr5 wild-type mice. In conclusion, although tissue analysis and evidence obtained in vitro suggest that the CCR5 is potentially involved in the pathogenesis of HPV, most studies point to a lack of involvement of CCR5Δ32 in susceptibility to HPV infection or HPV-associated diseases. abstract: The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human C-C chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in “CCR5 research” are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed. url: https://api.elsevier.com/content/article/pii/S0168170220302938 doi: 10.1016/j.virusres.2020.198040 id: cord-269194-b1wlr3t7 author: Engstrom-Melnyk, Julia title: Chapter 5 Clinical Applications of Quantitative Real-Time PCR in Virology date: 2015-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Since the invention of the polymerase chain reaction (PCR) and discovery of Taq polymerase, PCR has become a staple in both research and clinical molecular laboratories. As clinical and diagnostic needs have evolved over the last few decades, demanding greater levels of sensitivity and accuracy, so too has PCR performance. Through optimisation, the present-day uses of real-time PCR and quantitative real-time PCR are enumerable. The technique, combined with adoption of automated processes and reduced sample volume requirements, makes it an ideal method in a broad range of clinical applications, especially in virology. Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. All of these serve vital roles in the continuum of care to enhance patient management. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats. url: https://api.elsevier.com/content/article/pii/S0580951715000069 doi: 10.1016/bs.mim.2015.04.005 id: cord-325989-nf6ouaq3 author: Es-Saad, Salwa title: Regulators of innate immunity as novel targets for panviral therapeutics date: 2012-09-24 words: 3731.0 sentences: 201.0 pages: flesch: 34.0 cache: ./cache/cord-325989-nf6ouaq3.txt txt: ./txt/cord-325989-nf6ouaq3.txt summary: The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. In the near future, targeting specific regulators of PRR-mediated innate response to withdraw viral subversion mechanisms, and access to novel surrogate measurable effector markers, hold the promise of new panviral therapeutics that will minimize adverse effects associated with type I IFN therapy. abstract: Interferons (IFNs) have long been used as an immunomodulatory therapy for a large array of acute and chronic viral infections. However, IFN therapies have been plagued by severe side effects. The discovery of pathogen recognition receptors (PRR) rejuvenated the interest for immunomodulatory therapies. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. url: https://www.sciencedirect.com/science/article/pii/S1879625712001356 doi: 10.1016/j.coviro.2012.08.009 id: cord-002369-shk4n8f6 author: Fahmy, Ahmed M. title: The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date: 2017-01-09 words: 6131.0 sentences: 355.0 pages: flesch: 50.0 cache: ./cache/cord-002369-shk4n8f6.txt txt: ./txt/cord-002369-shk4n8f6.txt summary: The expression of HCV proteins results in the induction of a major rearrangement of host cell membranes, thus leading to the formation of a complex membranous compartment termed the membranous web (MW), which favors viral RNA replication and assembly 3, 4 . To determine whether LC3 or the ATG5-12 conjugate modulates HCV RNA replication, we analyzed the effects of silencing these autophagy genes on viral RNA replication in Huh7 cells stably expressing the JFH1 subgenomic replicon (SGR). Because silencing of LC3 expression led to a clear inhibition of HCV RNA translation after electroporation of the viral RNA but did not significantly affect replication in JFH1-SGR cells, we sought to compare the effect of siRNA treatment before and after infection with HCVcc JFH1 (Fig. 3C) . The autophagy elongation complex proteins (ATG5-12 and ATG16L1) were also detected in the purified MW from NS4B HA replicon cells, but not in the control extract, thus indicating that the elongation complex is indeed present at the HCV replication site. abstract: Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation. Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication. Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins. Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication. Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype. To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220323/ doi: 10.1038/srep40351 id: cord-323963-whv88ggl author: Fan, Xiaofeng title: Efficient amplification and cloning of near full-length hepatitis C virus genome from clinical samples date: 2006-08-11 words: 5713.0 sentences: 303.0 pages: flesch: 51.0 cache: ./cache/cord-323963-whv88ggl.txt txt: ./txt/cord-323963-whv88ggl.txt summary: Among RNA templates, hepatitis C virus (HCV) represents an excellent example to challenge the potential of LRP technology due to its extensive secondary structures and its difficulty to be readily cultured in vitro. Thus, our LRP protocol could be applied for the amplification of other difficult RNA templates and may facilitate RNA virus research such as linked viral mutations and reverse genetics. In some experiments, we mixed a RT enzyme with Pfu DNA polymerase (Stratagene), a similar strategy as used in long PCR, to improve full-length cDNA synthesis [8] . A representative neighbor-joining (NJ) tree constructed based on HCV E1 domain of 20 clones derived from 9.1 kb LRP product, which was amplified using mixed serum from samples LIV19 and LIV23. A refined long RT-PCR technique to amplify complete viral RNA genome sequences from clinical samples: Application to a novel hepatitis C virus variant of genotype 6 abstract: Abstract Long RT-PCR (LRP) amplification of RNA templates is sometimes difficult compared to long PCR of DNA templates. Among RNA templates, hepatitis C virus (HCV) represents an excellent example to challenge the potential of LRP technology due to its extensive secondary structures and its difficulty to be readily cultured in vitro. The only source for viral genome amplification is clinical samples in which HCV is usually present at low titers. We have created a comprehensive optimization protocol that allows robust amplification of a 9.1kb fragment of HCV, followed by efficient cloning into a novel vector. Detailed analyses indicate the lack of potential LRP-mediated recombination and the preservation of viral diversity. Thus, our LRP protocol could be applied for the amplification of other difficult RNA templates and may facilitate RNA virus research such as linked viral mutations and reverse genetics. url: https://api.elsevier.com/content/article/pii/S0006291X06012964 doi: 10.1016/j.bbrc.2006.06.039 id: cord-314567-purplsjn author: Fernández-Ponce, Cecilia title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells date: 2018-01-04 words: 7978.0 sentences: 382.0 pages: flesch: 41.0 cache: ./cache/cord-314567-purplsjn.txt txt: ./txt/cord-314567-purplsjn.txt summary: HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. As studies using the whole virus do not allow for the elucidation of the specific molecular mechanisms in which each protein is implicated, in this work, we focused on a single viral protein, showing that in CD4 + T cells, HCV core protein mostly localizes in the nucleus and specifically in the nucleolus where it is greatly enriched. abstract: Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4(+) T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells. In order to investigate the intracellular localization of Hepatitis C virus core protein, we have used a lentiviral system to transduce Jurkat T cells and subsequently localize the protein using immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis C virus core protein mostly localizes in the nucleus and specifically in the nucleolus. In addition, we performed pull-down assays combined with Mass Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus core in Jurkat T cells. We found proteins such as NOLC1, PP1γ, ILF3, and C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4(+) T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. Thus, in the current work, we show the ultrastructural localization of Hepatitis C virus core and the first profile of HCV core associated proteins in T cells, and we discuss the functions and interconnections of these proteins in molecular networks where relevant biological modifications have been described upon the expression of Hepatitis C virus core protein. Thereby, the current work constitutes a necessary step toward understanding the mechanisms underlying HCV core mediated alterations that had been described in relevant biological processes in CD4(+) T cells. url: https://www.ncbi.nlm.nih.gov/pubmed/29354102/ doi: 10.3389/fmicb.2017.02595 id: cord-305039-grsv06j7 author: Flego, Michela title: Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases date: 2013-01-04 words: 10985.0 sentences: 476.0 pages: flesch: 37.0 cache: ./cache/cord-305039-grsv06j7.txt txt: ./txt/cord-305039-grsv06j7.txt summary: As for HIV, mAbs directed against spike viral proteins, as well as against host receptors, may act at an early stage of infection by preventing the binding of the virus on the cell surface. In some chronic viral infections, virus-specific immune cells may persist in a ''non-functional'' state, because of an imbalance of immunoregulatory signals involving multiple inhibitory and activating receptors, triggered by soluble factors and/or cell surface ligands. Therapeutic approaches using specific mAbs to block host immunosuppressive molecules (antagonism) or to trigger activating receptors (agonism) may be a valid strategy to restore immune cell function and treat various chronic viral infections. In a proof-of-concept passive immunization trial with humans, it has been demonstrated that a cocktail of the three broadly neutralizing mAbs -2G12, 4E10 and 2F5was able to delay viral rebound in patients whose infections were fully suppressed by antiretroviral treatment before administration of the antibodies [76] . abstract: Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses. This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted. This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact. url: https://www.ncbi.nlm.nih.gov/pubmed/23289632/ doi: 10.1186/1741-7015-11-4 id: cord-317595-siwzjeea author: Forni, Diego title: Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV date: 2018-05-01 words: 9944.0 sentences: 505.0 pages: flesch: 49.0 cache: ./cache/cord-317595-siwzjeea.txt txt: ./txt/cord-317595-siwzjeea.txt summary: Herein, we apply an evolutionary approach to shed light into HCV origin, to analyze its adaptation to human populations, and to verify if the emergence of drug-resistant variants is a result of positive selection. We used Single-Likelihood Ancestor Counting (SLAC) and fixed effects likelihood (FEL) (Kosakovsky Pond and Frost, 2005) to calculate the rates of nonsynonymous and synonymous changes at each site in the structural and in the non-structural region alignments (analyses were performed on alignments split on the basis of the recombination breakpoint detected by GARD). The observation that the positively selected sites are involved in HCV binding and infectivity suggests that hepaciviruses contributed to shape the genetic diversity of CD81 in bats. Using an evolutionary model that accounts for variation in the pressure of natural selection across sites and branches, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago, with a lower bound estimate of ∼5200 years before present. abstract: Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity. url: https://www.ncbi.nlm.nih.gov/pubmed/29765366/ doi: 10.3389/fmicb.2018.00854 id: cord-299719-bvdsz626 author: Fournier, C. title: Are trans‐complementation systems suitable for hepatitis C virus life cycle studies? date: 2013-02-14 words: 4511.0 sentences: 262.0 pages: flesch: 47.0 cache: ./cache/cord-299719-bvdsz626.txt txt: ./txt/cord-299719-bvdsz626.txt summary: Next, the development of cell-culture-grown hepatitis C virus (HCVcc) systems that can assemble and release of infectious viral particles has made it possible to the study structural regions using trans-complementation systems. A series of replicon RNAs carrying mutations (in the NS3, NS4B, NS5A and NS5B regions) that abolished replication were transfected into Huh-7 hepatoma cells harbouring autonomous replicating HCV helper RNAs. In this context, only NS5A mutations in the low complexity sequence I (LCS I) domain have been efficiently rescued ( Table 1 ). These results have clarified the role of Core, p7 and LDs in pseudo-infectious particle production and have indicated that some steps of virus assembly take place around LDs. Various trans-packaging systems have been developed with subgenomic replicons. Trans-encapsidation of hepatitis C virus subgenomic replicon RNA with viral structure proteins Naturally occurring hepatitis C virus subgenomic deletion mutants replicate efficiently in Huh-7 cells and are trans-packaged in vitro to generate infectious defective particles abstract: Complementation is a naturally occurring genetic mechanism that has been studied for a number of plus‐strand RNA viruses. Although trans‐complementation is well documented for Flaviviridae family viruses, the first such system for hepatitis C virus (HCV) was only described in 2005. Since then, the development of a number of HCV trans‐complementation models has improved our knowledge of HCV protein functions and interactions, genome replication and viral particle assembly. These models have also been used to produce defective viruses and so improvements are necessary for vaccine assays. This review provides an update on HCV trans‐complementation systems, the viral mechanisms studied therewith and the production and characterization of trans‐encapsidated particles. url: https://www.ncbi.nlm.nih.gov/pubmed/23490366/ doi: 10.1111/jvh.12069 id: cord-016343-wc3i54fc author: Frese, Michael title: Interferon-Induced Effector Proteins and Hepatitis C Virus Replication date: 2008 words: 10097.0 sentences: 503.0 pages: flesch: 45.0 cache: ./cache/cord-016343-wc3i54fc.txt txt: ./txt/cord-016343-wc3i54fc.txt summary: RdRp, RNA-dependent RNA polymerase; IRES, internal ribosome entry site; 5BSL3.2, stem loop 3.2 within the coding sequence of NS5B normally result in the production of type I IFNs and the subsequent expression of IFN-induced effector proteins, which in turn would establish an antiviral state in the IFN-producing cell itself and in neighboring cells. Since MxA has the ability to efficiently inhibit a variety of different RNA viruses, MxA was the first IFN-induced effector protein to be analyzed for its antiviral activity in the HCV replicon system (Frese et al., 2001) . Rather indirect evidence that the OAS/RNase L pathway may indeed target HCV replication/translation was recently provided by Taguchi and co-workers, who reported that the N-terminal portion of NS5A (amino acids 1 to 148), which lacks the so-called PKR-binding domain, binds to OAS proteins and there by counteract the antiviral activity of IFN-α (Taguchi et al., 2004) . abstract: Hepatitis C virus (HCV) is a small, enveloped RNA virus that is often capable of establishing a persistent infection, which may lead to chronic liver disease, cirrhosis, hepatocellular carcinoma, and eventually death. For more than 20 years, hepatitis C patients have been treated with interferon-alpha (IFN-α). Current treatment usually consists of polyethylene glycol-conjugated IFN-α that is combined with ribavirin, but even the most advanced IFN-based therapies are still ineffective in eliminating the virus from a large proportion of individuals. Therefore, a better understanding of the IFN-induced innate immune response is urgently needed. By using selectable self-replicating RNAs (replicons) and, more recently, recombinant full-length genomes, many groups have tried to elucidate the mechanism(s) by which IFNs inhibit HCV replication. This chapter attempts to summarize the current state of knowledge in this interesting field of HCV research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120596/ doi: 10.1007/978-0-387-71376-2_6 id: cord-284376-plwyjhl8 author: Fu, Xinmiao title: Simulating and forecasting the cumulative confirmed cases of SARS-CoV-2 in China by Boltzmann function-based regression analyses date: 2020-05-31 words: 14726.0 sentences: 782.0 pages: flesch: 49.0 cache: ./cache/cord-284376-plwyjhl8.txt txt: ./txt/cord-284376-plwyjhl8.txt summary: All specimens tested negative by direct examination for PJ, whereas 27 were positive by real-time PCR (BAL, n = 18; sputa, n = 7, and TA, n = 2); Following stringent clinical, microbiological and imaging criteria ( Table 1 ) , PJP was deemed to be the most probable diagnosis in 12 episodes occurring in unique patients. In contrast, corticosteroid use within the month before sampling was not different between The probability of Pneumocystis jirovecii (PJ) pneumonia (PJP) for each patient was retrospectively evaluated by an expert committee including infectious diseases and microbiology specialists at both centers, on the basis of (i) documented PJ presence in respiratory specimens by microscopy; (ii) compatibility of clinical signs and symptoms (at least 2 of the following: subtle onset of progressive dyspnea, pyrexia, nonproductive cough, hypoxaemia and chest pain), (iii) compatible (suggestive) radiological findings (chest radiograph and/or high-resolution computed tomographic scan detection of interstitial opacities and/or diffuse infiltration infiltrates); (iv) complete resolution of symptoms after a full course of anti-PJP treatment; (v) absence of alternative diagnosis. abstract: • Cumulative confirmed cases in China were well fitted with Boltzmann function. • Potential total numbers of confirmed cases in different regions were estimated. • Key dates indicating minimal daily number of new confirmed cases were estimated. • Cumulative confirmed cases of 2003 SARS-CoV were well fitted to Boltzmann function. • The Boltzmann function was, for the first time, applied to epidemic analysis. url: https://api.elsevier.com/content/article/pii/S0163445320300980 doi: 10.1016/j.jinf.2020.02.019 id: cord-271091-ffn59sgf author: Galao, Rui P title: Saccharomyces cerevisiae: a versatile eukaryotic system in virology date: 2007-10-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms. Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production. url: https://www.ncbi.nlm.nih.gov/pubmed/17927824/ doi: 10.1186/1475-2859-6-32 id: cord-298736-9bvyp21d author: Gerold, Gisa title: Decoding protein networks during virus entry by quantitative proteomics date: 2016-06-15 words: 12159.0 sentences: 626.0 pages: flesch: 38.0 cache: ./cache/cord-298736-9bvyp21d.txt txt: ./txt/cord-298736-9bvyp21d.txt summary: In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) . While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM). Of note, high resolution proteomics can not only reveal transient interactions of VAP with enzymes, but also has the potential to identify proteolytic cleavage sites and redox modifications in VAPs. It is conceivable that virus induced protein interactions during entry not only serve to promote the virus uptake pathway, but can also help cloak viruses and lead to immune evasion. abstract: Abstract Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein–protein interactions between viral surface proteins and host proteins as well as secondary host protein–protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future. url: https://api.elsevier.com/content/article/pii/S0168170215300617 doi: 10.1016/j.virusres.2015.09.006 id: cord-321053-lgae22f8 author: Gerold, Gisa title: Opportunities and Risks of Host-targeting Antiviral Strategies for Hepatitis C date: 2013-10-04 words: 9393.0 sentences: 470.0 pages: flesch: 42.0 cache: ./cache/cord-321053-lgae22f8.txt txt: ./txt/cord-321053-lgae22f8.txt summary: Numerous in vitro studies in combination with a growing number of HCV sequencing data from patients undergoing DAA treatment underline that the virus can develop drug-resistance and fitness restoring compensatory mutations [11] . An emerging third group of antivirals, so called hosttargeting antivirals (HTA), may be part of such future combination therapies, in particular as HTAs hold the promise of overcoming some of the caveats of DAAs. HTAs are antibodies, RNAs or small molecules, which interfere with host factors needed for HCV propagation. On the one hand, this demonstrates that HCV can in theory evade HTA therapy by mutating the viral binding partner of the targeted host factor and in fact suggests a low genetic barrier to resistance. Targeting HCV RNA Replication: Phosphatidylinositol 4-kinase III alpha (PI4KIIIα) Genome wide RNA interference screens and in depth cell culture replication assays with HCV replicons and full length infectious virus have revealed numerous additional host dependency factors, that could in principle serve as antiviral targets [99] [100] [101] [102] [103] [104] [105] [106] [107] . abstract: Hepatitis C virus (HCV) infects more than 2 % of the world population with highest prevalence in parts of Africa and Asia. Past standard of care using interferon α and ribavirin had adverse effects and showed modest efficacy for some HCV genotypes spurring the development of direct acting antivirals (DAAs). Such DAAs target viral proteins and are thus better tolerated but they suffer from emergence of vial resistance. Furthermore, DAAs are often HCV genotype specific. Novel drug candidates targeting host factors required for HCV propagation, so called host-targeting antivirals (HTAs), promise to overcome both caveats. The genetic barrier to resistance is usually considered to be high for HTAs and all HCV genotypes presumably use the same host factors. Recent data, however, challenge these assumptions, at least for some HTAs. Here, we highlight the most important host-targeting strategies against hepatitis C and critically discuss their opportunities and risks. url: https://www.ncbi.nlm.nih.gov/pubmed/32214912/ doi: 10.1007/s11901-013-0187-1 id: cord-293857-o8rlqsq5 author: Ghosh, Arun K. title: Organic Carbamates in Drug Design and Medicinal Chemistry date: 2015-01-07 words: 18165.0 sentences: 1121.0 pages: flesch: 41.0 cache: ./cache/cord-293857-o8rlqsq5.txt txt: ./txt/cord-293857-o8rlqsq5.txt summary: Also, we will outline successful designs of organic carbamates, including a variety of cyclic ether-derived carbamates, as suitable amide bond surrogates leading to a wide range of novel organic carbamates as potent HIV-1 protease, βsecretase, serine protease, and cysteine protease inhibitors. 172−174 A number of FDA-approved HIV protease inhibitor drugs contain an important carbamate functionality. 179, 230 Further development of carbamate-derived novel HIV-1 protease inhibitors is shown in Figure 12 . This backbone binding strategy to combat drug resistance led to the development of a series of very potent carbamate-derived protease inhibitors. Carbamate derivative 281 (Figure 24 ), a diphenyl phosphonate ester containing a Cbz group and bearing a single amino acid side chain, showed very good inhibitory activity against human plasma kallikrein, useful for the treatment of hereditary angioedema. Design and synthesis of potent HIV-1 protease inhibitors incorporating hexahydrofuropyranol-derived high affinity P(2) ligands: structure-activity studies and biological evaluation abstract: [Image: see text] The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug–target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry. url: https://doi.org/10.1021/jm501371s doi: 10.1021/jm501371s id: cord-293790-7hyelm88 author: Guévin, Carl title: Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection date: 2010-09-01 words: 5267.0 sentences: 290.0 pages: flesch: 54.0 cache: ./cache/cord-293790-7hyelm88.txt txt: ./txt/cord-293790-7hyelm88.txt summary: title: Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection To identify novel cellular factors that may play an essential role in HCV RNA replication, we have previously screened a human liver cDNA library for proteins interacting with the HCV NS5B RNAdependent RNA polymerase (RdRp). Here we report that ATG5, a protein required for the formation of DMV in embryonic stem cell (Mizushima et al., 2001) , specifically interacts with HCV NS5B. As a control, a panel of proteins (RAR-β, RAR-α, HCV core, and nonstructural protein: NS3 prot , NS3 hel , NS4A, and NS4B) cloned in the GAL4 DNA binding domain was tested for interaction with ATG5. A. Soluble yeast extracts containing NS5BΔ21 (N-terminal c-myc tag) and ATG5 (N-terminal HA tag) were incubated with different monoclonal antibodies and the immunoprecipitates were pulled down using protein A/G beads. abstract: Autophagy is an important cellular process by which ATG5 initiates the formation of double membrane vesicles (DMVs). Upon infection, DMVs have been shown to harbor the replicase complex of positive-strand RNA viruses such as MHV, poliovirus, and equine arteritis virus. Recently, it has been shown that autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Here, we identified ATG5 as an interacting protein for the HCV NS5B. ATG5/NS5B interaction was confirmed by co-IP and metabolic labeling studies. Furthermore, ATG5 protein colocalizes with NS4B, a constituent of the membranous web. Importantly, immunofluorescence staining demonstrated a strong colocalization of ATG5 and NS5B within perinuclear regions of infected cells at 2 days postinfection. However, colocalization was completely lacking at 5 DPI, suggesting that HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Finally, inhibition of autophagy through ATG5 silencing blocks HCV replication. url: https://www.sciencedirect.com/science/article/pii/S0042682210003764 doi: 10.1016/j.virol.2010.05.032 id: cord-314148-5xisw9au author: Hasony, Hassan J. title: Prevalence of human coronavirus antibody in the population of southern iraq date: 2005-12-06 words: 2761.0 sentences: 122.0 pages: flesch: 53.0 cache: ./cache/cord-314148-5xisw9au.txt txt: ./txt/cord-314148-5xisw9au.txt summary: Several reports have analyzed the extent of infections in various populations in America and Europe by estimates of HCV antibodies in sera from patients and volunteers [Bradburne and Somerset, 1972; Candeias et al, 1970; Cavallaro and Monto, 1970 ; Hamre and Beem, 1972; Hendley et al, 1972; Hovi et al, 1979 ; Kaye et al, 1971; McIntosh et al, 1970; Zakstelskaya et al, 19721 . In this study representative viruses from the 229E and OC43 antigenic groups were used in ELISA to measure the antibodies to these viruses in sera collected during the winter from patients and volunteers from the Basrah area of Southern Iraq. 67 random sera were collected from healthy adult volunteers at the Common Cold Unit, Salisbury, before inoculation with any viruses, and tested by ELISA for antibodies to HCV 229E and CV Paris. abstract: Sera from adults in Southern Iraq were collected during winter and screened by an enzyme–linked immunosorbent assay for the presence of antibodies to the two antigenic groups of human coronaviruses, the 229E and the OC43 groups: 91% of the sera had antibodies to at least one of the groups, whereas 4 and 5% of the sera had antibodies to only the 229E or OC43 groups, respectively. There was significant correlation between the levels of antibody to the 229E and OC43 group coronaviruses in these sera. url: https://www.ncbi.nlm.nih.gov/pubmed/7097257/ doi: 10.1002/jmv.1890090308 id: cord-312080-pu6m4qad author: He, Bing title: Three-dimensional cell culture models for investigating human viruses date: 2016-10-27 words: 9036.0 sentences: 454.0 pages: flesch: 38.0 cache: ./cache/cord-312080-pu6m4qad.txt txt: ./txt/cord-312080-pu6m4qad.txt summary: This review focuses on the recent progress of human virological research with 3D cell culture models, including human viral growth, replication, proliferation, infection, viral life cycle, virus-host interaction and the development of antiviral drugs. A multitude of research has shown that RWV-derived models utilizing human cells are a valuable tool for investigating viral growth, replication, viral infection, viral entry, the viability of virions and virus-host interaction (Margolis et al., 1997; Long et al., 1998; Nickerson et al., 2007; Straub et al., 2007; Barrila et al., 2010; Berto et al., 2013; Goodwin et al., 2015) . As keratinocytes are the main target cells for productive infection in vivo for VZV, characterization of viral replication in organotypic raft cultures of these cells represents a very relevant model for studying virus-host cell interactions and antiviral agents (Andrei et al., 2005) . abstract: Three-dimensional (3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover, these models bridge the gap between traditional two-dimensional (2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition, 3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models. url: https://www.ncbi.nlm.nih.gov/pubmed/27822716/ doi: 10.1007/s12250-016-3889-z id: cord-006129-5rog0s98 author: Hemida, Maged Gomaa title: Exploiting the Therapeutic Potential of MicroRNAs in Viral Diseases: Expectations and Limitations date: 2012-08-16 words: 7443.0 sentences: 508.0 pages: flesch: 50.0 cache: ./cache/cord-006129-5rog0s98.txt txt: ./txt/cord-006129-5rog0s98.txt summary: [12] Answering back, certain host miRNAs alter the cell gene expression to defend the cells against the viral infection by interfering with viral proteins or other cellular factors as a type of immune response against these particular viruses. [40] These virus-encoded miRNAs play important roles in the establishment of latent infection, as well as the pathogenesis of virally induced diseases. According to the most recent studies, herpesviruses utilize their encoded miRNAs in a wide range of biologic functions, such as inhibition of apoptosis, immune evasion, control of cellular proliferation, and regulation of viral replication. [58] Downregulation of UL114 protein, using miR-UL112-1, results in inhibition of viral DNA replication and subsequently triggers the latent phase of infection, making the virus able to evade the host immune system. abstract: New therapeutic approaches are urgently needed for serious diseases, including cancer, cardiovascular diseases, viral infections, and others. A recent direction in drug development is the utilization of nucleic acidbased therapeutic molecules, such as antisense oligonucleotides, ribozymes, short interfering RNA (siRNA), and microRNA (miRNA). miRNAs are endogenous, short, non-coding RNA molecules. Some viruses encode their own miRNAs, which play pivotal roles in viral replication and immune evasion strategies. Conversely, viruses that do not encode miRNAs may manipulate host cell miRNAs for the benefits of their replication. miRNAs have therefore become attractive tools for the study of viral pathogenesis. Lately, novel therapeutic strategies based on miRNA technology for the treatment of viral diseases have been progressing rapidly. Although this new generation of molecular therapy is promising, there are still several challenges to face, such as targeting delivery to specific tissues, avoiding off-target effects of miRNAs, reducing the toxicity of the drugs, and overcoming mutations and drug resistance. In this article, we review the current knowledge of the role and therapeutic potential of miRNAs in viral diseases, and discuss the limitations of these therapies, as well as strategies to overcome them to provide safe and effective clinical applications of these new therapeutics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099301/ doi: 10.1007/bf03256383 id: cord-006061-z9r5htm9 author: Hu, Bo title: HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation date: 2016-06-17 words: 4242.0 sentences: 242.0 pages: flesch: 53.0 cache: ./cache/cord-006061-z9r5htm9.txt txt: ./txt/cord-006061-z9r5htm9.txt summary: Altogether, we provide a mechanism by which NS4B induces cell transformation through its PBM, which specifically interacts with the PDZ domains of Scribble and targets Scribble for degradation. Our previous work has shown that NS4B expression activates unfolded protein response (UPR), ER overload response, and NF-κB pathway in human hepatic cells, which could contribute to HCV replication and pathogenesis [11] [12] [13] . As shown in Fig. 5a , expression of HCV NS4B led to reduced USP14 protein levels in both 293T cells and HepG2 cells especially at 48-h post-transfection, indicating that HCV NS4B activates the proteasome-ubiquitin pathway. In this study, we provided a plausible mechanism that NS4B induces cell transformation by degrading the tumor-suppressor protein, Scribble, through the interaction between NS4B PBM and Scribble PDZ domains. The NS4B PBM-Scribble PDZ interaction is important for colony formation of transfected cells, indicating that NS4B PBM contributes to HCV pathogenesis and cellular transformation by inducing Scribble degradation. abstract: Hepatitis C virus (HCV) nonstructural protein 4B (NS4B) is a multi-transmembrane protein, but little is known about how NS4B contributes to HCV replication and tumorigenesis. Its C-terminal domain (CTD) has been shown to associate with intracellular membrane, and we have previously shown that NS4B CTD contains a class I PDZ-binding motif (PBM). Here, we demonstrated that NS4B PBM interacts with the PDZ-containing tumor suppressor protein, Scribble, using immunofluorescence and co-immunoprecipitation assays, and this interaction requires at least three contiguous PDZ domains of Scribble. In addition, NS4B PBM specifically induced Scribble degradation by activating the proteasome-ubiquitin pathway. Similar Scribble degradation was also observed in HCV-infected cells, suggesting NS4B could work in the context of HCV. Finally, NS4B PBM mutants showed reduced colony formation capacity compared with its wild-type counterpart, indicating that NS4B PBM plays important roles in NS4B-mediated cell transformation. Altogether, we provide a mechanism by which NS4B induces cell transformation through its PBM, which specifically interacts with the PDZ domains of Scribble and targets Scribble for degradation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097421/ doi: 10.1007/s13277-016-5100-4 id: cord-015941-4fz79wzf author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2018-11-10 words: 7210.0 sentences: 381.0 pages: flesch: 50.0 cache: ./cache/cord-015941-4fz79wzf.txt txt: ./txt/cord-015941-4fz79wzf.txt summary: Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus''s genetic material instead of waiting for the body''s response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [21] , thus further improving blood safety. One reason for this is that currently available blood screening technologies detect core antibodies or surface antigens, which appear up to 8 weeks after infection. The anti-HBc test developed in 1987 detects an antibody to the hepatitis B virus that is produced during and after infection. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing abstract: Blood product safety is a high priority for manufacturing industries, hospitals, and regulatory agencies. An important step in ensuring safety is the screening of donated blood for infectious diseases. Molecular technologies for screening infectious diseases have improved remarkably over the years. Molecular biological assay significantly reduced the risk of transfusion-transmitted infections. Unlike previous methods, molecular technologies for screening infectious diseases are specific, efficient, easy to use, and economical. A new era in molecular biology is coming to the field of blood safety. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120069/ doi: 10.1007/978-3-319-95111-9_2 id: cord-017948-fqhl1qb4 author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2012-04-05 words: 7304.0 sentences: 372.0 pages: flesch: 54.0 cache: ./cache/cord-017948-fqhl1qb4.txt txt: ./txt/cord-017948-fqhl1qb4.txt summary: Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus''s genetic material instead of waiting for the body''s response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [ 19 ] , thus further improving blood safety. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-ampli fi cation testing abstract: The Food and Drug Administration (FDA) is responsible for ensuring the safety of the more than 15 million units of blood and blood components donated each year in the United States. “Blood banking has become a manufacturing industry, an industry that must conform to high standards and quality control requirements comparable to those of pharmaceutical companies or other regulated industries,” said David A. Kessler, MD, former FDA commissioner [1]. Screening donated blood for infectious diseases that can be transmitted through blood transfusion is a very important step in ensuring safety. The United States has the safest blood supply in the world [1] and the FDA is striving to keep it safe by decreasing the risk of infectious disease transmission. The regulatory agency is continuously updating its requirements and standards for collecting and processing blood. As mentioned earlier, an important step in ensuring safety is the screening of donated blood for infectious diseases. In the United States, tests for infectious diseases are routinely conducted on each unit of donated blood, and these tests are designed to comply with regulatory requirements (Table 28.1). The field of clinical microbiology and virology are now focusing on molecular technology. Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. It is time for all blood safety procedures to include molecular detection techniques. This approach can significantly aid in blood safety to reduce the risk of transmission of serious disease by transfusion. This chapter reviews the current antigen/antibody-based technology, molecular biological technology, and published regulatory policy data for blood safety. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122649/ doi: 10.1007/978-1-4614-3970-7_28 id: cord-003407-f5v3hhr8 author: Hung, Ting-Chun title: Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date: 2018-11-27 words: 4790.0 sentences: 203.0 pages: flesch: 41.0 cache: ./cache/cord-003407-f5v3hhr8.txt txt: ./txt/cord-003407-f5v3hhr8.txt summary: Thus, RC''s anti-HCV activity appeared strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. Viruses 2018, 10, x FOR PEER REVIEW 6 of 12 strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. To further characterize the mechanism(s) underlying RC''s anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. To further characterize the mechanism(s) underlying RC''s anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. abstract: Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases. Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection. Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV. Herein, we investigated the anti-HCV activity of the methanolic extract from Rhizoma coptidis (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects. Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations. In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV. Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes. Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315547/ doi: 10.3390/v10120669 id: cord-337285-t6qr41wc author: Ikeda, Masanori title: Modulation of host metabolism as a target of new antivirals() date: 2007-10-10 words: 8180.0 sentences: 466.0 pages: flesch: 46.0 cache: ./cache/cord-337285-t6qr41wc.txt txt: ./txt/cord-337285-t6qr41wc.txt summary: Using cell culture systems, several cellular proteins have been identified as effective molecules for HCV RNA replication (Table 1) . [66] reported that lovastatin (LOV), one of the HMG-CoA reductase inhibitors, inhibited HCV RNA replication in HCV replicon-harboring cells. Depletion of the GGPP by statins may inhibit the geranylgeranylation of cellular proteins such as FBL2 and cause the anti-HCV effect in the cells. During the development of IFN therapy for patients with CH-C, the lack of a robust method of HCV RNA replication in cell culture has hampered research into the HCV life cycle and the discovery of potent new anti-HCV reagents. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells abstract: The therapy for chronic hepatitis C (CH–C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH–C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism. url: https://www.sciencedirect.com/science/article/pii/S0169409X07001317 doi: 10.1016/j.addr.2007.03.021 id: cord-334493-rt7gqiev author: Ikejiri, Masahiro title: 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents date: 2007-11-15 words: 4869.0 sentences: 242.0 pages: flesch: 61.0 cache: ./cache/cord-334493-rt7gqiev.txt txt: ./txt/cord-334493-rt7gqiev.txt summary: On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC(50) = 47.2 μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. The resultant residue was purified by silica gel column chromatography (ethyl acetate/hexane, To a stirred solution of 31 (200 mg, 0.56 mmol) in dioxane (1 mL) was added 50% dimethylamine-water solution (8 mL) at room temperature, and the mixture was stirred overnight at the same temperature. abstract: On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Among these, several 5′-O-masked analogues of 6-chloropurine-2′-deoxyriboside (e.g., 5′-O-benzoyl, 5′-O-p-methoxybenzoyl, and 5′-O-benzyl analogues) were found to exhibit effective anti-HCV activity. In particular, the 5′-O-benzoyl analogue exhibited the highest potency with an EC(50) of 6.1 μM in a cell-based HCV replicon assay. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC(50) = 47.2 μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. Presently, we hypothesize two roles for the 5′-O-masked analogues: One is the role as an anti-HCV agent by itself, and the other is as a prodrug of its 5′-O-demasked (deprotected) derivative. url: https://www.ncbi.nlm.nih.gov/pubmed/17766124/ doi: 10.1016/j.bmc.2007.08.025 id: cord-007305-pkjfnhro author: Iosub, Silvia title: Leukonychia Partialis in Kawasaki Disease date: 1984-10-17 words: 1083.0 sentences: 68.0 pages: flesch: 57.0 cache: ./cache/cord-007305-pkjfnhro.txt txt: ./txt/cord-007305-pkjfnhro.txt summary: COLLEAGUES -Some areas in the northern part of the Israel desert (Negev) are known to be endemic for Borrelia recurrentis infection [1] (tick-borne relapsing fever). None of them developed overt symptoms and signs of tick-borne relapsing fever as observed in the subjects from groups I and II. Our patients had nail abnormalities typical for leukonychia partialis of the acquired type, since color changes had not been noted before the present illness and were transient. We would welcome correspondence from others who have seen nail color abnormalities in Kawasaki disease. COLLEAGUES -We examined paired sera from 62 infants with acute non bacterial gastroenteritis and from 50 age-matched controls (admitted to the hospital for nondiarrheal diseases) for antibody to human coronavirus (HCV) OC43 and neonatal-calf diarrhea coronavirus (NCDCY). Convalescent-phase sera from all the patients positive for excretion of coronavirus-like particles in stools, and seronegative for previous HCV OC43 infections, reacted by IEM with HECY-24 and HECV-35 and, to a lesser extent, with HCY OC43. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110293/ doi: 10.1093/infdis/150.4.617-a id: cord-284978-vh1x6pg9 author: Jang, Hongje title: Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide date: 2013-02-18 words: 2968.0 sentences: 160.0 pages: flesch: 53.0 cache: ./cache/cord-284978-vh1x6pg9.txt txt: ./txt/cord-284978-vh1x6pg9.txt summary: Herein, we developed a multiplexed helicase assay based on graphene oxide (GO) for high-throughput screening of inhibitors of HCV NS3 helicase and severe acute respiratory syndrome coronavirus (SARS CoV) helicase. [10] Herein, we show that the GOHA can be used for measuring the activities of HCV NS3 helicase and SARS CoV helicase in a single mixed solution using two distinct DNA substrates tethered to different fluorophores, and furthermore, for multiplexed high-throughput screening to discover highly selective small-molecule inhibitors of these helicases ( Figure 1 ). A 96-well plate mGOHA was used to screen a 10 000 compound library to discover inhibitors of SARS CoV helicase and HCV NS3 helicase (Figure 3) . [17] Two compounds, antiHCV-Hel-2 and -3, showed a dose-dependent decrease in the Luc/MTT values with the respective half-maximal effective concentrations (EC 50 ) of 188.1 AE 32.6 and 56.8 AE 7.4 mm, indicating that they dose-dependently blocked HCV RNA replication in the cultured Huh-7 cells (Figure 5 b,c) . abstract: Ein einfaches Testsystem auf der Basis von Graphenoxid (GO) ermöglicht das Screening selektiver Inhibitoren einer Helicase des Hepatitis‐C‐Virus (HCV) zusammen mit Inhibitoren eines SARS‐Coronavirus (SARS‐CoV) (siehe Schema). In einem einzelnen Screen wurden fünf hochselektive Inhibitoren der HCV‐Helicase gefunden, die ortholog zur SARS‐CoV‐Helicase sind. Einige dieser Treffer wurden mit dem gleichen GO‐Assay validiert.[Image: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/32313317/ doi: 10.1002/ange.201209222 id: cord-307556-k2lavvca author: Jang, Hongje title: Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide date: 2013-02-18 words: 2983.0 sentences: 154.0 pages: flesch: 53.0 cache: ./cache/cord-307556-k2lavvca.txt txt: ./txt/cord-307556-k2lavvca.txt summary: Herein, we developed a multiplexed helicase assay based on graphene oxide (GO) for high-throughput screening of inhibitors of HCV NS3 helicase and severe acute respiratory syndrome coronavirus (SARS CoV) helicase. [10] Herein, we show that the GOHA can be used for measuring the activities of HCV NS3 helicase and SARS CoV helicase in a single mixed solution using two distinct DNA substrates tethered to different fluorophores, and furthermore, for multiplexed high-throughput screening to discover highly selective small-molecule inhibitors of these helicases ( Figure 1 ). A 96-well plate mGOHA was used to screen a 10 000 compound library to discover inhibitors of SARS CoV helicase and HCV NS3 helicase (Figure 3) . [17] Two compounds, antiHCV-Hel-2 and -3, showed a dose-dependent decrease in the Luc/MTT values with the respective half-maximal effective concentrations (EC 50 ) of 188.1 AE 32.6 and 56.8 AE 7.4 mm, indicating that they dose-dependently blocked HCV RNA replication in the cultured Huh-7 cells (Figure 5 b,c) . abstract: A GO‐to solution: A simple graphene oxide (GO)‐based assay to screen for selective inhibitors of a hepatitis C virus (HCV) helicase along with inhibitors of a severe acute respiratory syndrome coronavirus (SARS CoV) helicase was tested (see scheme). A single screen found five inhibitors highly selective for the HCV helicase orthologous to the SARS CoV helicase. Some of these hits were validated using the same GO‐based assay.[Image: see text] url: https://doi.org/10.1002/anie.201209222 doi: 10.1002/anie.201209222 id: cord-285868-fz5utxss author: Jheng, Jia-Rong title: ER stress, autophagy, and RNA viruses date: 2014-08-05 words: 9345.0 sentences: 480.0 pages: flesch: 38.0 cache: ./cache/cord-285868-fz5utxss.txt txt: ./txt/cord-285868-fz5utxss.txt summary: In addition to regulation of cell death, it is reported that HCV induces the expression of CHOP at mRNA and protein levels and is correlated with autophagy induction; knockdown of CHOP not only increases HCV PAMP-mediated innate immune activation, but also elevates its inhibitory effect on virus replication (Ke and Chen, 2011) . Overexpression of HCV E1 and/or E2 induces the expression of CHOP in a PERK-dependent manner (Chan and Egan, 2005) ; while upon HCV infection, CHOP protein is upregulated by PERK, activating transcription factor (ATF6), and inositol-requiring transmembrane kinase/endonuclease 1 (IRE1) collectively. It was reported that rotavirus NSP4 viroporin initiates autophagy to transport viral proteins to sites of virus replication for assembly of mature particles, which involves an increase of cytoplasmic calcium and subsequent activation of the CaMKK-β-AMPK pathway. Regulated IRE1-dependent decay pathway is activated during Japanese encephalitis virus-induced unfolded protein response and benefits viral replication abstract: Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/25140166/ doi: 10.3389/fmicb.2014.00388 id: cord-324984-ojrpsdt9 author: Ji, Xingyue title: Medicinal chemistry strategies toward host targeting antiviral agents date: 2020-02-14 words: 16814.0 sentences: 825.0 pages: flesch: 43.0 cache: ./cache/cord-324984-ojrpsdt9.txt txt: ./txt/cord-324984-ojrpsdt9.txt summary: In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. 3 Altogether, targeting host factors is a very promising strategy with possibility to address the critical challenges faced with the DAAs. In this review, we summarize the recent advances made in HTAs from a medicinal chemistry standpoint, and the host targets are generally classified into three different categories based on the development stage of their corresponding inhibitors/modulators, namely the ones which reached Food and Drug Administration (FDA) approval, that have entered clinical trials and those in preclinical studies. abstract: Direct‐acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow‐spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad‐spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed. url: https://doi.org/10.1002/med.21664 doi: 10.1002/med.21664 id: cord-284693-mgpxnnk0 author: Jothimani, Dinesh title: Post Liver transplant recurrent and de novo viral infections date: 2020-09-26 words: 6339.0 sentences: 366.0 pages: flesch: 41.0 cache: ./cache/cord-284693-mgpxnnk0.txt txt: ./txt/cord-284693-mgpxnnk0.txt summary: Advanced recipient age, diabetes mellitus, severe liver disease (Child Pugh >10), IL-28B polymorphism, high HCV RNA >10 7 IU/ml, ischemic/reperfusion injury, CMV, donor age >65 years, cold ischaemic time over 8 hours and warm ischemia over 90 minutes, marginal graft, DCD donor, higher immunosuppression in particular high dose corticosteroids for acute cellular rejection, use of anti-thymocyte globulin were significantly associated with rHCV in the liver allograft 15, 16 . Initial studies with sofosbuvir and ribavirin combination therapy for post-transplant rHCV showed poor drug tolerance, however, the main adverse event was anaemia related to ribavirin in 62% of patients, and subsequent hepatic decompensation related to the low haemoglobin 38 . A study by Pellicelli et al., showed significant adverse events including hepatic decompensation and 25% mortality in those with advanced disease following treatment with daclatasvir and sofosbuvir for post-transplant rHCV 51 . abstract: Survival following liver transplantation has changed dramatically owing to improvement in surgical techniques, peri-operative care and optimal immunosuppressive therapy. Post-Liver transplant (LT) de novo or recurrent viral infection continues to cause major allograft dysfunction, leading to poor graft and patient survival in untreated patients. Availability of highly effective antiviral drugs has significantly improved post-LT survival. Patients transplanted for chronic hepatitis B infection should receive life-long nucleos(t)ide analogues, with or without HBIg for effective viral control. Patients with chronic hepatitis C should be commenced on directly acting antiviral (DAA) drugs prior to transplantation. DAA therapy for post-LT recurrent hepatitis C infection is associated with close to 100% sustained virological response (SVR), irrespective of genotype. De novo chronic Hepatitis E infection is an increasingly recognised cause of allograft dysfunction in LT recipients. Untreated chronic HEV infection of the graft may lead to liver fibrosis and allograft failure. Similarly, CMV and EBV can reactivate leading to systemic illness following liver transplantation. With COVID-19 pandemic, post-transplant patients are at risk of SARS-Co-V2 infection. Majority of the LT recipients require hospitalisation, and the mortality in this population is around 20%. Early recognition of allograft dysfunction and identification of viral aetiology is essential in the management of post-LT de novo or recurrent infections. Optimising immunosuppression is an important step in reducing the severity of allograft damage in the treatment of post-transplant viral infections. Viral clearance or control can be achieved by early initiation of high potency antiviral therapy. url: https://doi.org/10.1016/j.bpg.2020.101689 doi: 10.1016/j.bpg.2020.101689 id: cord-311823-85wj08gr author: Katze, Michael G. title: Innate immune modulation by RNA viruses: emerging insights from functional genomics date: 2008 words: 9154.0 sentences: 392.0 pages: flesch: 36.0 cache: ./cache/cord-311823-85wj08gr.txt txt: ./txt/cord-311823-85wj08gr.txt summary: In this section, we review recent studies in which genomic approaches have been used to provide new information on how viruses trigger and regulate innate immune pathways, and to evaluate the use of type I IFN-based therapy as a means to enhance the innate immune response to HCV. In RIg-I-deficient cells, influenza virus fails to elicit the expression of IFNβ and of many ISgs, including key antiviral mediators such as IRF3, STAT1 (signal transducer and activator of transcription 1), IFIT1 (IFN-induced protein with tetratricopeptide repeats 1; also known as ISg56) and ISg54 (also known as IFIT2). Although these studies have provided considerable information regarding the genes activated downstream of TlR activation, it will be advantageous to extend genomic analyses in the context of viral infection using cells lacking the expression of specific TlRs. The ability of a virus to establish an infection depends, at least to some extent, on its ability to block the host innate immune response or to modulate the activity of antiviral effector proteins. abstract: Although often encoding fewer than a dozen genes, RNA viruses can overcome host antiviral responses and wreak havoc on the cells they infect. Some manage to evade host antiviral defences, whereas others elicit an aberrant or disproportional immune response. Both scenarios can result in the disruption of intracellular signalling pathways and significant pathology in the host. Systems-biology approaches are increasingly being used to study the processes of viral triggering and regulation of host immune responses. By providing a global and integrated view of cellular events, these approaches are beginning to unravel some of the complexities of virus–host interactions and provide new insights into how RNA viruses cause disease. url: https://doi.org/10.1038/nri2377 doi: 10.1038/nri2377 id: cord-349358-leicos9j author: Ketzinel‐Gilad, Mali title: RNA interference for antiviral therapy date: 2006-06-16 words: 12734.0 sentences: 684.0 pages: flesch: 44.0 cache: ./cache/cord-349358-leicos9j.txt txt: ./txt/cord-349358-leicos9j.txt summary: During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Likewise, expression vectors of siRNAs specific for two different regions of the WNV genome protected 293T cells from WNV infection, and significantly reduced viral RNA replication and virus production [35] . From the reports on the use of siRNA against human viral pathogens causing acute disease, we could learn that for each specific pathogen infecting a specific cell lineage or tissue, we would probably need to perform an indepth assessment, with proper in vitro and in vivo models, and develop specific delivery systems. The most challenging part of RNAi approaches for chronic viral infections is to design the best delivery method that would facilitate the targeting of the specific organ/cells with the appropriate expression system, for durable intracellular levels of gene-silencing effect. abstract: Silencing gene expression through a process known as RNA interference (RNAi) has been known in the plant world for many years. In recent years, knowledge of the prevalence of RNAi and the mechanism of gene silencing through RNAi has started to unfold. It is now believed that RNAi serves in part as an innate response against invading viral pathogens and, indeed, counter silencing mechanisms aimed at neutralizing RNAi have been found in various viral pathogens. During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Furthermore, it is now apparent that in in vitro and in some in vivo models, the prospects for this technology in developing therapeutic applications are robust. However, many key questions and obstacles in the translation of RNAi into a potential therapeutic platform still remain, including the specificity and longevity of the silencing effect, and, most importantly, the delivery of the dsRNA that induces the system. It is expected that for the specific examples in which the delivery issue could be circumvented or resolved, RNAi may hold promise for the development of gene‐specific therapeutics. Copyright © 2006 John Wiley & Sons, Ltd. url: https://www.ncbi.nlm.nih.gov/pubmed/16779870/ doi: 10.1002/jgm.929 id: cord-291321-ao80xk11 author: Khan, Mohsin title: Mitochondrial dynamics and viral infections: A close nexus date: 2015-10-31 words: 9764.0 sentences: 538.0 pages: flesch: 26.0 cache: ./cache/cord-291321-ao80xk11.txt txt: ./txt/cord-291321-ao80xk11.txt summary: Hepatitis C virus [8, 9] Enhanced fission and mitophagy Core, E1-E2 Activation of Drp-1, and mitochondrial translocation of Parkin Inhibition of apoptosis and innate immune response, facilitates persistent infection Pseudorabies virus [136] Fragmented mitochondria Glycoprotein B (GB) Altered functioning of Miro protein Affects intracellular calcium signaling and mitochondrial motility Human cytomegalovirus [130] Enhanced fission vMIA Affects mechanism of Bax Inhibition of apoptosis Epstein-Barr virus [128] Enhanced fission LMP2A Up regulation of Drp-1 Cell migration and apoptosis Hepatitis B virus [7] Enhanced fission and mitophagy HBx Parkin and PINK1 up-regulation and Drp-1 phosphorylation Inhibition of apoptosis and innate immune response, facilitates persistent infection Influenza A virus [98] Induction of mitophagy Unknown The NOD2 and RIPK2 promote ULK1 phosphorylation to induce mitophagy Inhibits inflammasome activation and reduces disease severity Influenza A virus [137, 138] Induction of mitochondrial fragmentation inhibition of mitochondrial β-oxidation of fatty acids [109] . abstract: Abstract Viruses manipulate cellular machinery and functions to subvert intracellular environment conducive for viral proliferation. They strategically alter functions of the multitasking mitochondria to influence energy production, metabolism, survival, and immune signaling. Mitochondria either occur as heterogeneous population of individual organelles or large interconnected tubular network. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections, and is dynamically maintained by mitochondrial fission and fusion. Mitochondrial dynamics in tandem with mitochondria-selective autophagy ‘mitophagy’ coordinates mitochondrial quality control and homeostasis. Mitochondrial dynamics impacts cellular homeostasis, metabolism, and innate-immune signaling, and thus can be major determinant of the outcome of viral infections. Herein, we review how mitochondrial dynamics is affected during viral infections and how this complex interplay benefits the viral infectious process and associated diseases. This article is part of a Special Issue entitled: Mitophagy. url: https://www.sciencedirect.com/science/article/pii/S0167488915000099 doi: 10.1016/j.bbamcr.2014.12.040 id: cord-017506-t86v3zw3 author: Knox, Tamsin A. title: Alcohol, HIV/AIDS, and Liver Disease date: 2012-04-27 words: 7643.0 sentences: 353.0 pages: flesch: 37.0 cache: ./cache/cord-017506-t86v3zw3.txt txt: ./txt/cord-017506-t86v3zw3.txt summary: Cardiovascular disease is likely due to a combination of additional risk factors found in HIV infection [ 26 ] including (1) chronic in fl ammation from HIV viral replication and subsequent immunode fi ciency [ 134 ] , (2) the effect of chronic in fl ammation on serum lipid levels [ 133 ] , (3) the metabolic effects of certain classes of antiretroviral medications [ 131, 133 ] , (4) increased prevalence of insulin resistance [ 135 ] , and (5) increased translocation of bacteria across the small intestine into the bloodstream as a result of immunode fi ciency [ 136 ] . Freiberg et al., studying the VACS Cohort, found that the risk of cardiovascular disease was increased (OR 1.55, 95% CI 1.07-2.23) in HIV-infected men with alcohol abuse or dependence, when controlled for cardiac risk factors, ART use, and CD4 count [ 8 ] . abstract: Globally, there are over 33 million persons living with HIV/AIDS resulting in 1.8 million deaths annually. While the rate of HIV transmission is slowing, it is estimated that 2.6 million new infections occur yearly [1]. In the United States, there are approximately 1.2 million living with HIV/AIDS, with 50,000 new HIV infections and 17,000 deaths from the disease annually [2]. For those who can obtain effective antiretroviral therapy (ART), HIV/AIDS has become a chronic disease with life expectancies over 30 years [3]. Research in the last 10 years has revealed the importance of alcohol in the HIV/AIDS epidemic. Alcohol use, in moderate or hazardous amounts, has been associated with increased acquisition of HIV infection, progression of HIV infection, deleterious effects on HIV treatment, and acceleration in the comorbidities of HIV infection [4–9]. Yet alcohol remains the “forgotten drug” of the HIV/AIDS epidemic [10]. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122083/ doi: 10.1007/978-1-62703-047-2_23 id: cord-005138-u2lwgyyf author: Kou, Yi-Hen title: Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A date: 2006-08-23 words: 6110.0 sentences: 363.0 pages: flesch: 51.0 cache: ./cache/cord-005138-u2lwgyyf.txt txt: ./txt/cord-005138-u2lwgyyf.txt summary: title: Hepatitis C virus NS4A inhibits cap-dependent and the viral IRES-mediated translation through interacting with eukaryotic elongation factor 1A In this study, we have demonstrated that NS4A specifically interacted with eukaryotic elongation factor 1A (eEF1A) and inhibited both cap-and HCV IRES-dependent protein synthesis. To perform translation inhibition assay in culture cells, plasmids encoding V5-tagged HCV nonstructure proteins NS3, NS4A, NS4B, and NS4A mutants were independently cotransfected with the cap-dependent monocistronic luciferase reporter pCMV-Luc or the bicistronic luciferase reporter pJSS12 into Huh7 cells. To perform cap-dependent in-vitro-translation inhibition assay, GST and GST-NS4A fusion proteins that were recovered from the Sepharose 4B beads as described earlier were preincubated with 5 ll of rabbit reticulocyte lysate (RRL, Promega) at 4°C for 1 h. The results demonstrated that both NS4A and NS4B inhibited HCV IRES-mediated translation to levels similar to those of the cap-dependent translation, whereas no effect was detected with the viral NS3 protein (Figure 2d ). abstract: The genomic RNA of hepatitis C virus (HCV) encodes the viral polyprotein precursor that undergoes proteolytic cleavage into structural and nonstructural proteins by cellular and the viral NS3 and NS2-3 proteases. Nonstructural protein 4A (NS4A) is a cofactor of the NS3 serine protease and has been demonstrated to inhibit protein synthesis. In this study, GST pull-down assay was performed to examine potential cellular factors that interact with the NS4A protein and are involved in the pathogenesis of HCV. A trypsin digestion followed by LC-MS/MS analysis revealed that one of the GST-NS4A-interacting proteins to be eukaryotic elongation factor 1A (eEF1A). Both the N-terminal domain of NS4A from amino acid residues 1–20, and the central domain from residues 21–34 interacted with eEF1A, but the central domain was the key player involved in the NS4A-mediated translation inhibition. NS4A(21–34) diminished both cap-dependent and HCV IRES-mediated translation in a dose-dependent manner. The translation inhibitory effect of NS4A(21–34) was relieved by the addition of purified recombinant eEF1A in an in vitro translation system. Taken together, NS4A inhibits host and viral translation through interacting with eEF1A, implying a possible mechanism by which NS4A is involved in the pathogenesis and chronic infection of HCV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088589/ doi: 10.1007/s11373-006-9104-8 id: cord-269294-vx7xr80t author: Kwong, Ann D. title: Viral and cellular RNA helicases as antiviral targets date: 2005-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although there has been considerable progress in the development of antiviral agents in recent years, there is still a pressing need for new drugs both to improve on the properties of existing agents and to combat the problem of viral resistance. Helicases, both viral and human, have recently emerged as novel targets for the treatment of viral infections. Here, we discuss the role of these enzymes, factors affecting their potential as drug targets and progress in the development of agents that inhibit their activity using the hepatitis C virus-encoded helicase NS3 and the cellular helicase DDX3 adopted for use by HIV-1 as examples. url: https://www.ncbi.nlm.nih.gov/pubmed/16184083/ doi: 10.1038/nrd1853 id: cord-300642-c7adeis1 author: Lai, Andrew SH title: Viral nephropathy date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral infections can cause many glomerular diseases. The diagnostic criteria for virus-related nephropathy include detailed clinical and laboratory data, and tissue molecular analysis. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including tropism of the virus in the kidney, induction of abnormal immune complexes, direct cytopathogenic effects, and multiorgan failure. Hepatitis B virus is associated with membranous nephropathy and mesangiocapillary glomerulonephritis in endemic areas. Hepatitis C virus causes various forms of glomerulonephritis, including cryoglobulinemia-mediated glomerulonephritis. Infection with HIV is associated with a collapsing focal segmental glomerulosclerosis, a distinctive disease that affects mainly Africans and African Americans. In the course of HIV infection, other types of immune complex glomerulonephritis can occur, most frequently in whites. Recent reports indicate a role for parvovirus B19 in 'idiopathic' collapsing focal segmental glomerulosclerosis. Both hantaviruses, and coronaviruses associated with severe acute respiratory syndrome, can lead to acute renal failure. Renal biopsy followed by appropriate serological and molecular testing is essential for defining virus-related glomerular lesions and guiding prognostic and therapeutic evaluation. url: https://www.ncbi.nlm.nih.gov/pubmed/16932438/ doi: 10.1038/ncpneph0166 id: cord-307934-84zfabti author: Lai, Chao-Kuen title: Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date: 2014-06-06 words: 8211.0 sentences: 465.0 pages: flesch: 55.0 cache: ./cache/cord-307934-84zfabti.txt txt: ./txt/cord-307934-84zfabti.txt summary: Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. Both NS5A and Core proteins are found to be closely associated with and co-transported along the microtubules from the perinuclear region of cells via the LDs and endosomes to the plasma membrane. (A) The HCV-infected cells (at day 10 p.i.) were labeled with antibodies specific for Core protein (red) and NS5A (green) (upper row) or NS4B (green) (lower row). abstract: Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) serves dual functions in viral RNA replication and virus assembly. Here, we demonstrate that HCV replication complex along with NS5A and Core protein was transported to the lipid droplet (LD) through microtubules, and NS5A-Core complexes were then transported from LD through early-to-late endosomes to the plasma membrane via microtubules. Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Furthermore, exosomal markers CD63 and CD81 were also detected in the low-density fractions, but not in the high-density fractions. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. url: https://www.ncbi.nlm.nih.gov/pubmed/24905011/ doi: 10.1371/journal.pone.0099022 id: cord-305393-96mrxt8a author: Lai, Yvonne title: Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date: 2011-10-10 words: 9604.0 sentences: 587.0 pages: flesch: 60.0 cache: ./cache/cord-305393-96mrxt8a.txt txt: ./txt/cord-305393-96mrxt8a.txt summary: Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. Transfection of two plasmids, one containing an interferon stimulated response element (ISRE) promoter-driven firefly luciferase and a second encoding a constitutively expressed Renilla luciferase allow the analysis of TLR3 activation by different RNAs. HEK 293T cells expressing WT TLR3 responded to poly(I:C) (1-2 mg/ml), better than viral dsRNAs (1-2 mg/ml) purified from Reovirus and BPEV (Fig. 1B) . abstract: Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs) from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV) were also potent enhancers of TLR3 signaling by poly(I:C) or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. url: https://doi.org/10.1371/journal.pone.0025837 doi: 10.1371/journal.pone.0025837 id: cord-305085-bv7udg9k author: Lawrence, Robert M. title: Chapter 13 Transmission of Infectious Diseases Through Breast Milk and Breastfeeding date: 2011-12-31 words: 45849.0 sentences: 2358.0 pages: flesch: 45.0 cache: ./cache/cord-305085-bv7udg9k.txt txt: ./txt/cord-305085-bv7udg9k.txt summary: Postnatal exposure of susceptible infants to CMV, including premature infants without passively acquired maternal antibodies against CMV, infants born to CMV-seronegative mothers, and immunodeficient infants, can cause significant clinical illness (pneumonitis, hepatitis, thrombocytopenia).* In one study of premature infants followed up to 12 months, Vochem et al 430 found CMV transmission in 17 of 29 infants (59%) exposed to CMV virolactia and breastfed compared with no infants infected of 27 exposed to breast milk without CMV. 38, 104, 121 Laboratory reports demonstrate the presence of cell-free virus and cell-associated virus in breast milk as well as various immunologic factors that could block or limit infection.* A dose-response relationship has been observed, correlating the HIV viral load in human milk as well as a mother'' s plasma viral load with an increased transmission risk for the breastfed infant. 76 No case of transmission of yellow fever virus from an infected mother to her infant via breastfeeding or breast milk has been reported. abstract: nan url: https://api.elsevier.com/content/article/pii/B9781437707885100136 doi: 10.1016/b978-1-4377-0788-5.10013-6 id: cord-286334-d9v5xtx7 author: Li, Rui title: Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV date: 2020-04-30 words: 12955.0 sentences: 719.0 pages: flesch: 50.0 cache: ./cache/cord-286334-d9v5xtx7.txt txt: ./txt/cord-286334-d9v5xtx7.txt summary: More detailed monitoring on how these physiological parameters change over time (perhaps including more complex cytokine studies), in these severely ill, influenza A(H1N1)pdm09-infected patients admitted to ICU-ECMO units, may eventually yield data to improve their management and clinical outcomes. 5 In the current study, we characterized a new HCV subtypes among chronic hepatitis C patients in Yunnan, China, initially designated as 6xi, further analyzed its evolutionary history and investigated its baseline RAS by next generation sequencing (NGS) method. The samples met the following inclusion criteria: (1) hepatitis C antibody-positive for 6 months with normal serum alanine aminotransferase (ALT) levels; (2) subject was residing in Yunnan province and was over 18 years old; (3) complete demographic information and clinical data were available; (4) consented to the use of patient information in studies on HCV epidemics; and (5) were treatment-naïve during sampling. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32092392/ doi: 10.1016/j.jinf.2020.02.013 id: cord-260099-mthwab4p author: Li, Yi title: C-type lectin LSECtin interacts with DC-SIGNR and is involved in hepatitis C virus binding date: 2009-02-21 words: 3479.0 sentences: 195.0 pages: flesch: 59.0 cache: ./cache/cord-260099-mthwab4p.txt txt: ./txt/cord-260099-mthwab4p.txt summary: The present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells. About a half of the DC-SIGNR-HEK293T cells were bound to the soluble Fc-LSECtin but not control-Fc protein, whereas only 6% of the mock cells were adhered to LSECtin (Fig. 1c) . Pre-incubation with the soluble LSECtin protein resulted in a dramatic decrease in the affinity of HCV E2 to the HEK293T-LSECtin cells (Fig. 3c) . Our present study suggests that LSECtin, a recently identified C-type lectin, could interact with DC-SIGNR and CD81 and was involved in HCV binding. previously reported that they could not detect the binding of HCV pseudotype particles to LSECtin expressed cells [14] , which is inconsistent with our results. In summary, the present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells. abstract: Hepatitis C virus (HCV) is a major cause of liver disease. However, the detailed mechanism underlying hepatocyte infection with HCV is not yet completely understood. We previously identified a novel C-type lectin—LSECtin predominantly expressed on liver sinusoidal endothelial cells. Here we demonstrate that LSECtin can interact with two HCV receptors, DC-SIGNR and CD81, through its central ectodomain. Furthermore, cells expressing LSECtin specifically can be attached by the naturally occurring HCV in the sera of infected individuals. This binding was found to be mediated by the HCV E2 glycoprotein and could be efficiently inhibited by EGTA but not by mannan treatment. The present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11010-009-0056-y) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s11010-009-0056-y doi: 10.1007/s11010-009-0056-y id: cord-280330-ibvbowl0 author: Lin, Liang-Tzung title: Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry date: 2013-08-07 words: 7359.0 sentences: 351.0 pages: flesch: 45.0 cache: ./cache/cord-280330-ibvbowl0.txt txt: ./txt/cord-280330-ibvbowl0.txt summary: While vaccine efforts have proven successful for preventing and eradicating some viral infections, many viruses cannot be targeted by immunization, including dengue virus (DENV), human cytomegalovirus (HCMV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV) [1] [2] [3] [4] [5] . We demonstrated that the two structurally-related compounds mediated their antiviral activities by targeting HSV-1 viral glycoproteins that interact with cell surface GAGs. Taking note of the fact that many viruses employ GAGs to initially bind to the host cell, and based on evidence that CHLA and PUG may act as GAG-competitors, we explored the antiviralpotential of these two tannins against a number of viruses known to interact with GAGs. Viral models included DENV, HCMV, HCV, MV, and RSV ( Table 1 ). We suggest that CHLA and PUG have potential as novel cost-effective and broad-spectrum antivirals for controlling emerging/recurring infections by viruses that engage host cell surface GAGs. Dulbecco''s modified Eagle''s medium (DMEM) and alpha minimal essential medium (AMEM) were purchased from GIBCO-Invitrogen (Carlsbad, CA, USA). abstract: BACKGROUND: We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. RESULTS: Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. CONCLUSIONS: CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified. url: https://doi.org/10.1186/1471-2180-13-187 doi: 10.1186/1471-2180-13-187 id: cord-342901-ca2xxkb2 author: Lloyd, Richard E. title: Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses date: 2015-05-31 words: 16221.0 sentences: 823.0 pages: flesch: 50.0 cache: ./cache/cord-342901-ca2xxkb2.txt txt: ./txt/cord-342901-ca2xxkb2.txt summary: Though PTB was the first, a wide spectrum of factors, largely nuclear RBPs, have also been proposed as poliovirus ITAFs, including Lupus autoantigen (La) (Meerovitch et al., 1993 (Meerovitch et al., , 1989 , poly(rC)binding proteins (PCBPs) (Blyn et al., 1996; Gamarnik and Andino, 1997) , upstream of N-ras (UNR) (Anderson et al., 2007; Boussadia et al., 2003; Hunt et al., 1999) , SRp20 (Bedard et al., 2007) and glycyl-tRNA synthetase (GARS) (Andreev et al., 2012) (Table 1 ). In addition, certain ITAFs play crucial roles in regulating the conversion of translation-competent genomic RNAs into replicationcompetent RNAs. PTB was known as a nuclear splicing factor when its role as an ITAF of poliovirus and EMCV was discovered; a classic hijacked nuclear protein pressed into a new role required for the virus. abstract: Abstract Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups. url: https://www.ncbi.nlm.nih.gov/pubmed/25818028/ doi: 10.1016/j.virol.2015.03.001 id: cord-307817-2vy28i4m author: Lou, Zhiyong title: Current progress in antiviral strategies date: 2014-01-14 words: 7555.0 sentences: 343.0 pages: flesch: 36.0 cache: ./cache/cord-307817-2vy28i4m.txt txt: ./txt/cord-307817-2vy28i4m.txt summary: The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Based on the complex structure of the PA C-terminal domain (PA C ) and the first 25 amino acids of PB1 [99] , a subset of modifications on N-terminal peptide of PB1 was shown to diminish the binding affinity of PA and PB1, inhibit polymerase activity, and attenuate the replication of influenza virus [100] [101] [102] . Because both the polymerase complex and NP show significant conservation between different influenza viruses, these results demonstrated that targeting the formation of viral RNP is a valid approach to the development of small molecule therapies against serious antiviral resistance to currently available drugs, such as adamantanes or neuraminidase inhibitors. abstract: The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. Virus-targeting antivirals can function directly or indirectly to inhibit the biological functions of viral proteins, mostly enzymatic activities, or to block viral replication machinery. Host-targeting antivirals target the host proteins that are involved in the viral life cycle, regulating the function of the immune system or other cellular processes in host cells. Here we review key targets and considerations for the development of both antiviral strategies. url: https://www.sciencedirect.com/science/article/pii/S0165614713002265 doi: 10.1016/j.tips.2013.11.006 id: cord-024003-698d15gk author: Loutfy, Samah A title: Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines date: 2020-04-22 words: 6596.0 sentences: 316.0 pages: flesch: 49.0 cache: ./cache/cord-024003-698d15gk.txt txt: ./txt/cord-024003-698d15gk.txt summary: This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. 17, 19 Previously, chitosan nanoparticles (CsNPs) have been conjugated with antiretroviral agents like saquinavir, a protease inhibitor, to improve anti-HIV therapy; cell targeting efficiency increased by 92% compared to the soluble drug control. Antiviral activities of curcumin, CsNPs and CuCs nanocomposite were tested against the viral entry in infected Huh7 cells from positive HCV-4a patients through mixing of equal volumes of the nontoxic concentrations of the investigated materials and viral titer; in this assay one viral titer was involved (10 5 IU/mL). The HCV core protein expression level post-treatment of HCV infected Huh7 cells with curcumin, CsNPs, and CuCs nanocomposite against viral replication and entry was quantified in relation to β-actin as a control ( Table 7 , Figure 8 ). abstract: PURPOSE: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. METHODS: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. RESULTS: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29–39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes’ expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. CONCLUSION: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184126/ doi: 10.2147/ijn.s241702 id: cord-314753-xflhxb13 author: Manso, Carmen F. title: Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date: 2017-06-23 words: 6333.0 sentences: 296.0 pages: flesch: 48.0 cache: ./cache/cord-314753-xflhxb13.txt txt: ./txt/cord-314753-xflhxb13.txt summary: The percentage of reads mapping to RNA virus genomes in the rRNA-depleted BBV Panel samples was between 40 and 150-fold higher than in corresponding untreated controls. The depth plots in Fig. 3 again show unbiased and even coverages across both genomes, and the percentages of reads mapping to viral targets was again much higher in the rRNA-depleted sample than in the untreated comparator (61-fold and 85-fold for HCV and HPgV respectively). By depleting host-derived nucleic acids and making modifications to an existing library preparation protocol to account for ultra-low RNA input quantities, we have been able to reconstruct effectively full-length genomes of HCV, HEV and HIV from plasma samples with viral loads of 10 4 IU/ml (copies/ml for HIV) and substantial fractions of complete genomes at 10 3 IU/ml. Additionally, our system was able to recover viral sequences from a panel of diverse RNA viruses diluted in human plasma, with a broad correlation between the genomic coverage and depth metrics and approximate concentration. abstract: RNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses – HIV, HCV and HEV. We recovered complete genomes and up to 43% of the genome from samples with viral loads of 10(4) and 10(3) IU/ml respectively. Additionally, we demonstrated the utility of this method in detecting and characterising members of diverse RNA virus families within a human plasma background, some present at very low levels. By applying this method to a patient sample series, we have simultaneously determined the full genome of both a novel subtype of HCV genotype 6, and a co-infecting human pegivirus. This method builds upon earlier RNA metagenomic techniques and can play an important role in the surveillance and diagnostics of blood-borne viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/28646219/ doi: 10.1038/s41598-017-02239-5 id: cord-001421-6t5puo6p author: Marfà, Santiago title: Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date: 2014-10-02 words: 5057.0 sentences: 229.0 pages: flesch: 46.0 cache: ./cache/cord-001421-6t5puo6p.txt txt: ./txt/cord-001421-6t5puo6p.txt summary: The serum proteomic profile and routine liver and renal function tests were initially analyzed in a training set of 10 HCV-RNA recurrent LT patients 6 months post LT that showed a fibrosis stage F$1 at 1 year after LT. HVPG was assessed in 53 of these patients and the average value was of 5.560.8 mm Hg. All the serum samples showed a quite similar expression pattern and coincidences included both the different peptide fragments detected and the signal intensity of these fragments (Data S4). All serum samples included in the test set showed an intensity m/z 5905 peak well below the values found in both healthy subjects and non recurrent HCV patients. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. abstract: Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183580/ doi: 10.1371/journal.pone.0109254 id: cord-347992-coby2m6e author: Marton, Soledad title: In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date: 2010-06-28 words: 10035.0 sentences: 535.0 pages: flesch: 45.0 cache: ./cache/cord-347992-coby2m6e.txt txt: ./txt/cord-347992-coby2m6e.txt summary: Although ribozymes and DNAzymes have been extensively assayed as potential therapeutic agents, and different clinical trials have already tested their efficiency against various diseases [49] [50] [51] [52] , very few reports have described the direct application of in vitro selection strategies in the development of potentially therapeutic catalytic nucleic acids. Molecular studies have shown that this aptamer binds to the cell surface protein nucleolin and inhibits the activity of NF-KB, a ubiquitous transcription factor, through intracellular complex formation [108] . In a different approach, SELEX has been performed with the E2F1 protein to find in vitro selected RNA aptamers that bind to and inhibit E2F activity. Astier-Gi''s group described the characterization of two DNA aptamers (27v and 127v) that specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B), inhibiting its activity in vitro [146] . In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins abstract: It was only relatively recently discovered that nucleic acids participate in a variety of biological functions, besides the storage and transmission of genetic information. Quite apart from the nucleotide sequence, it is now clear that the structure of a nucleic acid plays an essential role in its functionality, enabling catalysis and specific binding reactions. In vitro selection and evolution strategies have been extremely useful in the analysis of functional RNA and DNA molecules, helping to expand our knowledge of their functional repertoire and to identify and optimize DNA and RNA molecules with potential therapeutic and diagnostic applications. The great progress made in this field has prompted the development of ex vivo methods for selecting functional nucleic acids in the cellular environment. This review summarizes the most important and most recent applications of in vitro and ex vivo selection strategies aimed at exploring the therapeutic potential of nucleic acids. url: https://www.ncbi.nlm.nih.gov/pubmed/20657381/ doi: 10.3390/molecules15074610 id: cord-017764-h1w9gbxk author: Meanwell, Nicholas A. title: The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex date: 2018-06-08 words: 9250.0 sentences: 389.0 pages: flesch: 39.0 cache: ./cache/cord-017764-h1w9gbxk.txt txt: ./txt/cord-017764-h1w9gbxk.txt summary: A groundbreaking clinical trial that combined daclatasvir (1) with the protease inhibitor asunaprevir (52) established that a chronic HCV infection could be cured with small molecule therapy in the absence of immune stimulation, setting the stage for approval of this regimen for the treatment of GT-1b-infected subjects by the Japanese health authorities on July 4, 2014. The discovery of the hepatitis C virus (HCV) nonstructural 5A (NS5A) replication complex inhibitor daclatasvir (1) began with the development of a genotype 1b (GT-1b) replicon that was implemented as a phenotypic screen using a design that conferred a stringent triaging of hit molecules [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] . A screen of compounds selected from the library of HCV NS5A inhibitors assessed in the presence of 1 using the Tyr93Asn GT-1aresistant replicon, followed by SAR optimization, identified Syn-395 (52) as a molecule capable of restoring the sensitivity of resistant virus to the inhibitory effects of 1. Discovery of daclatasvir, a pan-genotypic hepatitis C virus NS5A replication complex inhibitor with potent clinical effect abstract: The discovery of the hepatitis C virus (HCV) NS5A replication inhibitor daclatasvir (1) had its origins in a phenotypic screening lead. However, during the optimization campaign, it was observed that some members of the chemotype underwent a radical dimerization under the assay conditions. This redirected the effort to focus on palindromic molecules, a species subsequently shown to complement the dimeric nature of the NS5A protein. The most challenging aspect of the discovery program was extending antiviral activity to encompass GT-1a virus which was accomplished only after the development of extensive structure-activity relationships. In clinical trials, oral administration of daclatasvir (1) produced a profound effect on viral load with onset that was more rapid than had been seen previously with either NS3 protease or NS5B polymerase inhibitors. A groundbreaking clinical trial that combined daclatasvir (1) with the protease inhibitor asunaprevir (52) established that a chronic HCV infection could be cured with small molecule therapy in the absence of immune stimulation, setting the stage for approval of this regimen for the treatment of GT-1b-infected subjects by the Japanese health authorities on July 4, 2014. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122418/ doi: 10.1007/7355_2018_47 id: cord-293646-d4qcckh1 author: Meanwell, Nicholas A. title: Chapter 22. Non-HIV antiviral agents date: 2003-12-31 words: 4178.0 sentences: 198.0 pages: flesch: 46.0 cache: ./cache/cord-293646-d4qcckh1.txt txt: ./txt/cord-293646-d4qcckh1.txt summary: The first small molecule inhibitor of Hepatitis C Virus (HCV), the NS3 protease inhibitor BILN-2061, entered phase 2 clinical trials, producing a striking reduction in viral load in treated individuals. Inhibitors of Hepatitis B Virus (HBV) -Adefovir dipivoxil iHepsera''") (1) was approved in the US for the treatment of HBV on September 20'', 2002 and in the European Union on March 1 lth, 2003, providing a second small molecule antiviral to add to lamivudine (3TC) and the injectable protein IFNa as the only approved agents for treating HBV infection. Pyridinedicarboxamide S represents the first report of a non-nucleoside inhibitor of HBV reverse transcriptase enantiomer of q is active in cell culture and appears to prevent proper formation of the viral nucleocapsrd. A significant advance towards establishing a correlation between replicon inhibition and clinical efficacy was recently accomplished with the disclosure of preliminary clinical data for BILN-2061, a selective inhibitor of the NS3 serine protease of HCV that is structurally related to 13. abstract: Publisher Summary This chapter focuses on non-HIV antiviral agents. The development of antiviral agents to treat non-HIV infections is largely focused on therapies for the treatment of chronic hepatitis infections B and C. Nucleoside analog continue to be the mainstay of Hepatitis B Virus (HBV) therapeutics. The first small molecule inhibitor of Hepatitis C Virus (HCV), the NS3 protease inhibitor BILN-2061, entered phase 2 clinical trials, producing a striking reduction in viral load in treated individuals. The development of the HCV replicon system and its application to screening for antiviral agents provided tangible benefit with the disclosure of mechanistically and structurally diverse HCV inhibitors. Adefovir dipivoxil has been approved in the United States and the European Union for the treatment of HBV, providing a second small molecule antiviral to add to lamivudine (3TC) and the injectable protein IFNα as the only approved agents for treating HBV infection. The chapter also provides details of the inhibitors of hepatitis B and C virus, the inhibitors of simplex virus and human cytomegalovirus, the inhibitors of respiratory viruses and the inhibitors of West Nile virus and Papilloma virus. url: https://www.sciencedirect.com/science/article/pii/S0065774303380236 doi: 10.1016/s0065-7743(03)38023-6 id: cord-350640-sz6xj5o3 author: Menzel, Nicolas title: MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles date: 2012-07-26 words: 10059.0 sentences: 549.0 pages: flesch: 49.0 cache: ./cache/cord-350640-sz6xj5o3.txt txt: ./txt/cord-350640-sz6xj5o3.txt summary: When transfecting our infectious firefly luciferase reporter virus genome Luc-Jc1 [14] into highly permissive Huh-7.5 human hepatoma cells [15] cultured in the presence or absence of serum, we measured comparable levels of luciferase activity 4 to 48 h after transfection ( Figure S1A ). Among the inhibitors tested, U0126 a selective inhibitor of the MAPK/ERK pathway, substantially decreased the production of infectious virus particles as is evident from the dose-dependent reduction of luciferase activity in the inoculated cells ( Figure 1B) . To investigate if PLA2G4A activity is relevant for the production of infectious HCV particles we treated Luc-Jc1 transfected cells with pyrrolidine-2 (Py-2), a specific inhibitor of this type of phospholipase [22, 23] . Irrespective of culturing these cells in the presence or absence of serum, we observed a strong and dose-dependent inhibition of production of infectious particles resulting in a more than 100-fold reduction of luciferase transduction at 5 and 20 mM of Py-2, respectively ( Figure 2B ). abstract: Hepatitis C virus (HCV) has infected around 160 million individuals. Current therapies have limited efficacy and are fraught with side effects. To identify cellular HCV dependency factors, possible therapeutic targets, we manipulated signaling cascades with pathway-specific inhibitors. Using this approach we identified the MAPK/ERK regulated, cytosolic, calcium-dependent, group IVA phospholipase A2 (PLA2G4A) as a novel HCV dependency factor. Inhibition of PLA2G4A activity reduced core protein abundance at lipid droplets, core envelopment and secretion of particles. Moreover, released particles displayed aberrant protein composition and were 100-fold less infectious. Exogenous addition of arachidonic acid, the cleavage product of PLA2G4A-catalyzed lipolysis, but not other related poly-unsaturated fatty acids restored infectivity. Strikingly, production of infectious Dengue virus, a relative of HCV, was also dependent on PLA2G4A. These results highlight previously unrecognized parallels in the assembly pathways of these human pathogens, and define PLA2G4A-dependent lipolysis as crucial prerequisite for production of highly infectious viral progeny. url: https://www.ncbi.nlm.nih.gov/pubmed/22911431/ doi: 10.1371/journal.ppat.1002829 id: cord-332747-u46xryoo author: Mingorance, Lidia title: Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation date: 2018-09-18 words: 10355.0 sentences: 485.0 pages: flesch: 37.0 cache: ./cache/cord-332747-u46xryoo.txt txt: ./txt/cord-332747-u46xryoo.txt summary: To determine which aspects of the HCV replication cycle are limited by lipin1 silencing, single cycle infection experiments were conducted by inoculating control and lipin1-deficient cell cultures at MOI 10 with genotype 2a D183 virus. Once cultures reached >95% of HCV-positive cells, they were transduced with lentiviral vectors expressing control, HCV RNA-targeting or LPIN1-specific shRNAs. At day 7 post-transduction, cells were split and samples of the cells and supernatants were collected 24 hours later to determine infectious virus production rate by infectivity titration HCV (C) and RNA levels by RT-qPCR (D). This reduced abundance is illustrated by a significant reduction in the fraction of cells displaying vesicular structures in lipin1-deficient cell cultures (Fig 7H) despite comparable transfection efficiency and viral protein expression levels, indicating that lipin1 may be required in a critical step leading to formation of the HCV-induced vesicular compartment. abstract: Hepatitis C virus (HCV) infection constitutes a significant health burden worldwide, because it is a major etiologic agent of chronic liver disease, cirrhosis and hepatocellular carcinoma. HCV replication cycle is closely tied to lipid metabolism and infection by this virus causes profound changes in host lipid homeostasis. We focused our attention on a phosphatidate phosphate (PAP) enzyme family (the lipin family), which mediate the conversion of phosphatidate to diacylglycerol in the cytoplasm, playing a key role in triglyceride biosynthesis and in phospholipid homeostasis. Lipins may also translocate to the nucleus to act as transcriptional regulators of genes involved in lipid metabolism. The best-characterized member of this family is lipin1, which cooperates with lipin2 to maintain glycerophospholipid homeostasis in the liver. Lipin1-deficient cell lines were generated by RNAi to study the role of this protein in different steps of HCV replication cycle. Using surrogate models that recapitulate different aspects of HCV infection, we concluded that lipin1 is rate limiting for the generation of functional replicase complexes, in a step downstream primary translation that leads to early HCV RNA replication. Infection studies in lipin1-deficient cells overexpressing wild type or phosphatase-defective lipin1 proteins suggest that lipin1 phosphatase activity is required to support HCV infection. Finally, ultrastructural and biochemical analyses in replication-independent models suggest that lipin1 may facilitate the generation of the membranous compartment that contains functional HCV replicase complexes. url: https://www.ncbi.nlm.nih.gov/pubmed/30226904/ doi: 10.1371/journal.ppat.1007284 id: cord-284904-qw1ig2v4 author: Mizui, Tomokazu title: Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy date: 2009-09-17 words: 4099.0 sentences: 250.0 pages: flesch: 49.0 cache: ./cache/cord-284904-qw1ig2v4.txt txt: ./txt/cord-284904-qw1ig2v4.txt summary: In this study, we investigated the role of autophagy on hepatitis C virus (HCV) RNA replication and demonstrated anti-HCV effects of an autophagic proteolysis inhibitor, chloroquine. Inhibition of autophagy and replication of HCV replicon Cells were treated with 3-methyladenine (10 mM) or mixture of E64d (1 lg/ml) and pepstatin A (1 lg/ml), chloroquine (10 -7 -10 -3 M), interferon (IFN)a (100 U/ml) for 18 h, the levels of replication of HCV replicon were assessed by luciferase assay. To clarify the role of autophagy on the replication of HCV, Huh7/ Rep-Feo cells were treated with 3-methyladenine (10 mM) or a mixture of E64d (10 lg/ml) and pepstatin A (10 lg/ml) which inhibited autophagic protein degradation. Anti-HCV effect of chloroquine independent of IFN signaling pathway IFN-inducible double-stranded RNA-activated protein kinase R (PKR) plays a key antiviral role against hepatitis C virus [26, 27] . abstract: BACKGROUND: Autophagy has been reported to play a pivotal role on the replication of various RNA viruses. In this study, we investigated the role of autophagy on hepatitis C virus (HCV) RNA replication and demonstrated anti-HCV effects of an autophagic proteolysis inhibitor, chloroquine. METHODS: Induction of autophagy was evaluated following the transfection of HCV replicon to Huh-7 cells. Next, we investigated the replication of HCV subgenomic replicon in response to treatment with lysosomal protease inhibitors or pharmacological autophagy inhibitor. The effect on HCV replication was analyzed after transfection with siRNA of ATG5, ATG7 and light-chain (LC)-3 to replicon cells. The antiviral effect of chloroquine and/or interferon-α (IFNα) was evaluated. RESULTS: The transfection of HCV replicon increased the number of autophagosomes to about twofold over untransfected cells. Pharmacological inhibition of autophagic proteolysis significantly suppressed expression level of HCV replicon. Silencing of autophagy-related genes by siRNA transfection significantly blunted the replication of HCV replicon. Treatment of replicon cells with chloroquine suppressed the replication of the HCV replicon in a dose-dependent manner. Furthermore, combination treatment of chloroquine to IFNα enhanced the antiviral effect of IFNα and prevented re-propagation of HCV replicon. Protein kinase R was activated in cells treated with IFNα but not with chloroquine. Incubation with chloroquine decreased degradation of long-lived protein leucine. CONCLUSION: The results of this study suggest that the replication of HCV replicon utilizes machinery involving cellular autophagic proteolysis. The therapy targeted to autophagic proteolysis by using chloroquine may provide a new therapeutic option against chronic hepatitis C. url: https://doi.org/10.1007/s00535-009-0132-9 doi: 10.1007/s00535-009-0132-9 id: cord-264936-3posyr5n author: Mohammadzadeh, Sara title: Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications date: 2014-11-24 words: 6202.0 sentences: 292.0 pages: flesch: 49.0 cache: ./cache/cord-264936-3posyr5n.txt txt: ./txt/cord-264936-3posyr5n.txt summary: RESULTS: The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of "GGTAAG" splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). In this study, we aimed to: i) Construct an efficient transient tobacco expression system for HCVcp N-121 by designing a highly codon-optimized gene and employment of the Iranian Jafarabadi-tobacco plant cultivar which is a high biomass producer ii) Evaluate the expression level of HCVcp for a potato virus X-based vector (PVX) (32) com-pared to a classic pBI121 binary plant vector in co-agroinfiltration with P19 gene silencing suppressor plasmid and iii) Assess the antigenicity of this tobacco-derived HCVcp for potential clinical (diagnostic and vaccine formulation) applications. abstract: BACKGROUND: Hepatitis C virus (HCV) is major cause of liver cirrhosis in humans. HCV capsid (core) protein (HCVcp) is a highly demanded antigen for various diagnostic, immunization and pathogenesis studies. Plants are considered as an expression system for producing safe and inexpensive biopharmaceutical proteins. Although invention of transgenic (stable) tobacco plants expressing HCVcp with proper antigenic properties was recently reported, no data for “transient-expression” that is currently the method of choice for rapid, simple and lower-priced protein expression in plants is available for HCVcp. OBJECTIVES: The purpose of this study was to design a highly codon-optimized HCVcp gene for construction of an efficient transient-plant expression system for production of HCVcp with proper antigenic properties in a regional tobacco plant (Iranian Jafarabadi-cultivar) by evaluation of different classes of vectors and suppression of gene-silencing in tobacco. MATERIALS AND METHODS: A codon-optimized gene encoding the Kozak sequence, 6xHis-tag, HCVcp (1-122) and KDEL peptide in tandem (from N- to C-terminal) was designed and inserted into potato virus-X (PVX) and classic pBI121 binary vectors in separate cloning reactions. The resulted recombinant plasmids were transferred into Agrobacterium tumefaciens and vacuum infiltrated into tobacco leaves. The effect of gene silencing suppressor P19 protein derived from tomato bushy stunt virus on the expression yield of HCVcp by each construct was also evaluated by co-infiltration in separate groups. The expressed HCVcp was evaluated by dot and western blotting and ELISA assays. RESULTS: The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of “GGTAAG” splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). The plant-derived HCVcp (pHCVcp) could properly identify the HCVcp antibody in HCV-infected human sera compared to Escherichia coli-derived HCVcp (eHCVcp), indicating its potential for diagnostic/immunization applications. CONCLUSIONS: By employment of gene optimization strategies, use of viral-based vectors and suppression of plant-derived gene silencing effect, efficient transient expression of HCVcp in tobacco with proper antigenic properties could be possible. url: https://doi.org/10.5812/hepatmon.20524 doi: 10.5812/hepatmon.20524 id: cord-030361-0tepkjdl author: Mohammed Abdul, Mubeen Khan title: Hepatitis C Virus in the Elderly in the Direct-Acting Antiviral Era: from Diagnosis to Cure date: 2020-08-11 words: 4991.0 sentences: 233.0 pages: flesch: 42.0 cache: ./cache/cord-030361-0tepkjdl.txt txt: ./txt/cord-030361-0tepkjdl.txt summary: In a study conducted by Foster and colleagues, data was combined from nine phase 2 and phase 3 clinical trials to evaluate efficacy and safety outcomes in HCV patients ≥ 65 years old treated with the pan-genotypic regimen, glecaprevir/pibrentasvir, for 8, 12, or 16 weeks [28] . Shiffman and colleagues reported outcomes of 123 patients aged 65 years or older enrolled in three phase 3 studies who received sofosbuvir/velpatasvir, a pan-genotypic DAA, for 12 weeks for the treatment of chronic HCV [29] . Safety and efficacy of sofosbuvir/ velpatasvir for the treatment of chronic hepatitis C in patients aged 65 years or older: a retrospective analysis of phase 3 studies The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection abstract: PURPOSE OF REVIEW: Hepatitis C (HCV) is the most common cause of viral hepatitis in elderly individuals. This patient population previously experienced suboptimal outcomes with interferon-based regimens. Unfortunately, patients aged 65 years and older were underrepresented in phase 2 and 3 clinical trials with newer direct acting antiviral (DAA) therapies. Since the advent of second-generation DAA in 2013, numerous robust real-world experiences highlighting the efficacy and safety of DAA in the elderly have been published. This review article summarizes the cascade of care for hepatitis C from diagnosis to cure from an evidence-based perspective of the aging population. RECENT FINDING: In a large study from the Veterans Affairs Healthcare System, the overall sustained virologic response (SVR) of 15,884 patients treated with DAA regimens was 91.2%. These newer therapies remained highly effective in the subset of patients aged 65 years and older with SVR rates above 90%. A Spanish National Registry reported outcomes in patients ≥ 65 years old treated for HCV with oral DAA regimens over a 2-year period. The overall SVR was 94% in the study of 1252 subjects. SUMMARY: Current real-world data imply DAA treatment regimens remain highly effective and safe in elderly patients when compared to the general population. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418288/ doi: 10.1007/s40506-020-00231-8 id: cord-350600-73q8mve4 author: Myint, S. title: Detection of human coronavirus 229E in nasal washings using RNA:RNA hybridization date: 2005-12-09 words: 1996.0 sentences: 126.0 pages: flesch: 61.0 cache: ./cache/cord-350600-73q8mve4.txt txt: ./txt/cord-350600-73q8mve4.txt summary: A method is described for the detection of human coronavirus 229E (HCV 229E) in nasal washings using RNA:RNA filter hybridization. In this paper we describe a specific and sensitive test to detect one of these major groups, HCV 2293, in nasal washings. Briefly, using a method based on that of Gubler and Hoffmann [19831, cDNAs were generated from HCV 2293 RNA isolated from infected C16 cells [Phillpotts, 19831. The results of virus titration and probing of nasal washings from seven volunteers are presented in Table I . Three of the seven volunteers suffered a cold, and all three volunteers had detectable coronavirus RNA in their nasal washings. The results we have obtained show that the detection of HCV 2293 infection by nucleic acid hybridisation is a reliable and specific method. Hybridisation to known quantities of HCV 2293 RNA showed that less than 1 ng of virus-specific RNA from C16 cells infected with HCV 2293 could be detected. abstract: A method is described for the detection of human coronavirus 229E (HCV 229E) in nasal washings using RNA:RNA filter hybridization. Volunteers were inoculated with HCV 229E, and daily nasal washings were collected. These washings were then examined for the presence of viral RNA using a single‐stranded RNA probe. Nucleic acid hybridization is shown to be a sensitive technique for the diagnosis of HCV 229E infections. url: https://www.ncbi.nlm.nih.gov/pubmed/2584959/ doi: 10.1002/jmv.1890290113 id: cord-018785-tcr5xlf8 author: Nambiar, Puja title: Infection in Kidney Transplantation date: 2018-06-27 words: 9364.0 sentences: 506.0 pages: flesch: 36.0 cache: ./cache/cord-018785-tcr5xlf8.txt txt: ./txt/cord-018785-tcr5xlf8.txt summary: The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. The risk factors for development of CMV disease include donor seropositivity/recipient seronegativity(Dþ/RÀ), use of induction immunosuppression (antilymphocyte antibodies), donor age >60 years, simultaneous kidney-pancreas transplantation, treatment for acute rejection, impaired transplant function, and concurrent infection from other viruses (like EBV and HHV-6 and 7) (De Keyzer et al. The risk factors for PTLD include EBV naïve recipients who receive EBV seropositive organs, active primary EBV infection, younger recipient, coinfection by CMV and other viruses, prior splenectomy, second transplant, acute or chronic graft versus host disease, immunosuppressive drug regimen (OKT3 or polyclonal antilymphocyte antibody), and the type of organ transplanted. abstract: Infection is an important cause of morbidity and mortality after kidney transplantation. It has been estimated that 70% of kidney transplant recipients will experience an infection episode within the first 3 years after transplantation (Dharnidharka et al. 2007). After cardiovascular disease, infection is the second leading cause of death in recipients with allograft function (Snyder et al. 2009). The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. Pretransplant screening, immunizations, and optimal antibacterial and antiviral prophylaxis can help to reduce the impact of infection. Awareness of the approach to infection in the transplant recipient including diagnostic and management strategies is essential to optimizing outcomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123753/ doi: 10.1007/978-3-319-19617-6_22 id: cord-013176-6ckuya1w author: Ninfali, Paolino title: Antiviral Properties of Flavonoids and Delivery Strategies date: 2020-08-21 words: 8102.0 sentences: 372.0 pages: flesch: 35.0 cache: ./cache/cord-013176-6ckuya1w.txt txt: ./txt/cord-013176-6ckuya1w.txt summary: Quercetin, extracted from Embelia ribes (Mirsinaceae), exhibited antiviral effects against HCV, exerted through activity inhibition of the viral protease Non-Structural protein 3 (NS3), leading to a decrease in HCV replication [36] . The natural extract of Tetrastigma hemsleyanum (Vitaceae) contains many flavonoids, including vitexin, vitexin-2-O-rhamnoside, isorhamnetin, rutin, kaempferol, astragalin, quercitrin, quercetin and iso-quercetin, which were shown to be able to exert anti-influenza virus activity, with different efficiency, through the reduction of the number of plaques induced by the influenza virus in infected Madin-Darby Canine Kidney (MDCK) cells [21] . In future perspective, this approach could be considered in order to possibly improve the antiviral activity of some flavonoids, like baicalin, that was able, like fludarabine [65] , to act against HIV-1 chronic infection of human monocytes and macrophages, inhibiting the fusion of HIV virus envelope proteins with these cells [73] . abstract: This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551920/ doi: 10.3390/nu12092534 id: cord-001848-idmj2d7p author: Onabajo, Olusegun O. title: Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date: 2015-11-01 words: 7203.0 sentences: 335.0 pages: flesch: 47.0 cache: ./cache/cord-001848-idmj2d7p.txt txt: ./txt/cord-001848-idmj2d7p.txt summary: We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Previously, we showed that transient transfection of an expression construct that generates IFN-l4 protein induced interferon signaling, with activation of interferon-stimulated genes (ISGs) and generation of antiviral response in HepG2, a human hepatoma cell line (Prokunina-Olsson and others 2013). The stable HepG2-ISRE-Luc cells were transfected with corresponding constructs in 96-well plates; untransfected cells were treated with human recombinant interferons-IFNa (2 ng/mL; PBL Assay Science) or custom IFN-l3 (10 ng/ mL). Previously, by performing Western blot analysis, we were unable to detect IFN-l4 in culture media of HepG2 cells transiently transfected with an IFN-l4-producing construct, even though this transfection resulted in strong activation of interferon signaling (Prokunina-Olsson and others 2013). IFN-l4 was detectable in culture media of IFNL4-transfected PHHs and HepG2 cells, but not in corresponding Halo-transfected cells (Fig. 2B) . abstract: Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be generated only in individuals carrying a ΔG frame-shift allele of an exonic genetic variant (rs368234815-ΔG/TT). The rs368234815-ΔG allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection. Here, we further explored the biological function of IFN-λ4 expressed in human hepatic cells—a hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs). We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Not only did we observe significant intracellular retention of IFN-λ4 but also detected secreted IFN-λ4 in the culture media of expressing cells. Secreted IFN-λ4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-λ4-expressing and surrounding cells in transwell assays. Specifically, in PHHs, secreted IFN-λ4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10. In IFN-λ4-expressing HepG2 cells, we also observed decreased proliferation and increased cell death. All IFN-λ4-induced phenotypes—activation of ISGs, decreased proliferation, and increased cell death—could be inhibited by an anti-IFN-λ4-specific antibody. Our study offers new insights into biology of IFN-λ4 and its possible role in HCV clearance. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642834/ doi: 10.1089/jir.2014.0161 id: cord-022380-49oti4zg author: Panlilio, Adelisa L title: Occupational Infectious Diseases date: 2009-05-15 words: 15592.0 sentences: 809.0 pages: flesch: 41.0 cache: ./cache/cord-022380-49oti4zg.txt txt: ./txt/cord-022380-49oti4zg.txt summary: Because infectious diseases may represent the most common cause of time lost from work, it is important for the clinician concerned with occupational medicine to understand the relationship of specific infections to specific work environments and practices, and to give at least as much attention to prevention as to diagnosis and treatment. Susceptible household contacts of infected adults and children pose a transmission risk in the workplace during the period of virus shedding, beginning about 10 days before the development of rash (about 1 week after exposure) until 7 days after rash appears. Varicella vaccination is also recommended for susceptible adolescents and adults who will have close contact with persons at high risk for serious complications of acquired varicella, including healthcare personnel and susceptible family contacts of immunocompromised individuals. The ACIP recommends that all healthcare personnel be immune to varicella, either from a reliable history of prior varicella infection or vaccination, to reduce the risk of infection and its complications, and to decrease the possibility of transmission of varicella zoster virus to patients (Table 22. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155632/ doi: 10.1016/b978-0-7216-8974-6.50026-9 id: cord-316703-8kxx3034 author: Parera, Mariona title: Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date: 2012-08-01 words: 4193.0 sentences: 220.0 pages: flesch: 52.0 cache: ./cache/cord-316703-8kxx3034.txt txt: ./txt/cord-316703-8kxx3034.txt summary: The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The target specificity for the MAVS and TRIF cleavage sites was tested by coexpressing them with CHV or HCV NS3/4A protease constructs. coli cells coexpressing the lambda cI repressor with either MAVS or TRIF cleavage site and a CHV NS3/4A construct, lambda phage replicated up to 2,000-fold more efficiently than in cells expressing a CHV protease variant that included a substitution in catalytic residue S139 ( Fig. 3A and 3B). In this study, we tested the ability of CHV NS3/4A protease to specifically cleave the human adaptor proteins MAVS and TRIF. Canine orthologs of human MAVS and TRIF differ in sequence at the cleavage site processed by HCV NS3/4A protease; therefore, they were not tested in this study. abstract: Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV. url: https://www.ncbi.nlm.nih.gov/pubmed/22870331/ doi: 10.1371/journal.pone.0042481 id: cord-343902-hzh3cjzh author: Peel, Michael title: Cyclophilin inhibitors as antiviral agents date: 2013-08-15 words: 4055.0 sentences: 184.0 pages: flesch: 48.0 cache: ./cache/cord-343902-hzh3cjzh.txt txt: ./txt/cord-343902-hzh3cjzh.txt summary: Initial reports of CsA inhibiting HIV-1 surfaced in 1988, 25 although the first report specifically implicating CypA involvement in the HIV-1 life cycle was published five years later when it was reported that endogenous CypA colocalizes with the HIV-1 Gag protein in the cytoplasm, binding specifically to a Pro-rich sequence in the HIV-1 capsid domain of Gag. 26 X-ray crystallography later revealed that residues 85-93 of HIV-1 capsid bind to the active site of CypA, 27 and subsequent studies have shown that virions produced in the presence of Gag mutated in the CypA binding region, or under pressure from competitive CypA inhibitors, were less infectious than wild type virions. 36 Further support for CypA being the primary Cyp involved in HCV RNA replication include a demonstration that the catalytic PPIase activity of CypA is required for efficient HCV RNA replication, and the finding that a specific binding between CypA and NS5A is dissociable by addition of CsAbased Cyp inhibitors. abstract: Cyclophilins (Cyps) are ubiquitous proteins that effect the cis–trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ∼19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key roles in effective replication of a number of viruses from different families. A drug template for CypA inhibition is cyclosporine A (CsA), a cyclic undecapeptide that simultaneously binds to both CypA and the Ca(2+)-dependent phosphatase calcineurin (CN), and can attenuate immune responses. Synthetic modifications of the CsA scaffold allows for selective binding to CypA and CN separately, thus providing access to novel, non-immunosuppressive antiviral agents. url: https://www.ncbi.nlm.nih.gov/pubmed/23849880/ doi: 10.1016/j.bmcl.2013.05.101 id: cord-300154-3p7tjp5j author: Pezacki, John Paul title: Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy date: 2011-02-14 words: 7750.0 sentences: 370.0 pages: flesch: 39.0 cache: ./cache/cord-300154-3p7tjp5j.txt txt: ./txt/cord-300154-3p7tjp5j.txt summary: Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. abstract: Cellular biomolecules contain unique molecular vibrations that can be visualized by coherent anti-Stokes Raman scattering (CARS) microscopy without the need for labels. Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. The CARS imaging modality provides a unique tool for biological chemists to elucidate the state of a cellular environment without perturbing it and to perceive the functional effects of added molecules. url: https://doi.org/10.1038/nchembio.525 doi: 10.1038/nchembio.525 id: cord-314254-9ye8tfvz author: Pfaender, Stephanie title: Natural reservoirs for homologs of hepatitis C virus date: 2014-03-26 words: 6841.0 sentences: 322.0 pages: flesch: 47.0 cache: ./cache/cord-314254-9ye8tfvz.txt txt: ./txt/cord-314254-9ye8tfvz.txt summary: To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaciand pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Non-primate hepaciviruses (NPHV) were initially discovered in domestic dogs and subsequently in horses 12, 13 and other diverse and widespread HCV-like viruses have been reported in wild populations of rodents and bats. Furthermore, liver function analyses revealed no indication for hepatic inflammation as c-glutamyl transferase and glutamate dehydrogenase values were within reference range, with the exception of a mildly elevated c-glutamyl transferase New HCV-like viruses in different mammalian hosts Pfaender et al 4 level in one horse. abstract: Hepatitis C virus is considered a major public health problem, infecting 2%–3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen. url: https://doi.org/10.1038/emi.2014.19 doi: 10.1038/emi.2014.19 id: cord-340220-raqapqg0 author: Potel, Julie title: EWI‐2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry date: 2013-02-16 words: 11314.0 sentences: 623.0 pages: flesch: 56.0 cache: ./cache/cord-340220-raqapqg0.txt txt: ./txt/cord-340220-raqapqg0.txt summary: We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w monoclonal antibodies (mAbs) (Silvie et al., 2006) to analyse the role of tetraspanin web-associated CD81 in HCV infection. Interestingly, as shown for one representative cell clone, cells expressing EWI-2wint exhibited a stronger staining with MT81w, indicating that EWI-2wint modifies CD81 membrane organization, probably by increasing the association of CD81 with the tetraspanin web. To strengthen the hypothesis that EWI-2wint induces a change in CD81 organization at the plasma membrane, we next analysed the membrane dynamics and partitioning of human CD81 (hCD81) molecules in Huh-7 cells expressing or lacking EWI-2wint by single-molecule fluorescence microscopy, which is a method of choice to characterize the diffusion of proteins and lipids in different regions of the plasma membrane (Owen et al., 2009 ). D. Huh-7w7/mCD81 clones expressing pcDNA3.1, EWI-2 or EWI-2wint were stained with MT81 and MT81w mAbs followed by PE-labelled secondary antibody and analysed by flow cytometry. abstract: CD81 is a major receptor for Hepatitis C Virus (HCV). It belongs to the tetraspanin family whose members form dynamic clusters with numerous partner proteins and with one another, forming tetraspanin‐enriched areas in the plasma membrane. In our study, we combined single‐molecule microscopy and biochemistry experiments to investigate the clustering and membrane behaviour of CD81 in the context of cells expressing EWI‐2wint, a natural inhibitor of HCV entry. Interestingly, we found that EWI‐2wint reduces the global diffusion of CD81 molecules due to a decrease of the diffusion rate of mobile CD81molecules and an increase in the proportion of confined molecules. Indeed, we demonstrated that EWI‐2wint promotes CD81 clustering and confinement in CD81‐enriched areas. In addition, we showed that EWI‐2wint influences the colocalization of CD81 with Claudin‐1 – a co‐receptor required for HCV entry. Together, our results indicate that a change in membrane partitioning of CD81 occurs in the presence of EWI‐2wint. This study gives new insights on the mechanism by which HCV enters into its target cells, namely by exploiting the dynamic properties of CD81. url: https://www.ncbi.nlm.nih.gov/pubmed/23351194/ doi: 10.1111/cmi.12112 id: cord-261287-l4649du3 author: Puoti, Massimo title: A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients() date: 2004-05-06 words: 3674.0 sentences: 151.0 pages: flesch: 43.0 cache: ./cache/cord-261287-l4649du3.txt txt: ./txt/cord-261287-l4649du3.txt summary: However, a cumulative sustained virological response (SVR) was observed in only 22% (95% Confidence interval (CI), 14 -30%) of 111 patients enrolled in four pilot uncontrolled studies aiming to assess the efficacy and tolerability of ribavirin plus interferon alfa1 administered thrice weekly in HIV/HCV co-infected patients [4 -7] . In order to establish that the SVR in the triple therapy arm is at least three times higher than the 18% sustained response rate observed in HIV-co-infected patients treated with interferon and ribavirin in pilot studies [4] [5] [6] [7] , it was calculated that at least 64 patients should have been enrolled. In conclusion, intensification of interferon alpha schedule and amantadine addition do not appear to improve the limited efficacy of standard combination therapy including interferon thrice weekly plus ribavirin for the treatment of chronic hepatitis C in HIV-co-infected patients. abstract: BACKGROUND/AIMS: Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients. METHODS: Multicentre, prospective, open-label, randomized, phase III clinical trial. Eighty co-infected patients were randomized to receive ribavirin 800–1000 mg/day in combination with, group A: interferon alpha2a 3 MIU thrice weekly; group B: IFNα2a 3 MIU daily, plus amantadine 200 mg/day; treatment duration was 24–48 weeks according to HCV genotype. RESULTS: Forty-one patients were randomized in group A and 39 in group B. Intention-to-treat analysis showed a sustained virological response, defined as HCV-RNA negativization, 6 months after stopping treatment in 22% of patients from group A and 13% from group B (P>0.05). The lack of a 2-log drop in HCV-RNA levels after 12 weeks of treatment showed a 100% predictive value of lack of sustained response. CONCLUSIONS: Amantadine addition and interferon intensification do not improve the low efficacy of combination of interferon alfa plus ribavirin in HIV/HCV co-infected patients. Patients with no early virologic response did not have any probability of sustained response. url: https://www.ncbi.nlm.nih.gov/pubmed/15288482/ doi: 10.1016/j.jhep.2004.04.016 id: cord-345898-a6vt8kso author: Ren, Linzhu title: Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses date: 2016-01-04 words: 6000.0 sentences: 289.0 pages: flesch: 38.0 cache: ./cache/cord-345898-a6vt8kso.txt txt: ./txt/cord-345898-a6vt8kso.txt summary: There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. An RVP is a type of virus-like particle (VLP) composed of viral structural proteins and a self-replicating replicon RNA containing a reporter gene [17, 63] . However, when the cells were infected with the specific virus, the viral RdRp was provided by the virus and the defective replicon was activated, resulting in high-level expression of the reporter gene, which could be easily examined [44] . However, when the cells were infected with the specific virus, the viral RdRp was provided by the virus and the defective replicon was activated, resulting in high-level expression of the reporter gene, which could be easily examined [44] . Development of Dengue type-2 virus replicons expressing GFP reporter gene in study of viral RNA replication abstract: Cell-based reporter systems have facilitated studies of viral replication and pathogenesis, virus detection, and drug susceptibility testing. There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. The first type is classical reporter system, which relies on recombinant virus, reporter virus particle, or subgenomic replicon. During infection with the recombinant virus or reporter virus particle, the reporter protein is expressed and can be detected in real time in a dose-dependent manner. Using subgenomic replicon, which are genetically engineered viral RNA molecules that are capable of replication but incapable of producing virions, the translation and replication of the replicon could be tracked by the accumulation of reporter protein. The second type of reporter system involves genetically engineered cells bearing virus-specific protease cleavage sequences, which can sense the incoming viral protease. The third type is based on viral replicase, which can report the specific virus infection via detection of the incoming viral replicase. This review specifically focuses on the major technical breakthroughs in the design of cell-based reporter systems and the application of these systems to the further understanding and control of viruses over the past few decades. url: https://doi.org/10.1007/s12010-015-1968-5 doi: 10.1007/s12010-015-1968-5 id: cord-294842-aesiff1f author: Romero-Brey, Inés title: Membranous Replication Factories Induced by Plus-Strand RNA Viruses date: 2014-07-22 words: 11038.0 sentences: 520.0 pages: flesch: 40.0 cache: ./cache/cord-294842-aesiff1f.txt txt: ./txt/cord-294842-aesiff1f.txt summary: Three-dimensional reconstructions of the WNV KUN replication sites revealed an intimate association of the rough ER (rER) with the bounding membrane of the VPs [20] (Figure 2B ), resembling the vesicles observed in DENV-infected cells. In cells infected with TBEV, one of the most important tick-transmitted viruses in Europe and Asia, virus particles and membrane-connected vesicles were also observed inside the ER [25] , similar to what was described for DENV and WNV KUN . Importantly, pulse-radiolabeling experiments localized sites of active RNA replication to the outer surface of single-membrane tubules [71] and isolation of the membranous replication factories and their subsequent visualization by EM revealed that they form rosette-like structures composed of virus-induced cytoplasmic vesicles [124] . Formation of plant RNA virus replication complexes on membranes: Role of an endoplasmic reticulum-targeted viral protein abstract: In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments. url: https://doi.org/10.3390/v6072826 doi: 10.3390/v6072826 id: cord-274080-884x48on author: Rumlová, Michaela title: In vitro methods for testing antiviral drugs date: 2018-06-30 words: 17989.0 sentences: 941.0 pages: flesch: 41.0 cache: ./cache/cord-274080-884x48on.txt txt: ./txt/cord-274080-884x48on.txt summary: For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. abstract: Abstract Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/29292156/ doi: 10.1016/j.biotechadv.2017.12.016 id: cord-321505-m40s6uw9 author: Sakamoto, Naoya title: Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA date: 2007-08-07 words: 4424.0 sentences: 253.0 pages: flesch: 45.0 cache: ./cache/cord-321505-m40s6uw9.txt txt: ./txt/cord-321505-m40s6uw9.txt summary: Background and Aim: We have reported previously that synthetic small interfering RNA (siRNA) and DNA‐based siRNA expression vectors efficiently and specifically suppress hepatitis C virus (HCV) replication in vitro. Intravenous delivery of the adenovirus expressing shRNA into transgenic mice that can be induced to express HCV structural proteins by the Cre/loxP switching system resulted in specific suppression of virus protein synthesis in the liver. Here, we report that HCV replication was suppressed in vitro by recombinant retrovirus and adenovirus vectors expressing short hairpin RNA (shRNA) and that the delivery of the adenovirus vector to mice in vivo specifically inhibited viral protein synthesis in the liver. These results indicated that the decrease in luciferase activities was due to specific suppressive effects of shRNA on expression of HCV genomic RNA and the viral proteins, and not due to non-specific effects caused by the delivery of shRNA or to toxicity of the adenovirus vectors. abstract: Background and Aim: We have reported previously that synthetic small interfering RNA (siRNA) and DNA‐based siRNA expression vectors efficiently and specifically suppress hepatitis C virus (HCV) replication in vitro. In this study, we investigated the effects of the siRNA targeting HCV‐RNA in vivo. Methods: We constructed recombinant retrovirus and adenovirus expressing short hairpin RNA (shRNA), and transfected into replicon‐expressing cells in vitro and transgenic mice in vivo. Results: Retroviral transduction of Huh7 cells to express shRNA and subsequent transfection of an HCV replicon into the cells showed that the cells had acquired resistance to HCV replication. Infection of cells expressing the HCV replicon with an adenovirus expressing shRNA resulted in efficient vector delivery and expression of shRNA, leading to suppression of the replicon in the cells by ∼10(−3). Intravenous delivery of the adenovirus expressing shRNA into transgenic mice that can be induced to express HCV structural proteins by the Cre/loxP switching system resulted in specific suppression of virus protein synthesis in the liver. Conclusion: Taken together, our results support the feasibility of utilizing gene targeting therapy based on siRNA and/or shRNA expression to counteract HCV replication, which might prove valuable in the treatment of hepatitis C. url: https://www.ncbi.nlm.nih.gov/pubmed/17683479/ doi: 10.1111/j.1440-1746.2007.05076.x id: cord-326217-ji0njeha author: Saleh, Maged title: Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122 date: 2018-11-27 words: 4731.0 sentences: 262.0 pages: flesch: 48.0 cache: ./cache/cord-326217-ji0njeha.txt txt: ./txt/cord-326217-ji0njeha.txt summary: We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. To assess whether both GSK3 isoforms are required for HCV replication, we silenced GSK3α and / or GSK3β gene expression by transfecting siRNAs and quantified HCV RNA in Huh-7.5 cells harboring HCV subgenomic replicon (Con1) or infectious HCV (Jc1). Given the well-known dependency of HCV on miR-122 (Jopling et al., 2005 (Jopling et al., , 2008 Machlin et al., 2011) and the regulatory circuit between insulin-like growth factor 1 receptor, GSK3β, and miR-122 identified previously (Zeng et al., 2010) , we assessed the effect of GSK3 inhibition on miR-122 expression in Huh-7.5 cells harboring a subgenomic HCV replicon. abstract: Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression. url: https://www.ncbi.nlm.nih.gov/pubmed/30542341/ doi: 10.3389/fmicb.2018.02949 id: cord-318853-mxyxwkhx author: Sallie, Richard title: Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases date: 2005-08-22 words: 10541.0 sentences: 396.0 pages: flesch: 25.0 cache: ./cache/cord-318853-mxyxwkhx.txt txt: ./txt/cord-318853-mxyxwkhx.txt summary: Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. Hence, as relative concentrations of wild-type and variant viral proteins vary, alteration of both processivity and fidelity of RNA pol results, permitting viruses to adaptively respond to environmental changes, including immune recognition and reaction to evolving cell receptors. As clear evidence exists for viral disruption of leptin function [106] and virus-associated weight gain in humans [107] and monkeys [108] , is it possible the global epidemics of type II diabetes mellitus, insulin resistance, hyperlipidaemia and obesity now prevalent [109] [110] [111] [112] [113] [114] [115] [116] , are just that; epidemics fundamentally caused by viruses that co-opt insulin or leptin or other associated receptors for cell access and generate protein quasispecies that disrupt receptor function? abstract: Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – "Viral Receptor Disease (VRD)" – may explain so-called "viral autoimmunity", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations. url: https://www.ncbi.nlm.nih.gov/pubmed/16115320/ doi: 10.1186/1743-422x-2-70 id: cord-321230-b5a1z14w author: Samji, Hasina title: Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada date: 2020-10-19 words: 5467.0 sentences: 225.0 pages: flesch: 48.0 cache: ./cache/cord-321230-b5a1z14w.txt txt: ./txt/cord-321230-b5a1z14w.txt summary: Lastly, if an underlying cause of death code was recorded as ICD-10 R99 (other ill-defined and unspecified causes, usually assigned when cause of death is still under investigation), and manner of death was listed as "pending," "accident," or "undetermined," we re-categorized the death as drug-related if the death met the following criteria: attributable to a person aged 20 to 64 years who also injects drugs (defined as any drug-related diagnoses, use of injection drugs, record of opioid agonist therapy dispensation or injection related infection using physician diagnostic and billing data, hospitalizations, prescription data, vital statistics and emergency room data), based on validation studies in the US and in the BC-HTC (Centers for Disease Control and Prevention, 2004; to mitigate the impact of missing data on the analysis. We compared PLHCV and HCV-negative individuals who died of DRDs, estimated annual age and sex-adjusted drug-related mortality rates per 100,000 person-years (PY) for these groups and examined trends over time by sex. abstract: BACKGROUND: The majority of new HCV infections in Canada occur in people who inject drugs. Thus, while curative direct antiviral agents (DAAs) herald a promising new era in hepatitis C virus (HCV) treatment, improving the lives and wellbeing of people living with HCV (PLHCV) must be considered in the context of reducing overdose-related harms and with a syndemic lens. We measure drug-related deaths (DRDs) among HCV-negative people and PLHCV in British Columbia (BC), Canada, and the impact of potent contaminants like fentanyl on deaths. METHODS: We identified DRDs among PLHCV and HCV-negative individuals from 2010 to 2018 in the BC Hepatitis Testers Cohort, a population-based dataset of ~1.7 million British Columbians comprising comprehensive administrative and clinical data. We estimated annual standardized liver- and drug-related mortality rates per 100,000 person-years (PY) and described the contribution of specific drugs, including fentanyl and its analogues, implicated in DRDs over time. RESULTS: DRDs constituted 20.1% of deaths among PLHCV and 4.7% of deaths among HCV-negative individuals; a 4.3-fold (95% confidence interval: 4.0-4.5) difference. Drug-related mortality overtook liver-related mortality for PLHCV in 2015 and HCV-negative individuals in 2016 and rose from 241.7 to 436.5 per 100,000 PY from 2010 to 2018 amongPLHCV and from 20.0 to 57.1 per 100,000 PY for HCV-negative individuals over the same period. The proportion of deaths attributable to drugs among PLHCV and HCV-negative individuals increased from 15.1% to 26.1% and 3.1% to 8.0%, in 2010 and 2018, respectively. The proportion of DRDs attributed solely to synthetic opioids such as fentanyl averaged across both groups increased from 2.1% in 2010 to 69.6% in 2017. Conclusion: Steep drug-related mortality increases among PLHCV and HCV-negative individuals over the last decade highlight the urgent need to address overdose-related drivers and harms in these populations using an integrated care approach. url: https://www.ncbi.nlm.nih.gov/pubmed/33091735/ doi: 10.1016/j.drugpo.2020.102989 id: cord-256036-gd53s4dv author: Sandmann, Lisa title: Barriers of hepatitis C virus interspecies transmission date: 2013-01-01 words: 7894.0 sentences: 373.0 pages: flesch: 40.0 cache: ./cache/cord-256036-gd53s4dv.txt txt: ./txt/cord-256036-gd53s4dv.txt summary: In contrast to human hepatocytes, murine cells do not support HCV entry thereby creating a first and important barrier for a broader host tropism of the virus. Utilizing blocking antibodies specific to CD81 or the viral envelope protein E2, expression of entry factor mutants and mice with a targeted disruption of the SCARB1 gene validated uptake of HCV into murine hepatocytes in an HCV glycoprotein-mediated fashion. Taking advantage of the high mutational plasticity of HCV, three adaptive mutations in the viral glycoproteins E1 and E2 were identified that allowed the virus to enter cells expressing human SCARB1, CLDN1, OCLN and mouse CD81. Recently, a genetically humanized mouse model was constructed utilizing cell culture produced recombinant hepatitis C virus to activate a cellular encoded reporter (Dorner et al., 2011, in press ). Human occludin is a hepatitis C virus entry factor required for infection of mouse cells A humanized mouse model to study Hepatitis C virus infection, immune response, and liver disease abstract: Hepatitis C virus (HCV) is a major causative agent of severe liver disease including fibrosis, cirrhosis and liver cancer. Therapy has improved over the years, but continues to be associated with adverse side effects and variable success rates. Furthermore, a vaccine protecting against HCV infection remains elusive. Development of more effective intervention measures has been delayed by the lack of a suitable animal model. Naturally, HCV infects only humans and chimpanzees. The determinants of this limited host range are poorly understood in part due to difficulties of studying HCV in cell culture. Some progress has been made elucidating the barriers for the HCV lifecycle in non-permissive species which will help in the future to construct animal models for HCV infection, immunity and pathogenesis. url: https://doi.org/10.1016/j.virol.2012.09.044 doi: 10.1016/j.virol.2012.09.044 id: cord-302295-nblmshni author: Savva, Athina title: Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases date: 2013-11-18 words: 10282.0 sentences: 533.0 pages: flesch: 39.0 cache: ./cache/cord-302295-nblmshni.txt txt: ./txt/cord-302295-nblmshni.txt summary: TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Recombinant human activated protein C (rhAPC, Xigris®, Eli Lilly), the only drug specifically registered for sepsis, has recently been withdrawn from the market following the negative results from the PROWESS-SHOCK study that did not show reduction in mortality at 28 or 90 days in patients with septic shock (4) . The discovery of TLRs and their involvement in innate immune responses has attracted much interest into the development of drugs for controlling infections and improving sepsis management. Moreover, upon infection, innate immune cells will likely sense several MAMPs via several TLRs and non-TLR PRRs. For example, Gram-negative bacteria express MAMPs that may trigger redundant inflammatory pathways through TLR2 (lipopeptides), TLR4 (LPS), TLR5 (flagellin), TLR7 (ssRNA), and TLR9 (bacterial DNA). abstract: Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis. url: https://www.ncbi.nlm.nih.gov/pubmed/24302927/ doi: 10.3389/fimmu.2013.00387 id: cord-268467-btfz6ye8 author: Schreiber, Steven S. title: Sequence analysis of the nucleocapsid protein gene of human coronavirus 229E date: 1989-03-31 words: 5035.0 sentences: 343.0 pages: flesch: 59.0 cache: ./cache/cord-268467-btfz6ye8.txt txt: ./txt/cord-268467-btfz6ye8.txt summary: The 3′-noncoding region of the genome contains an 11-nucleotide sequence, which is relatively conserved throughout the Coronavirus family and lends support to the theory that this region is important for the replication of negative-strand RNA. This result suggested that the HCV229E subgenomic mRNAs possess a nested-set structure similar to other coronaviruses and that A34 represented a cDNA clone of either the 3''-end of the genomic RNA or the leader sequence. The 3''-noncoding region contains the sequence TGGAAGAGCCA, 75 nucleotides from the 3''-end (Fig. 4) which is relatively conserved among coronaviruses and is found at approximately the same location in all of these viral genomes (Kapke and Brian, 1986; Skinner and Siddell, 1984; Armstrong et a/., 1983; Lapps et al., 1987; Kamahora et a/., 1988; Boursnell et al., 1985) ( Table 1) . Three intergenic regions of coronavirus mouse hepatitis virus strain A59 genome RNA contain a common nucleotide sequence that is homologous to the 3''end of the viral mRNA leader sequence abstract: Abstract Human coronaviruses are important human pathogens and have also been implicated in multiple sclerosis. To further understand the molecular biology of human coronavirus 229E (HCV-229E), molecular cloning and sequence analysis of the viral RNA have been initiated. Following established protocols, the 3′-terminal 1732 nucleotides of the genome were sequenced. A large open reading frame encodes a 389 amino acid protein of 43,366 Da, which is presumably the nucleocapsid protein. The predicted protein is similar in size, chemical properties, and amino acid sequence to the nucleocapsid proteins of other coronaviruses. This is especially evident when the sequence is compared with that of the antigenically related porcine transmissible gastroenteritis virus (TGEV), with which a region of 46% amino acid sequence homology was found. Hydropathy profiles revealed the existence of several conserved domains which could have functional significance. An intergenic consensus sequence precedes the 5′-end of the proposed nucleocapsid protein gene. The consensus sequence is present in other coronaviruses and has been proposed as the site of binding of the leader sequence for mRNA transcriptional start. This region was also examined by primer extension analysis of mRNAs, which identified a 60-nucleotide leader sequence. The 3′-noncoding region of the genome contains an 11-nucleotide sequence, which is relatively conserved throughout the Coronavirus family and lends support to the theory that this region is important for the replication of negative-strand RNA. url: https://api.elsevier.com/content/article/pii/0042682289900500 doi: 10.1016/0042-6822(89)90050-0 id: cord-000833-m6abyuvx author: Sekiguchi, Satoshi title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date: 2012-12-17 words: 5915.0 sentences: 348.0 pages: flesch: 50.0 cache: ./cache/cord-000833-m6abyuvx.txt txt: ./txt/cord-000833-m6abyuvx.txt summary: The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. These observations, in addition to the modified histology activity index (HAI) scores, indicated that expression of HCV proteins caused chronic hepatitis in the CN2-29 (+/2) /MxCre (+/2) mice because a weak, though persistent, immune response followed an initial bout of acute hepatitis ( Figure S1 ). To determine whether activation of the host immune response caused the reduction with HCV protein levels in the livers of CN2-29 (+/2) /MxCre (+/2) mice, we used a highly attenuated VV strain, LC16m8, to generate three rVVs [12] . To determine whether rVV-N25 treatment induced the same effect in other strains of HCV transgenic mice, we analyzed RzCN5-15 (+/2) /MxCre (+/2) mice, which express all HCV proteins; in these mice, chronic hepatitis was resolved within 28 days of immunization with rVV-N25. abstract: Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/−))/MxCre((+/−)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524174/ doi: 10.1371/journal.pone.0051656 id: cord-305303-82n96ukr author: Shapira, Assaf title: Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date: 2012-02-16 words: 10132.0 sentences: 431.0 pages: flesch: 42.0 cache: ./cache/cord-305303-82n96ukr.txt txt: ./txt/cord-305303-82n96ukr.txt summary: As shown in Figure 2 , similar numbers of surviving colonies were observed when the cells were transfected with the plasmids encoding mCherry-NS3 activated MazF or the red fluorescent protein alone, suggesting that expression of NS3-activable ribonuclease in naïve HEK293 T-REx cells (that do not express NS3) cause minimal toxicity, if any. The ER membrane-targeted zymoxin colocalizes with NS3 protease in vivo Previously we described a HEK293 cell line which inducibly expresses (by addition of tetracycline) a fusion between EGFP and the coding sequence of the full length NS3 (including the helicase domain) followed by NS4A from HCV 1a genotype [10] . When infection reached ,50% (about 50% of the cultured cells showed expression of the HCV-core protein, as detected by immuno-staining and fluorescence microscopy), the mixed culture and a culture of uninfected cells were treated with NS3 activated MazF or uncleavable-MazF encoding adenoviruses at MOI of ,3. abstract: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases. url: https://www.ncbi.nlm.nih.gov/pubmed/22359682/ doi: 10.1371/journal.pone.0032320 id: cord-279202-iyteg4h9 author: Shesheer Kumar, Munpally title: Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients date: 2008-01-05 words: 2088.0 sentences: 119.0 pages: flesch: 53.0 cache: ./cache/cord-279202-iyteg4h9.txt txt: ./txt/cord-279202-iyteg4h9.txt summary: title: Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients Apart from the core (21 kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the −2/+1 reading frame. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Functional properties of a 16 kDa protein translated from an alternative open reading frame of the core encoding genomic region of hepatitis C virus abstract: Apart from the core (21 kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the −2/+1 reading frame. To date, no information is available on F1 protein of Indian isolates, and hence detection of antibodies for F1 protein in Indian patients assumes great relevance. Specific primers have been designed to amplify sequence coding for 120aa of truncated F1 (tF1). The amplified tF1 has been cloned in bacterial expression vector, pET21b for expression in Escherichia coli. Partially purified expressed protein has been subjected to western blot analysis using patients’ sera. Three HCV positive sera employed in western analysis showed positive signals to tF1, while sera from uninfected individuals failed to give any signals. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Presence of antibodies against F1 protein of subtype 1c has been demonstrated, for the first time, in Indian patients. url: https://www.sciencedirect.com/science/article/pii/S1567134808000038 doi: 10.1016/j.meegid.2007.12.008 id: cord-284551-j0nooxmd author: Shinohara, Yoshiyasu title: Unfolded protein response pathways regulate Hepatitis C virus replication via modulation of autophagy date: 2013-03-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Hepatitis C virus (HCV) induces endoplasmic reticulum (ER) stress which, in turn, activates the unfolding protein response (UPR). UPR activates three distinct signalling pathways. Additionally, UPR induces autophagy (UPR-autophagy pathways). On the other hand, it has become clear that some positive-single-strand RNA viruses utilize autophagy. Some groups have used the siRNA silencing approach to show that autophagy is required for HCV RNA replication. However, the mechanism of induction of the UPR-autophagy pathways remain unclear in the cells with HCV. Method and results: we used a genome-length HCV RNA (strain O of genotype 1b) replication system (OR6) in hepatoma cells (HuH-7-derived OR6 cells). As control, we used OR6c cells from which the HCV genome had been removed by treatment with interferon-α. The UPR-autophagy pathways were activated to a greater degree in the OR6 cells as compared to the OR6c cells. Rapamycin, mTOR-independent autophagy inducer, activated HCV replication in the OR6 cells. On the other hand, HCV replication in the cells was inhibited by 3-methyladenine (3-MA), which is an inhibitor of autophagy. Salubrinal (Eukaryotic Initiation Factor 2(eIF2)-alpha phosphatase inhibitor), 3-ethoxy-5, 6-dibromosalicylaldehyde (X-box binding protein-1 (XBP-1) splicing inhibitor) and sp600125 (c-Jun N-terminal kinases (JNK) inhibitor) inhibited HCV replication and autophagy. Additionally, HCV replication and autophagy were inhibited more strongly by combination of these inhibitors. CONCLUSION: Our results suggest that UPR-autophagy pathways exert an influence on HCV replication. Therefore, control these pathways may serve as a novel therapeutic strategy against replication of HCV. url: https://api.elsevier.com/content/article/pii/S0006291X13001939 doi: 10.1016/j.bbrc.2013.01.103 id: cord-010273-0c56x9f5 author: Simmonds, Peter title: Virology of hepatitis C virus date: 2001-10-10 words: 7897.0 sentences: 337.0 pages: flesch: 41.0 cache: ./cache/cord-010273-0c56x9f5.txt txt: ./txt/cord-010273-0c56x9f5.txt summary: 1,2 The identification of HCV led to the development of diagnostic assays for infection, based either on detection of antibody to recombinant polypeptides expressed from cloned HCV sequences or direct detection of virus ribonucleic acid (RNA) sequences by polymerase chain reaction (PCR) using primers complimentary to the HCV genome. 6 ''13 Remarkably, a series of plant viruses that are structurally distinct from each of the mammalian virus groups, and with different genome organizations, have RNA-dependent RNA polymerase amino acid sequences that are perhaps more similar to those of HCV than are the flaviviruses. In contrast to the highly restricted sequence diversity of the 5''NCR and adjacent core region, the two putative envelope genes are highly divergent between different variants of HCV (Table III) 111-114 and show a three-to-four-times higher rate of sequence change with time in persistently infected patients, ll5 Because these proteins are likely to lie on the outside of the virus, they would be the principal targets of the humoral immune response to HCV elicited on infection. abstract: Hepatitis C virus (HCV) has been identified as the main causative agent of post-transfusion non-A, non-B hepatitis. Through recently developed diagnostic assays, routine serologic screening of blood donors has prevented most cases of post-transfusion hepatitis. The purpose of this paper is to comprehensively review current information regarding the virology of HCV. Recent findings on the genome organization, its relationship to other viruses, the replication of HCV ribonucleic acid, HCV translation, and HCV polyprotein expression and processing are discussed. Also reviewed are virus assembly and release, the variability of HCV and its classification into genotypes, the geographic distribution of HCV genotypes, and the biologic differences between HCV genotypes. The assays used in HCV genotyping are discussed in terms of reliability and consistency of results, and the molecular epidemiology of HCV infection is reviewed. These approaches to HCV epidemiology will prove valuable in documenting the spread of HCV in different risk groups, evaluating alternative (nonparenteral) routes of transmission, and in understanding more about the origins and evolution of HCV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173289/ doi: 10.1016/s0149-2918(96)80193-7 id: cord-000174-mgj9zfft author: Slavenburg, Serena title: Pneumonitis as A Consequence of (Peg)Interferon-Ribavirin Combination Therapy for Hepatitis C: a Review of the Literature date: 2009-04-28 words: 3198.0 sentences: 178.0 pages: flesch: 40.0 cache: ./cache/cord-000174-mgj9zfft.txt txt: ./txt/cord-000174-mgj9zfft.txt summary: Pulmonary toxicity in patients undergoing HCV combination treatment is rare, and may include interstitial pneumonitis, sarcoidosis, pleuritis, bronchiolitis obliterans organizing pneumonia (BOOP), and exacerbation of asthma [6, 7] . Interstitial pneumonitis occurs only rarely as a side-effect of HCV combination treatment and often leads to discontinuation of therapy, which has great implications for patients. In this article we presented our case of pneumonitis during combination therapy and performed a review in order to generate guidelines to manage symptoms and treatment. In most cases, symptoms of pneumonitis are reversible after cessation of treatment with (peg)interferon and ribavirin, again in support of drug-induced interstitial pneumonitis. Severe interstitial pneumonitis secondary to pegylated interferon alpha-2b and ribavirin treatment of hepatitis C infection Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C. Interstitial pneumonitis during combination therapy with interferon-a and ribavirin in a patient with chronic hepatitis C Interstitial pneumonitis after combination therapy with pegylated interferon alpha-2b and ribavirin for chronic hepatitis C abstract: Combination of peginterferon and ribavirin is the current therapy for chronic hepatitis C infection (HCV). Interstitial pneumonitis is a rare side-effect of HCV therapy and is an important cause of dose reduction or discontinuation, impairing success of antiviral therapy. We performed a review of the literature in order to present diagnostic modalities and possible treatments for pneumonitis and to offer guidelines. We searched for cases where pneumonitis as a side-effect of HCV treatment was documented. First we performed a literature search via PubMed and Web of Science interface and second we searched three drug toxicity databases. We systematically analyzed all case reports with respect to clinical manifestations, type of treatment, and outcome. A literature search revealed 19 articles, containing 25 case descriptions, while we traced 33 cases from the drug toxicity databases. Pneumonitis presented with any of the combination of fever, dyspnea, and cough and can arise with any type of (conventional or pegylated) interferon. Mortality secondary to pneumonitis was seen in 7% of cases, exclusively with peginterferon α-2b. In most cases therapy was discontinued and steroids were started. Interferon-induced pneumonitis during HCV treatment is a severe complication and should be recognized in order to prevent further pulmonary damage and/or death. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822957/ doi: 10.1007/s10620-009-0797-1 id: cord-253768-y35m3vh1 author: Springer, Sandra A title: Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA’s Advocacy Agenda date: 2020-10-01 words: 5844.0 sentences: 262.0 pages: flesch: 41.0 cache: ./cache/cord-253768-y35m3vh1.txt txt: ./txt/cord-253768-y35m3vh1.txt summary: Nevertheless, a number of barriers to care in people who use drugs need to be addressed to end the opioid and HIV epidemics in the United States as well as reduce the other infectious disease health outcomes. To address these barriers we recommend expanding Medicaid, expanding access to harm reduction services, improving treatment and surveillance to enhance the continuum of care, and treating opioid and other substance use disorders (SUD), including through lowbarrier hospital and community-based treatment, as well as in the criminal justice setting. Increased state and federal funding are needed to expand SSP and other harm reduction services, including access to MOUD and infectious diseases treatment services in order to decrease HCV, HIV, IDU-related infections, and vaccine-preventable diseases, and improve OUD-related outcomes [26, 27] . abstract: In response to the opioid crisis, IDSA and HIVMA established a working group to drive an evidence- and human rights-based response to illicit drug use and associated infectious diseases. Infectious diseases and HIV physicians have an opportunity to intervene, addressing both conditions. IDSA and HIVMA have developed a policy agenda highlighting evidence-based practices that need further dissemination. This paper reviews (1) programs most relevant to infectious diseases in the 2018 SUPPORT Act; (2) opportunities offered by the “End the HIV Epidemic” initiative; and (3) policy changes necessary to affect the trajectory of the opioid epidemic and associated infections. Issues addressed include leveraging harm reduction tools and improving integrated prevention and treatment services for the infectious diseases and substance use disorder care continuum. By strengthening collaborations between infectious diseases and addiction specialists, including increasing training in substance use disorder treatment among infectious diseases and addiction specialists, we can decrease morbidity and mortality associated with these overlapping epidemics. url: https://doi.org/10.1093/infdis/jiz673 doi: 10.1093/infdis/jiz673 id: cord-342676-ykog278j author: Stewart, H. title: Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date: 2016-03-14 words: 6858.0 sentences: 338.0 pages: flesch: 46.0 cache: ./cache/cord-342676-ykog278j.txt txt: ./txt/cord-342676-ykog278j.txt summary: To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We wished to investigate the possibility that similar specific secondary structures are present within HCV RNAs destined for packaging, and whether their interactions with Core cooperatively drive the RNA encapsidation and nucleocapsid assembly processes. A mutant genome unable to form such structures displays impaired viral infectivity whilst RNA replication is unaffected, indicating these motifs may interact specifically with Core. Role of RNA structures in genome terminal sequences of the hepatitis C virus for replication and assembly abstract: The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly. url: https://www.ncbi.nlm.nih.gov/pubmed/26972799/ doi: 10.1038/srep22952 id: cord-256769-flfycl7i author: Stoermer, Kristina A. title: Complement and Viral Pathogenesis date: 2011-03-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection. url: https://www.sciencedirect.com/science/article/pii/S0042682210008135 doi: 10.1016/j.virol.2010.12.045 id: cord-258234-qn8xp4v9 author: Striker, Rob title: Inhibitors of Peptidyl Proline Isomerases As Antivirals in Hepatitis C and Other Viruses date: 2014-11-06 words: 2485.0 sentences: 132.0 pages: flesch: 38.0 cache: ./cache/cord-258234-qn8xp4v9.txt txt: ./txt/cord-258234-qn8xp4v9.txt summary: Cyclophilin inhibitors that reduce viral replication also block interactions between cyclophilin A and NS5A, suggesting that this association is important during the viral life cycle and might be the relevant target of the antiviral activity of cyclosporine [11] [12] [13] . HCV NS5A is a protein that is rich in both proline residues and disorder and that associates with cyclophilin A via domain 2. However, these regions share several common properties: the flexible cyclophilin-interacting loop in CA is also bracketed by prolines, just as the PAWARPDYNP motif in HCV; residues 86, 91, and 96 that surround the glycine-proline in CA influence viral susceptibility to cyclophillin inhibitors similar to mutations surrounding NS5A P319 [25] ; and the critical glycine-proline is amino-terminal to regions of CA that are actually more proline rich and predicted by bioinformatics analysis to be disordered, analogous to the positioning of the PAWARPDYNP motif in HCV NS5A. abstract: nan url: https://doi.org/10.1371/journal.ppat.1004428 doi: 10.1371/journal.ppat.1004428 id: cord-273555-i1d4quos author: Stättermayer, A. F. title: Letter: does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks? Authors'' reply date: 2014-02-04 words: 1159.0 sentences: 64.0 pages: flesch: 47.0 cache: ./cache/cord-273555-i1d4quos.txt txt: ./txt/cord-273555-i1d4quos.txt summary: Authors'' reply SIRS, We thank Dr Galmozzi and Dr Lampertico for their comment on our recently published paper on the effect of the dinucleotide frameshift variant in ss469415590 in the interferon (IFN)-k4 gene on interferon/ribavirin treatment and its relationship with the two commonly used single nucleotide polymorphisms (SNP) in IL28B (rs12979860, rs8099917). 1, 2 We agree that our study does not provide insights on the causal relationship between IFNL4 and treatment response in patients with chronic hepatitis C virus (HCV) infection. We would like to remind them that up-regulation of intrahepatic interferon-stimulated genes (ISG) is associated with treatment failure in patients with chronic HCV, and levels of ISG are differently distributed according to different IL28B genotypes. 1 reported a randomised controlled trial comparing oral (100 mg twice daily ferrous sulphate for 3 months) or intravenous (1000 mg ferric carboxymaltose, single-dose infusion) iron supplementation and placebo for anaemia after nonvariceal upper gastrointestinal (GI) bleeding. abstract: nan url: https://doi.org/10.1111/apt.12626 doi: 10.1111/apt.12626 id: cord-007236-8hiymqyb author: Sun, Ji-Min title: Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway date: 2011-11-09 words: 4983.0 sentences: 276.0 pages: flesch: 47.0 cache: ./cache/cord-007236-8hiymqyb.txt txt: ./txt/cord-007236-8hiymqyb.txt summary: title: Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway We demonstrated that a group of Monascus orange pigment (MOP) derivatives effectively inhibited NS5B RdRp activity and interfered with the mevalonate synthesis pathway, thereby suppressing HCV replication in cells harbouring an HCV genotype 1b subgenomic replicon and in cells infected with genotype 2a HCV. As shown in Figure 2 (a), among the selected group of MOP AADs that inhibited NS5B RdRp activity in vitro, Lys, Phe, Val, Leu and Ile derivatives also inhibited HCV replication in Huh7 cells, which harbour a HCV subgenomic replicon RNA. Together, these results suggest that in addition to a direct inhibition of NS5B RdRp activity, these MOP AAD compounds also inhibit HCV replication by interfering with the cholesterol biosynthetic pathway downstream of the HMG-CoA reductase step. abstract: OBJECTIVES: Hepatitis C virus (HCV) infection causes chronic liver disease and is a major public health problem worldwide. The aim of this study was to evaluate the potential of Monascus pigment derivatives, which were derived from a microbial secondary metabolite synthesized from polyketides by Monascus spp., as HCV antiviral agents. METHODS: We performed an in vitro RNA-dependent RNA polymerase (RdRp) assay to screen for HCV RdRp inhibitors. The anti-HCV activity of RdRp inhibitors in HCV-replicating cells was evaluated by quantification of the RNA viral genome. Molecular docking analysis was performed to predict the binding sites of the selected RdRp inhibitors. RESULTS: We have identified a Monascus pigment and its derivatives as inhibitors of the HCV NS5B RdRp. A group of Monascus orange pigment (MOP) amino acid derivatives, in which the reactive oxygen moiety was changed to amino acids, significantly inhibited HCV replication. Further, combination of the MOP derivatives (Phe, Val or Leu conjugates) with interferon (IFN)-α inhibited HCV replication more than IFN-α treatment alone. Lastly, molecular docking studies indicate the inhibitors may bind to a thumb subdomain allosteric site of NS5B. The antiviral activity of the MOP derivatives was related to a modulation of the mevalonate pathway, since the mevalonate-induced increase in HCV replication was suppressed by the MOP compounds. CONCLUSIONS: Our results identify amino acid derivatives of MOP as potential anti-HCV agents and suggest that their combination with IFN-α might offer an alternative strategy for the control of HCV replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109977/ doi: 10.1093/jac/dkr432 id: cord-001834-6xf4o3oy author: Sung, Pil Soo title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection date: 2015-10-07 words: 4039.0 sentences: 230.0 pages: flesch: 44.0 cache: ./cache/cord-001834-6xf4o3oy.txt txt: ./txt/cord-001834-6xf4o3oy.txt summary: In HCV-infected cells, viral RNA is sensed by retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA-5) in the cytoplasm and Toll-like receptor 3 (TLR3) in the endosome, which leads to downstream signaling that results in the induction of type III and I IFNs and other inflammatory cytokines [28, [36] [37] [38] [39] . Intracellular signals from RIG-I, MDA-5, and TLR3 are transmitted via mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1 receptor domain-containing adaptor inducing IFN- (TRIF), respectively, which leads to the interferon regulatory factor-3 (IRF-3)-dependent induction of IFNs and NF-κB activation in HCV-infected cells [38, 39] . IFN-s activate the same JAK-STAT pathway as type I IFNs [48] [49] [50] , thereby inducing a similar set of ISGs. Although the exact source of IFN-s in HCV-infected liver remains to be clarified, it seems that the production of IFN-s by HCV-infected hepatocytes results in the expression of ISGs, presumably through autocrine and/or paracrine signaling via the IFN-λ receptor [28, [44] [45] [46] . HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons abstract: Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130–170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632721/ doi: 10.3390/ijms161023683 id: cord-281389-sht0yx4a author: Tal, Michal Caspi title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date: 2020-06-23 words: 7629.0 sentences: 382.0 pages: flesch: 46.0 cache: ./cache/cord-281389-sht0yx4a.txt txt: ./txt/cord-281389-sht0yx4a.txt summary: Examination of a publicly available gene expression data set (Gene Expression Omnibus [GEO] accession number GSE147507) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of A549 human lung cells also showed a significant upregulation of CD47 compared to mock-infected controls (Fig. 1D ). Multiple PBMC subsets showed significantly upregulated CD47 expression in response to Borrelia burgdorferi infection compared to naive cells (Fig. 1E) . Overall, the combined in vivo and in vitro results from multiple pathogen infections in both human and mouse cells indicated that the upregulation of CD47 was a conserved host response possibly related to host sensing mechanisms. Compared to healthy controls, monocytes and DCs from HCV patients demonstrated a sustained upregulation of CD47 at all treatment time points, including the 6-month posttreatment time point ( Fig. 3B (B) CD47 MFI on human total PBMCs from 4 separate donors stimulated with titrated concentrations of R848 from 0.1 g/ml to 10 g/ml, as indicated, for 48 h. abstract: It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 “don’t eat me” signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis. Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents. url: https://www.ncbi.nlm.nih.gov/pubmed/32576678/ doi: 10.1128/mbio.01293-20 id: cord-330110-pamxy4av author: Teissier, Elodie title: Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date: 2011-01-25 words: 9268.0 sentences: 438.0 pages: flesch: 48.0 cache: ./cache/cord-330110-pamxy4av.txt txt: ./txt/cord-330110-pamxy4av.txt summary: Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. By combining surface plasmon resonance, fluorescence and NMR spectroscopy approaches, we showed that Arb directly interacts with the phospholipid membrane interface, with an affinity in the micromolar range, comparable to the concentration inhibiting HCVpp membrane fusion by 50% (IC50). Altogether our results demonstrate that Arb interacts with the polar head of phospholipid membranes and protein motifs enriched in aromatic residues, suggesting that the inhibitory activity of Arb on HCV entry and fusion could involve both types of interactions. Conversely, Arb inhibition of HCVpp membrane fusion, as assessed by a in vitro model system where the only proteins present are the viral glycoproteins, could merely reflect the interaction of Arb on lipids and/or on motifs present in HCV glycoproteins of any genotype. abstract: The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection. url: https://doi.org/10.1371/journal.pone.0015874 doi: 10.1371/journal.pone.0015874 id: cord-265592-r8nlef0h author: Teuber, G. title: Randomized, placebo‐controlled, double‐blind trial with interferon‐α with and without amantadine sulphate in primary interferon‐α nonresponders with chronic hepatitis C date: 2001-12-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In primary interferon‐α (IFN‐α) nonresponders with chronic hepatitis C, retreatment with IFN‐α has only limited efficacy with sustained response rates below 10%. Therefore, the aims of the present study were to compare the efficacy and safety of IFN‐α alone or in combination with amantadine sulphate in nonresponders to previous IFN‐α monotherapy. Fifty‐five IFN‐α nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN‐α 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks. Amantadine sulphate (n=26) or a matched placebo (n=29) was given orally twice daily for 48 weeks. Because of a low initial response rate at week 12 (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN‐α dose reduction in week 24, a virological end‐of‐treatment response with undetectable serum HCV‐RNA (< 1000 copies/mL) was achieved in only five patients (IFN‐α/amantadine sulphate, one patient; IFN‐α/placebo, four patients). After 24 weeks follow‐up a sustained virological response was observed in only two patients receiving IFN‐α and placebo. Health‐related quality‐of‐life analysis showed a substantial improvement of the Profile of Mood States (POMS) scale concerning the subscales fatigue (P < 0.05) and vigor (P < 0.05) in patients receiving combined IFN‐α/amantadine sulphate treatment compared with those treated with IFN‐α alone. IFN‐α/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN‐α and amantadine sulphate does not increase the low sustained virological response rates of IFN‐α therapy in primary IFN‐α nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health‐related quality‐of‐life. url: https://www.ncbi.nlm.nih.gov/pubmed/11454179/ doi: 10.1046/j.1365-2893.2001.00297.x id: cord-280878-1kt51viz author: To, Janet title: Targeting the Channel Activity of Viroporins date: 2016-01-07 words: 15297.0 sentences: 701.0 pages: flesch: 47.0 cache: ./cache/cord-280878-1kt51viz.txt txt: ./txt/cord-280878-1kt51viz.txt summary: For other viroporins, these studies are still mostly in their infancy, although a highresolution structure of the hepatitis C virus (HCV) p7 protein has been recently described (Ouyang et al., 2013) that may be useful for the rational design of p7 channel inhibitors in the future. Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels NMR structure and ion channel activity of the p7 protein from hepatitis C virus Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus abstract: Since the discovery that certain small viral membrane proteins, collectively termed as viroporins, can permeabilize host cellular membranes and also behave as ion channels, attempts have been made to link this feature to specific biological roles. In parallel, most viroporins identified so far are virulence factors, and interest has focused toward the discovery of channel inhibitors that would have a therapeutic effect, or be used as research tools to understand the biological roles of viroporin ion channel activity. However, this paradigm is being shifted by the difficulties inherent to small viral membrane proteins, and by the realization that protein–protein interactions and other diverse roles in the virus life cycle may represent an equal, if not, more important target. Therefore, although targeting the channel activity of viroporins can probably be therapeutically useful in some cases, the focus may shift to their other functions in following years. Small-molecule inhibitors have been mostly developed against the influenza A M2 (IAV M2 or AM2). This is not surprising since AM2 is the best characterized viroporin to date, with a well-established biological role in viral pathogenesis combined the most extensive structural investigations conducted, and has emerged as a validated drug target. For other viroporins, these studies are still mostly in their infancy, and together with those for AM2, are the subject of the present review. url: https://doi.org/10.1016/bs.apcsb.2015.12.003 doi: 10.1016/bs.apcsb.2015.12.003 id: cord-351365-dc9t3vh3 author: Todt, Daniel title: Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date: 2016-10-13 words: 6318.0 sentences: 320.0 pages: flesch: 40.0 cache: ./cache/cord-351365-dc9t3vh3.txt txt: ./txt/cord-351365-dc9t3vh3.txt summary: Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. Figure 1 provides an overview of a selection of RNA viruses against which RBV was shown to be active: hepatitis C virus (HCV, Flaviviridae), dengue virus (DENV, Flaviviridae), respiratory syncytial virus (RSV, Paramyxoviridae), influenza A and B virus (Orthomyxoviridae), chikungunya virus (CHIKV, Togaviridae), poliovirus (Picornaviridae), Hantaan virus (Bunyaviridae), and Lassa virus (Arenaviridae) [28, 29] ( Figure 1 ). Furthermore, mechanisms on the virus itself were described by inhibition of the capping efficiency, the viral polymerase, and a mutagenic effect on newly synthesized RNA genomes. A Mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients abstract: Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/27754363/ doi: 10.3390/v8100283 id: cord-265005-e6rpryrh author: Tomasello, Elena title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 words: 18082.0 sentences: 948.0 pages: flesch: 40.0 cache: ./cache/cord-265005-e6rpryrh.txt txt: ./txt/cord-265005-e6rpryrh.txt summary: We will discuss the expression patterns and functions of endosomal TLRs with regards to IFN production in uninfected specialized immune cell types, pDCs and XCR1 + DCs. Plasmacytoid DCs uniquely produce very large amounts of IFNs in response to in vitro stimulation with many viruses, without being infected (46) . Under these conditions, to promote health over disease, the benefits for the host of producing high circulating levels of IFNs in order to induce widespread cell-intrinsic anti-viral defenses might prevail over the deleterious effects that this could cause on certain cell types or tissues. Subcapsular sinus macrophages rapidly become infected by viruses incoming from the lymph and produce large amounts of IFNs. This altruistic suicide prevents virus dissemination to other adjacent cell types and promotes the induction of innate and adaptive anti-viral immunity (87) . abstract: Type I interferons (IFN-I) were identified over 50 years ago as cytokines critical for host defense against viral infections. IFN-I promote anti-viral defense through two main mechanisms. First, IFN-I directly reinforce or induce de novo in potentially all cells the expression of effector molecules of intrinsic anti-viral immunity. Second, IFN-I orchestrate innate and adaptive anti-viral immunity. However, IFN-I responses can be deleterious for the host in a number of circumstances, including secondary bacterial or fungal infections, several autoimmune diseases, and, paradoxically, certain chronic viral infections. We will review the proposed nature of protective versus deleterious IFN-I responses in selected diseases. Emphasis will be put on the potentially deleterious functions of IFN-I in human immunodeficiency virus type 1 (HIV-1) infection, and on the respective roles of IFN-I and IFN-III in promoting resolution of hepatitis C virus (HCV) infection. We will then discuss how the balance between beneficial versus deleterious IFN-I responses is modulated by several key parameters including (i) the subtypes and dose of IFN-I produced, (ii) the cell types affected by IFN-I, and (iii) the source and timing of IFN-I production. Finally, we will speculate how integration of this knowledge combined with advanced biochemical manipulation of the activity of the cytokines should allow designing innovative immunotherapeutic treatments in patients. Specifically, we will discuss how induction or blockade of specific IFN-I responses in targeted cell types could promote the beneficial functions of IFN-I and/or dampen their deleterious effects, in a manner adapted to each disease. url: https://www.ncbi.nlm.nih.gov/pubmed/25400632/ doi: 10.3389/fimmu.2014.00526 id: cord-306934-29ljbl7g author: Tonelli, Michele title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date: 2009-07-01 words: 8526.0 sentences: 442.0 pages: flesch: 58.0 cache: ./cache/cord-306934-29ljbl7g.txt txt: ./txt/cord-306934-29ljbl7g.txt summary: Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values. First of all, the binding site identified by our procedure is very close to the putative binding site proposed for two allosteric inhibitors of BVDV RdRp, VP32947 and BPIP, 23 Table 5 Cytotoxicity against MT-4, MDBK, BHK and Vero-76 cell lines and YFV, Reo-1, CVB-2, RSV, HSV-1 and Sb-1 inhibitory activity of triazene derivatives of structure F and G Tables 3 and 4. In view of these considerations, molecular modeling investigations were performed to study wether the active compounds of structures A-C could target the BVDV RNA-dependent RNA-polymerase (RdRp), which shares some structural similarity with HCV RdRp. Indeed a good agreement was observed between the trend exhibited by the IC 50 (calculated from the estimated free energies of binding) and the corresponding biological activities determined for these compounds in BVDV infected MDBK cell line. abstract: Abstract Twelve aminoarylazocompounds (A–C) and 46 aryltriazene 7 derivatives (D–G) have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. Eight aminoazocompounds and 27 aryltriazene derivatives exhibited antiviral activity, sometimes of high level, against one or more viruses. A marked activity against BVDV and YFV was prevailing among the former compounds, while the latter type of compounds affected mainly CVB-2 and RSV. None of the active compounds inhibited the multiplication of HIV-1, VSV and VV. Arranged in order of decreasing potency and selectivity versus the host cell lines, the best compounds are the following; BVDV: 1 > 7 > 8 > 4; YFV: 7 > 5; CVB-2: 25 > 56 > 18; RSV: 14 > 20 > 55 > 38 > 18 > 19; HSV-1: 2. For these compounds the EC50 ranged from 1.6μM (1) to 12μM (18), and the S. I. from 19.4 (1) to 4.2 (2). Thus the aminoarylazo and aryltriazene substructures appear as interesting molecular component for developing antiviral agents against ss RNA viruses, particularly against RSV and BVDV, which are important human and veterinary pathogens. Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values. url: https://www.ncbi.nlm.nih.gov/pubmed/19482481/ doi: 10.1016/j.bmc.2009.05.020 id: cord-270498-hh6h50t2 author: Tseng, Chin-Kai title: Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date: 2017-09-19 words: 4954.0 sentences: 277.0 pages: flesch: 47.0 cache: ./cache/cord-270498-hh6h50t2.txt txt: ./txt/cord-270498-hh6h50t2.txt summary: Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. In this study, our data revealed that celastrol significantly inhibits HCV replication, and that the anti-HCV effect of celastrol was attenuated by the HO-1 specific inhibitor tin mesoporphyrin (SnMP) or HO-1 gene expression silencing. Celastrol-mediated HO-1 induction contributed to the anti-HCV action through inducing antiviral IFN response and inhibiting HCV NS3 protease activity. As shown in Fig. 7B , HO-1 RNA expression levels were induced by celastrol compared with non-celastrol treated cells and the JNK inhibitor SP600125 significantly reduced the HO-1 inductive effect of celastrol. In the present study, we found that a natural product celastrol could effectively inhibit HCV NS3/4A protease activity and enhance IFN-mediated antiviral gene expression through HO-1 induction (Figs. abstract: BACKGROUND AND PURPOSE: Celastrol, a quinone methide triterpene isolated from the root extracts of Tripterygium wilfordii, can greatly induce the gene expression activity of heme oxygenase-1 (HO-1) to achieve disease prevention and control. HO-1 induction was recently shown to result in anti-HCV activity by inducing type I interferon and inhibiting hepatitis C virus (HCV) NS3/4A protease activity. The aim of the present study is to evaluate the anti-HCV activity of celastrol and characterize its mechanism of inhibition. METHODS: The anti-HCV activity of celastrol was evaluated using the HCV subgenomic replicon and HCVcc infection systems. The anti-HCV mechanism of celastrol targeting HO-1 expression was clarified using specific inhibitors against several signaling pathways. The transcriptional regulation of celastrol on target gene expression was determined using promoter-based reporter activity assay. The synergistic effect of celastrol and a numbers of clinically used anti-HCV drugs was determined via a drug combination assay. RESULTS: Celastrol inhibited HCV replication in both the HCV subgenomic and HCVcc infection systems with EC50 values of 0.37 ± 0.022 and 0.43 ± 0.019 μM, respectively. Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. JNK mitogen-activated protein kinase and nuclear factor erythroid 2-related factor 2 (Nrf2) were confirmed to be involved in the inductive effect of celastrol on HO-1 expression. Celastrol exhibited synergistic effects in combination with interferon-alpha, the NS5A inhibitor daclatasvir, and the NS5B inhibitor sofosbuvir. CONCLUSION: Celastrol can serve as a potential supplement for blocking HCV replication. Targeting the JNK/Nrf2/HO-1 axis presents a promising strategy against HCV infection. url: https://doi.org/10.1016/j.antiviral.2017.09.010 doi: 10.1016/j.antiviral.2017.09.010 id: cord-000008-3dgjv0x1 author: Vali, Bahareh title: HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date: 2008-10-20 words: 5253.0 sentences: 236.0 pages: flesch: 47.0 cache: ./cache/cord-000008-3dgjv0x1.txt txt: ./txt/cord-000008-3dgjv0x1.txt summary: In response to stimulation with HIV peptide pool, untreated co-infected individuals showed significantly higher frequencies of intra-hepatic CD4 + T-cells producing IFN-c, compared to HCV mono-infected [0.1660.05% vs 0.0260.01%, p,0.05], and HAART-treated co-infected individuals [0.1660.05% vs 0.0360.05%, p,0.05] (Figure 2a ). Therapy naïve co-infected subjects had greater IFN-c producing CD8 + T-cells in response to HIV peptides compared to HCV mono-infected individuals [1.3960.37% vs 0.0260.0%, p,0.05], and HAART was associated with a significant reduction in the frequencies of these cells [1.3960.37% vs 0.3060.26%, p,0.05] (figure 2b). The tetramer cytokine response pattern was shown to be different in the liver compared to blood of the same individual, with diminished intra-hepatic tetramer-specific IFN-c responses and an increase in both CD107a and TNF-a responses, with the majority of SL9 tetramer positive cells expressing these two markers. Therapy naïve co-infected individuals demonstrated a higher frequency of intra-hepatic CD8 + T-cells that produce TNF-a in response to both HCV and HIV antigen stimulation compared to HCV mono-infected individuals. abstract: BACKGROUND AND AIMS: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses. METHODS: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry. RESULTS: HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4(+) T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8(+) and CD4(+) T-cells producing IFN-γ and TNF-α were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8(+) T-cells produced more of the fibrogenic cytokine, TNF-α. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4(+) T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses. CONCLUSION: The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565067/ doi: 10.1371/journal.pone.0003454 id: cord-285505-8norumv6 author: Vere Hodge, R. Anthony title: Meeting report: 27th International conference on antiviral research, in Raleigh, NC, USA date: 2014-09-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The 27th International Conference on Antiviral Research (ICAR) was held in Raleigh, North Carolina, USA from May 12 to 16, 2014. This article summarizes the principal invited lectures. John Drach (Elion Award) described the early days of antiviral drugs and their novel modes of action. Piet Herdewijn (Holý Award) used evolutionary pressure to select DNA polymerases that accept nucleoside analogs. Replacing thymine by 5-chlorouracil led to the generation of a new form of Escherichia coli. Adrian Ray (Prusoff Award) demonstrated how prodrugs can markedly improve both the efficacy and safety of potential drugs. The keynote addresses, by David Margolis and Myron Cohen, tackled two emerging areas of HIV research, to find an HIV “cure” and to prevent HIV transmission, respectively. These topics were discussed further in other presentations – a cure seems to be a distant prospect but there are exciting developments for reducing HIV transmission. TDF-containing vaginal rings and GSK-744, as a long-lasting injection, offer great hope. There were three mini-symposia. Although therapy with TDF/FTC gives excellent control of HBV replication, there are only a few patients who achieve a functional cure. Myrcludex, an entry inhibitor, is active against both HBV and HDV. The recent progress with HBV replication in cell cultures has transformed the search for new antiviral compounds. The HBV capsid protein has been recognized as key player in HBV DNA synthesis. Unexpectedly, compounds which enhance capsid formation, markedly reduce HBV DNA synthesis. The development of BCX4430, which is active against Marburg and Ebola viruses, is of great current interest. url: https://api.elsevier.com/content/article/pii/S0166354214002460 doi: 10.1016/j.antiviral.2014.08.009 id: cord-264713-38dlh3wg author: Vernet, Guy title: Molecular diagnostics in virology date: 2004-08-20 words: 4798.0 sentences: 233.0 pages: flesch: 42.0 cache: ./cache/cord-264713-38dlh3wg.txt txt: ./txt/cord-264713-38dlh3wg.txt summary: Viral load and antiviral resistance or subtyping assays are now part of the biological monitoring of patients chronically infected by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV. The most striking illustration of the power of molecular techniques concerns blood transmitted viruses-human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) for which spectacular progresses in the detection and treatment of viral diseases have been made following the introduction of qualitative and quantitative nucleic acid tests (NAT). For example, we have observed, using a DNA-microarray assay (see below), that the analytical sensitivity of multiplex RT-PCR detection of six viruses, i.e. influenza A, influenza B, RSV A/B, parainfluenza 1, 2 and 3 is reduced by a factor of <1-2 logs compared to single detections, depending on the virus. abstract: Molecular biology has significantly improved diagnosis in the field of clinical virology. Virus discovery and rapid implementation of diagnostic tests for newly discovered viruses has strongly beneficiated from the development of molecular techniques. Viral load and antiviral resistance or subtyping assays are now part of the biological monitoring of patients chronically infected by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV. It will be important to add to this panel assays for other viruses of the herpesviridae family. Qualitative assays for the detection of blood-borne viruses have increased safety of blood donation and organ transplantation. Screening of other blood-borne viruses (parvovirus B19, HAV), multiplexing of detection and test automation to improve practicability and reduce costs will be the next steps. A major evolution in the near future will be the generalization of NAT for the diagnosis of viral etiology in patients, mostly with respiratory, CNS or gastro-intestinal diseases. Major technical improvements have been made to avoid obstacles that still limit this generalization, i.e. genetic variability of viruses, multiplex detection, contamination risk. Commercial offers already exist but menus must be extended to limit the validation and documentation work associated with home-brew assays. Real-time amplification has allowed the development of new NAT platforms but automation and integration of all steps of the reaction are still required to reduce hands-on-time, time-to-result and costs, and to increase throughput. url: https://www.sciencedirect.com/science/article/pii/S1386653204001696 doi: 10.1016/j.jcv.2004.06.003 id: cord-347710-ff64y6ef author: Wan, Qianya title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 words: 36567.0 sentences: 2487.0 pages: flesch: 46.0 cache: ./cache/cord-347710-ff64y6ef.txt txt: ./txt/cord-347710-ff64y6ef.txt summary: hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. 6, 13 It is well known that Hsp90 not only interacts and contributes to RNA polymerase assembly and nuclear import of some (−) ssRNA viruses (e.g., PB2 of influenza virus), but plays crucial roles in the folding process of viral capsid proteins and virion assemblies as well. 17, 18 As a critical component of cellular protein surveillance, the ATP-dependent molecular chaperone protects cells from damage caused by stress and takes part in a number of folding processes, including folding of newly synthesized polypeptides, recognition and refolding of misfolded or aggregated proteins, solubilization or degradation of proteins, transporting proteins, assembly or disassembly of oligomeric protein complexes, and the regulation of certain natively folded proteins. abstract: Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson’s diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation. url: https://www.ncbi.nlm.nih.gov/pubmed/32661235/ doi: 10.1038/s41392-020-00233-4 id: cord-305263-fgwf6wy3 author: Wang, Ben X. title: The yin and yang of viruses and interferons date: 2012-02-07 words: 6285.0 sentences: 294.0 pages: flesch: 38.0 cache: ./cache/cord-305263-fgwf6wy3.txt txt: ./txt/cord-305263-fgwf6wy3.txt summary: IFN therapy therefore has the advantage over DAA treatments in that, in addition to stimulating genes that block viral replication in infected cells, IFNs activate other innate and adaptive immune responses to combat the virus. For example, polymorphisms in host genes encoding proteins associated with regulation of an IFN response such as interferon receptor a-chain (IFNAR1) [10] , the IFN-inducible myxovirus resistance GTPase protein, Mx [11] , the IFN-inducible 2 0 ,5 0 -oligoadenylate synthetase (OAS) [12] and the suppressor of cytokine signaling (SOCS) 3 associated with regulation of an IFN response [13] , are predictive markers linked with the rate of sustained virological response (SVR) to HCV infection following IFN-a treatment. Remarkably, distinct highly pathogenic respiratory viruses, namely influenza viruses and the SARS-CoV, encode nonstructural proteins in their genomes that function as virulence factors that specifically target the host innate IFN response, further emphasizing the importance of IFNs as broad-spectrum antivirals. abstract: Interferons (IFNs)-α/β are critical effectors of the innate immune response to virus infections. Through activation of the IFN-α/β receptor (IFNAR), they induce expression of IFN-stimulated genes (ISGs) that encode antiviral proteins capable of suppressing viral replication and promoting viral clearance. Many highly pathogenic viruses have evolved mechanisms to evade an IFN response and the balance between the robustness of the host immune response and viral antagonistic mechanisms determines whether or not the virus is cleared. Here, we discuss IFNs as broad-spectrum antivirals for treatment of acute virus infections. In particular, they are useful for treatment of re-emerging virus infections, where direct-acting antivirals (DAAs) have limited utility due to DAA-resistant mutations, and for newly emerging virus strains in which the time to vaccine availability precludes vaccination at the onset of an outbreak. url: https://doi.org/10.1016/j.it.2012.01.004 doi: 10.1016/j.it.2012.01.004 id: cord-259916-gr6v098c author: Wang, Hongliang title: Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication date: 2016-05-20 words: 6186.0 sentences: 252.0 pages: flesch: 33.0 cache: ./cache/cord-259916-gr6v098c.txt txt: ./txt/cord-259916-gr6v098c.txt summary: Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication. A later study of cells containing a subgenomic HCV replicon reported that the membrane alterations induced by HCV replication consisted in part of double-membrane vesicles (DMVs; Figure 1 ) with a diameter around 200 nm that were also positive on immunoelectron microscopy with antibodies against NS5A and double-stranded RNA (dsRNA) [15] . [10] first showed that expression of viral nonstructural proteins resulted in membrane alterations that morphologically resemble those observed in replicon cells, demonstrating that viral RNA replication is not required for membranous web formation. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex abstract: Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). Assembling replication factors at a membranous structure might facilitate the processes necessary for genome replication and packaging and shield viral components from host innate immune defenses. The biogenesis of the HCV MW is a complex process involving a concerted effort of HCV nonstructural proteins with a growing list of host factors. Although a comprehensive understanding of MW formation is still missing, a number of important viral and host determinants have been identified. This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication. url: https://doi.org/10.3390/v8050142 doi: 10.3390/v8050142 id: cord-003158-mhlqnj52 author: Wang, Qi title: Adapted HCV JFH1 variant is capable of accommodating a large foreign gene insert and allows lower level HCV replication and viral production date: 2018-07-13 words: 5186.0 sentences: 291.0 pages: flesch: 56.0 cache: ./cache/cord-003158-mhlqnj52.txt txt: ./txt/cord-003158-mhlqnj52.txt summary: Previous studies have demonstrated that the HCV JFH1 NS5A C-terminal is a flexible region which is capable of accommodating foreign gene inserts (such as EGFP, 720bp and Rennilla luciferase [Rluc] , 930bp) and still permit HCV replication and viral production (18, 19, (24) (25) (26) (27) (28) (29) . In this study, we used the JFH1-AM120 as a vector to explore if infectious reporter virus would be produced following insertion of LacZ gene that was three time larger than Rluc, into the NS5A C-terminus. This result provided evidence that fusion protein of NS5A and β-galactosidase can be co-expressed in Huh7.5 cells after transfection of JFH1-AM120-LacZ RNA. Our results demonstrate that the LacZ reporter gene can be inserted into the NS5A C-terminus of HCV JFH1-AM120 and will express the predicted NS5A-LacZ fusion protein, which can be detected by western blotting three days after RNA transfection of cells. abstract: Infectious HCV carrying reporter genes have further applications in understanding the HCV life cycle including replication, viral assembly and release. In this study, a full-length 3039bp LacZ gene was inserted into the derivative of JFH1-AM120 to develop an additional reporter virus. The results showed that the recombinant reporter virus JFH1-AM120-LacZ can replicate and produce lower titers of infectious virus. However, insertion of the LacZ gene in the C-terminal region of the NS5A in HCV JFH1-AM120-LacZ decreased viral replication and dramatically impaired the production of infectious viral particles. Moreover, the JFH1-AM120-LacZ reporter virus lost the LacZ gene after serial passage. Nevertheless, the JFH1-AM120-LacZ reporter virus displayed the entire life cycle of HCV, from replication to production of infectious virus, in Huh7.5 cells. This study demonstrates that the NS5A region of HCV JFH1-AM120 has the capacity to accommodate large foreign genes up to 3,039 bp and suggests that other relatively large gene inserts can be accommodated at this site. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097470/ doi: 10.7150/ijbs.27411 id: cord-293653-u2qrxq6t author: Watashi, Koichi title: Cyclophilin and Viruses: Cyclophilin as a Cofactor for Viral Infection and Possible Anti-Viral Target date: 2007-02-05 words: 4891.0 sentences: 304.0 pages: flesch: 46.0 cache: ./cache/cord-293653-u2qrxq6t.txt txt: ./txt/cord-293653-u2qrxq6t.txt summary: In addition to these cellular events, a number of reports demonstrated that CyP plays a critical role in the life cycle of viruses, especially human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The action of PPIases leads to changes in protein conformation (Takahashi, 1999) , but the binding of CsA and FK506 to CyP and FKBP, respectively, inhibits the activity of these enzymes (Fischer et al. The CsA/CyP or FK506/FKBP complex, subsequently interacts with and inhibits calcineurin (CN), a phosphatase involved in the activation of the transcription factor NF-AT. Members of the CyP family play roles in a variety of cellular processes including the immune response, transcription, mitochondrial function, cell death, and chemotaxis, as described below. However, the best-characterized role identified for CyPA is not in normal cellular physiology, but rather as co-factor during the human immunodefi ciency virus-1 (HIV-1) viral life cycle (See below). abstract: Cyclophilin (CyP) is a peptidyl prolyl cis/trans isomerase, catalyzing the cis-trans isomerization of proline residues in proteins. CyP plays key roles in several different aspects of cellular physiology including the immune response, transcription, mitochondrial function, cell death, and chemotaxis. In addition to these cellular events, a number of reports demonstrated that CyP plays a critical role in the life cycle of viruses, especially human immunodeficiency virus (HIV) and hepatitis C virus (HCV). These two viruses are significant causes of morbidity and mortality worldwide, but current therapies are often insufficient. CyP may provide a novel therapeutic target for the management and/or cure of these diseases, in particular HCV. url: https://www.ncbi.nlm.nih.gov/pubmed/21901058/ doi: nan id: cord-276364-zyw5aukk author: Wong, Ho Him title: Manipulation of autophagy by (+) RNA viruses date: 2019-08-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Autophagy is an evolutionarily conserved process central to host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention. url: https://www.sciencedirect.com/science/article/pii/S1084952118302222 doi: 10.1016/j.semcdb.2019.07.013 id: cord-343963-99rd3o79 author: Wong, Mun-Teng title: Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date: 2014-12-29 words: 17253.0 sentences: 1074.0 pages: flesch: 42.0 cache: ./cache/cord-343963-99rd3o79.txt txt: ./txt/cord-343963-99rd3o79.txt summary: 13, 14 Upon infection by viruses such as HCV, viral RNA is first sensed by cellular pattern recognition receptors (PRRs), and the PRR-mediated recruitment of adaptor proteins and the activation of downstream signaling lead to IFN production. First, we briefly discuss the signaling triggered by the retinoic acid-inducible gene 1-like receptor (RLR) and the Toll-like receptor (TLR), which leads to type I IFN synthesis and IFN-mediated signaling pathway activation, resulting in the expression of a variety of effector ISGs. We also summarize the strategies that HCV uses to escape IFN antiviral surveillance. 156 demonstrated that HCVinduced SG formation is IFN-and PKR-dependent and is inversely correlated with the induction of ISG proteins, such as myxovirus resistance gene A (MxA) and Ub-like (UBL)specific protease 18 (USP18), in HCV-infected cells without affecting the mRNA levels of these ISGs. Furthermore, the SG proteins TIA-1, TIAR and G3BP1 have been shown to play a critical role in HCV replication and infectious virus production. abstract: Infection with hepatitis C virus (HCV), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. HCV infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. Upon HCV infection, the host induces the interferon (IFN)-mediated frontline defense to limit virus replication. Conversely, HCV employs diverse strategies to escape host innate immune surveillance. Type I IFN elicits its antiviral actions by inducing a wide array of IFN-stimulated genes (ISGs). Nevertheless, the mechanisms by which these ISGs participate in IFN-mediated anti-HCV actions remain largely unknown. In this review, we first outline the signaling pathways known to be involved in the production of type I IFN and ISGs and the tactics that HCV uses to subvert innate immunity. Then, we summarize the effector mechanisms of scaffold ISGs known to modulate IFN function in HCV replication. We also highlight the potential functions of emerging ISGs, which were identified from genome-wide siRNA screens, in HCV replication. Finally, we discuss the functions of several cellular determinants critical for regulating host immunity in HCV replication. This review will provide a basis for understanding the complexity and functionality of the pleiotropic IFN system in HCV infection. Elucidation of the specificity and the mode of action of these emerging ISGs will also help to identify novel cellular targets against which effective HCV therapeutics can be developed. url: https://www.ncbi.nlm.nih.gov/pubmed/25544499/ doi: 10.1038/cmi.2014.127 id: cord-333331-ddcz7zck author: Yang, Jin title: Detection of hepatitis C virus by an improved loop-mediated isothermal amplification assay date: 2011-05-12 words: 5207.0 sentences: 245.0 pages: flesch: 54.0 cache: ./cache/cord-333331-ddcz7zck.txt txt: ./txt/cord-333331-ddcz7zck.txt summary: An improved, sensitive, specific, and rapid one-step reverse transcription loop-mediated isothermal amplification (LAMP) assay targeting the 5′ untranslated region (UTR) was developed to detect hepatitis C virus (HCV) infection. A variety of molecular diagnostic assays, such as reverse transcriptase PCR [12] , nucleic-acid-sequence-based amplification [13] , transcription-mediated amplification [29] , branched-chain DNA assay [26] , and in-house realtime PCR [8] , have been developed for the detection of HCV RNA. Confirmed cases of HCV infection were verified by a positive result in an enzyme-linked immunosorbent assay (Kehua Bio-engineering, Shanghai, China) for antibodies against HCV or a quantitative real-time PCR for HCV RNA. Given that the sensitivity of the AP-LAMP assay for detecting HCV is higher than that of the pre-LAMP method, the pathway of AP-based amplification was investigated. Reverse transcription-loop-mediated isothermal amplification assay for rapid detection of hepatitis E virus abstract: An improved, sensitive, specific, and rapid one-step reverse transcription loop-mediated isothermal amplification (LAMP) assay targeting the 5′ untranslated region (UTR) was developed to detect hepatitis C virus (HCV) infection. Based on an accelerating primer (AP), the present assay, named AP-LAMP, has the advantages of rapidity and sensitivity over the routine LAMP method. The possible AP-based amplification pathway during the reaction was revealed by restriction enzyme digestion and eletrophoresis. The detection limit of the AP-LAMP assay was approximately 84 IU/ml, and no cross-detection was observed. The assay was evaluated further with 126 clinical specimens, and the results indicated the suitability and simplicity of the test as a rapid diagnostic tool for detection of HCV RNA. url: https://doi.org/10.1007/s00705-011-1001-4 doi: 10.1007/s00705-011-1001-4 id: cord-006436-61mgtbj4 author: Yoshiba, Makoto title: Development of reliable artificial liver support (ALS)-plasma exchange in combination with hemodiafiltration using high-performance membranes date: 1993 words: 4449.0 sentences: 235.0 pages: flesch: 58.0 cache: ./cache/cord-006436-61mgtbj4.txt txt: ./txt/cord-006436-61mgtbj4.txt summary: A new artificial liver support system (ALSS) consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) using high-performance membranes of polymethyl metacrylate (PMMA) and cellulose triacetate (CTA) was developed to efficiently remove middle molecules from plasma and treat fulminant hepatic failure (FHF) complicated, by the onset of hepatic coma. It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those, awaiting liver transplantation. Preliminary use of this new ALSS has shown it to be effective in reversing grade V hepatic coma in a patient with fulminant liver failure (15) . A new ALSS system consisting of PE and HDF using high-performance membranes [polymethyl metacrylate (PMMA) and cellulose triacetate (CTA)] was devised to enhance the removal of the middle-Sized molecules thought to be responsible for hepatic coma. abstract: A new artificial liver support system (ALSS) consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) using high-performance membranes of polymethyl metacrylate (PMMA) and cellulose triacetate (CTA) was developed to efficiently remove middle molecules from plasma and treat fulminant hepatic failure (FHF) complicated, by the onset of hepatic coma. Twenty-seven patients with FHF due to viral hepatitis, two with type A (HA), nine with type B (HB), and 16 with type non-A, non-B (NANB) underwent therapy with this new ALSS over the last five years. Three patients, with an exacerbation of chronic HB and 15/16 with type NANB hepatitis were treated with interferon (IFN) also. Of these, 25 patients (92.6%), regained consciousness and 15 (55.6%) [1/2 (50%) with type A, 6/9 (66.7%) with type B and 8/16 (50%) with type NANB hepatitis] survived Including four patients who survived with intensive, care and plasma exchange alone, 19/31 (61.3%) patients survived. Because of its biocompatibility, both survivors and nonsurvivors could be sustained with the ALSS without complications for long periods (19.3 days for the survivors and 32.4 days for nonsurvivors). With this ALSS the ability to sustain life for such prolonged periods allows hepatic regeneration to occur and result in patient survival. It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those, awaiting liver transplantation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101817/ doi: 10.1007/bf01316501 id: cord-265588-1tcaleeo author: Yousaf, Tahir title: Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus date: 2018-03-20 words: 3480.0 sentences: 209.0 pages: flesch: 55.0 cache: ./cache/cord-265588-1tcaleeo.txt txt: ./txt/cord-265588-1tcaleeo.txt summary: title: Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus Therefore, this study was designed to find out phytochemicals and investigate antiviral activity of methanol extract of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus (HCV infection). Antiviral activity of the selected plant extract was find out against HCV infected HepG2 cells. Phytochemical analysis showed the presence of flavonoids and phenols in all plant extracts while amino acids, alkaloids and tannins were present in B. So, it was important to find out the toxic effects of four medicinal plants used in the current study before evaluating for anti-HCV activities. Antiviral activities of methanol extract of four medicinal plants were tested against HCV and results has been summarized in Fig. 2 for 24 h and Fig. 3 for 48 h treatments. abstract: Hepatitis C is a serious health issue and cause liver disorders in millions of people. Available therapeutic agents require long term administration with numerous side effects. Therefore, there is a dire need to find alternative treatment options for this disease. Since ancient times, medicinal plants are widely used to cure various diseases with no or less harmful effects. Therefore, this study was designed to find out phytochemicals and investigate antiviral activity of methanol extract of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus (HCV infection). Phytochemical analysis of the plant extract was performed using various chemical tests. Toxicity of the plant extract was determined against using trypan blue exclusion method. Antiviral activity of the selected plant extract was find out against HCV infected HepG2 cells. For this purpose, HepG2 cells were seeded with HCV positive and negative serum and nontoxic doses of plant extract for 24 and 48 h. After this RNA was extracted and viral load was determined using Real-time PCR. Phytochemical analysis showed the presence of flavonoids and phenols in all plant extracts while amino acids, alkaloids and tannins were present in B. lycium and saponins were detected in C. lemon. Toxicity assay showed that all plant extracts were nontoxic at maximum concentration of 200 μg/ml except B. lycium, which showed mild toxicity at 40 μg/ml and were extremely toxic at 60 μg/ml and above doses. Real-time PCR quantitation result revealed that after 24 h treatments A. parviflora showed highest antiviral activity, followed by A. bracteosa, while B. lycium extract had low (35%) and C. lemon has no antiviral effects. The 48 h treatments showed an increase antiviral activity by A. bracteosa followed by A. parviflora and B. lycium while C. lemon showed negative effect. Our results depicted that mentioned plants might be used as an alternative therapeutic regime or in combination with existing treatments against HCV. url: https://www.ncbi.nlm.nih.gov/pubmed/29571723/ doi: 10.1016/j.micpath.2018.03.030 id: cord-027860-s97hdhh6 author: Zeimet, Anthony title: Infectious Diseases date: 2020-06-22 words: 28925.0 sentences: 1728.0 pages: flesch: 45.0 cache: ./cache/cord-027860-s97hdhh6.txt txt: ./txt/cord-027860-s97hdhh6.txt summary: Although common upper respiratory bacterial pathogens, such as Moraxella (Branhamella) catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, may be isolated from patients with acute bronchitis, their relevance is questionable because these bacteria can be present in the respiratory tract of healthy individuals. In the treatment of Bordetella pertussis, early administration of a macrolide antibiotic and patient isolation will likely decrease coughing paroxysms and limit spread of disease (Braman, 2006) (SOR: A). Risk factors for Pseudomonas infection include severe structural lung disease (e.g., bronchiectasis) and recent antibiotic therapy, health care-associated exposures or stay in hospital (especially in the ICU). Patients who present with severe infection or whose infection is progressing despite empiric antibiotic therapy should be treated more aggressively; the treatment strategy should be based on results of appropriate Gram stain, culture, and drug susceptibility analysis. For suspected MRSA skin infections, oral treatment options include trimethoprim-sulfamethoxazole, clindamycin, and doxycycline of purulent material when performing incision and drainage in the event that the patient fails to improve and antibiotic coverage becomes necessary. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315328/ doi: 10.1016/b978-1-4377-1160-8.10016-8 id: cord-316968-rowoylge author: Zhang, Wenjuan title: Using maximum likelihood method to detect adaptive evolution of HCV envelope protein-coding genes date: 2006 words: 3532.0 sentences: 210.0 pages: flesch: 50.0 cache: ./cache/cord-316968-rowoylge.txt txt: ./txt/cord-316968-rowoylge.txt summary: Maximum likelihood (ML) method with codon-substitution models is a powerful statistic tool for detecting amino acid sites under positive selection and adaptive evolution. We analyzed the hepatitis C virus (HCV) envelope protein-coding sequences from 18 general geno/subtypes worldwide, and found 4 amino acid sites under positive selection. The purpose of this study is therefore to use the ML method [9] to infer adaptive evolution and positively selected amino acid sites of HCV envelope protein entire coding sequences containing all 6 HCV genotypes. We took HCV envelope glycoprotein as an example to explore the adaptive evolution driven by immune environment pressure of coding sequences of 27 HCV containing 18 geno/subtypes and found that a number of amino acid sites were under positive selection and ML could be employed for identifying the adaptive evolution of RNA virus on a large scale of genetic diversity. abstract: Nonsynonymous-synonymous substitution rate ratio (d (N)/d (S)) is an important measure for evaluating selective pressure based on the protein-coding sequences. Maximum likelihood (ML) method with codon-substitution models is a powerful statistic tool for detecting amino acid sites under positive selection and adaptive evolution. We analyzed the hepatitis C virus (HCV) envelope protein-coding sequences from 18 general geno/subtypes worldwide, and found 4 amino acid sites under positive selection. Since these sites are located in different immune epitopes, it is reasonable to anticipate that our study would have potential values in biomedicine. It also suggests that the ML method is an effective way to detect adaptive evolution in virus proteins with relatively high genetic diversity. url: https://www.ncbi.nlm.nih.gov/pubmed/32214724/ doi: 10.1007/s11434-006-2118-9 id: cord-324054-d71rj29o author: Zhang, Xuming title: The hemagglutinin/esterase gene of human coronavirus strain OC43: Phylogenetic relationships to bovine and murine coronaviruses and influenza C virus date: 1992-01-31 words: 2355.0 sentences: 147.0 pages: flesch: 64.0 cache: ./cache/cord-324054-d71rj29o.txt txt: ./txt/cord-324054-d71rj29o.txt summary: Abstract The complete nucleotide sequences of the hemagglutinin/esterase (HE) genes of human coronavirus (HCV) strain OC43 and bovine respiratory coronavirus (BRCV) strain G95 were determined from single-stranded cDNA fragments generated by reverse transcription of virus-specific mRNAs and amplified by polymerase chain reaction. Phylogenetic analysis suggests that the HE genes of coronaviruses and influenza C virus have a common ancestral origin, and that bovine coronaviruses and HCV-OC43 are closely related. We report here the complete nucleotide sequence of the HE genes of HCV-OC43 and BRCV-G95, and their phylogenetic relatedness to BCVs, MHV, and ICV. The predicted amino acid sequences of the HE genes from HCV-OC43 and BRCV-G95 (Fig. l) , BCVMost importantly, the putative acetylesterase active site (F-G-D-S) (at amino acids 72 to 75 in Fig. 2) is conserved in all HE proteins of human, bovine, and murine coronaviruses and ICV. abstract: Abstract The complete nucleotide sequences of the hemagglutinin/esterase (HE) genes of human coronavirus (HCV) strain OC43 and bovine respiratory coronavirus (BRCV) strain G95 were determined from single-stranded cDNA fragments generated by reverse transcription of virus-specific mRNAs and amplified by polymerase chain reaction. An open reading frame of 1272 nucleotides was identified as the putative HE gene by homology to the bovine coronavirus HE gene. This open reading frame encodes a protein of 424 amino acids with an estimated molecular weight of 47.7 kDa. Ten potential N-linked glycosylation sites were predicted in the HE protein of HCV-OC43 while nine of them were present in BRCV-G95. Fourteen cysteine residues were conserved in the HE proteins of both viruses. Two hydrophobic sequences at the N-terminus and the C-terminus may serve as signal peptide and transmembrane anchoring domain, respectively. The predicted HE protein of HCV-OC43 was 95% identical to the HEs of BRCV-G95 and other bovine coronaviruses, and 60% identical to the HEs of mouse hepatitis viruses. Phylogenetic analysis suggests that the HE genes of coronaviruses and influenza C virus have a common ancestral origin, and that bovine coronaviruses and HCV-OC43 are closely related. url: https://api.elsevier.com/content/article/pii/0042682292900898 doi: 10.1016/0042-6822(92)90089-8 id: cord-281941-97t45w73 author: Zhou, Daijun title: Cyclophilin A and viral infections date: 2012-08-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Cyclophilin A (CyPA) is a peptidyl-prolyl cis/trans isomerase originally identified as the target of the immunosuppressive drug cyclosporine A. A number of reports have demonstrated that CyPA plays a critical role in the successful replication of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), etc. However, recent studies demonstrated that CyPA also possesses a repressive effect on the replication of some viruses like Influenza A virus and rotavirus. Moreover, CyPA could also regulate host IFN-I response to viral infections. Together, these evidences showed diverse roles of CyPA in viral infection. url: https://doi.org/10.1016/j.bbrc.2012.07.024 doi: 10.1016/j.bbrc.2012.07.024 id: cord-284549-edliu3it author: Zhou, Hui title: Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells date: 2019-11-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RNAi interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism and has been well recognized as an important antiviral immunity in eukaryotes. Numerous viruses have been shown to encode viral suppressors of RNAi (VSRs) to antagonize antiviral RNAi. Hepatitis C virus (HCV) is a medically important human pathogen that causes acute and chronic hepatitis. In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. Moreover, we demonstrated that NS2 could suppress RNAi via its direct interaction with double-stranded RNAs (dsRNAs) and siRNAs, and further identified that the cysteine 184 of NS2 is required for the RNAi suppression activity through a serial of point mutation analyses. Together, our findings uncovered that HCV NS2 can act as a VSR in vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00182-5) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s12250-019-00182-5 doi: 10.1007/s12250-019-00182-5 id: cord-000083-3p81yr4n author: nan title: Poster Exhibition date: 2009-01-31 words: 112815.0 sentences: 7542.0 pages: flesch: 56.0 cache: ./cache/cord-000083-3p81yr4n.txt txt: ./txt/cord-000083-3p81yr4n.txt summary: R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712310/ doi: 10.1007/s12072-009-9123-4 id: cord-002774-tpqsjjet author: nan title: Section II: Poster Sessions date: 2017-12-01 words: 83515.0 sentences: 5162.0 pages: flesch: 54.0 cache: ./cache/cord-002774-tpqsjjet.txt txt: ./txt/cord-002774-tpqsjjet.txt summary: Results: The CHIP Framework The CHIP framework aims to improve the health and wellness of the urban communities served by St. Josephs Health Centre through four intersecting pillars: • Raising Community Voices provides an infrastructure and process that supports community stakeholder input into health care service planning, decision-making, and delivery by the hospital and across the continuum of care; • Sharing Reciprocal Capacity promotes healthy communities through the sharing of our intellectual and physical capacity with our community partners; • Cultivating Integration Initiatives facilitates vertical, horizontal, and intersectoral integration initiatives in support of community-identified needs and gaps; and • Facilitating Healthy Exchange develops best practices in community integration through community-based research, and facilitates community voice in informing public policy. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711696/ doi: 10.1093/jurban/jti137 id: cord-006856-b1w25ob5 author: nan title: 19th Meeting of the Austrian Society of Transplantation, Transfusion, and Genetics, October 26–28, 2005 date: 2005 words: 29625.0 sentences: 1983.0 pages: flesch: 52.0 cache: ./cache/cord-006856-b1w25ob5.txt txt: ./txt/cord-006856-b1w25ob5.txt summary: Egr-1 and hypoxia-inducible factor-1 (HIF-1) gene expression was examined in left ventricular biopsies of explanted failing hearts in 28 ICM and 42 DCM patients, as well as in 12 donor grafts before reperfusion (control), at 10, 30, 60 minutes after reperfusion, and at 1, 2, 3, 4, 6, 12 posttransplant weeks, using real-time RT-PCR. The risk of transplant-related mortality (TRM) due to graft-versushost disease (GvHD) is higher in male recipients of female stem cells compared with female patients receiving a graft from a female donor. We therefore analyzed a single-center cohort of 72 high-risk patients transplanted with a related or unrelated stem cell graft after nonmyeloablative conditioning for outcome (acute and chronic GvHD, TRM, relapse, and survival). Four patients between the age of 34 and 44 years underwent allogeneic peripheral blood stem cell (PBSC) transplantation (SCT) from HLA-identical sibling or unrelated donors at our institution. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103192/ doi: 10.1007/s10353-005-0216-6 id: cord-007890-bie1veti author: nan title: ECC-4 Abstracts date: 2002-04-16 words: 85992.0 sentences: 5665.0 pages: flesch: 50.0 cache: ./cache/cord-007890-bie1veti.txt txt: ./txt/cord-007890-bie1veti.txt summary: Effects of Interferon alpha plus ribavirine therapy on frequencies of HCV, HIV and CMV specific CD4-T-cell responses in peripheral blood of HIV/HCV coinfected patients after 6 months of treatment SoA9.5 Methods: Two groups of patients with chronic HCV infection were studied: 26 HIV coinfected progressors with antiretroviral therapy and 13 HIV-negative controls. In order to assess the local temporal trend of antibiotic sensitivity of the most common urinary tract bacterial pathogen, all urine-cultured Escherichia coli isolates were reviewed as to susceptibility profile, and specimen source (community-versus hospital-acquired infection). Methods: A total of 87 penicillin resistant clinical strains isolated from patients at Hacettepe Children''s Hospital, Ankara, Turkey between 1999 and 2001 were tested for their in vitro susceptibility to various antibiotics that are commonly used in the treatment of respiratory tract infections. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126403/ doi: 10.1016/s0924-8579(02)00033-x id: cord-009567-osstpum6 author: nan title: Abstracts Oral date: 2008-04-23 words: 131214.0 sentences: 7728.0 pages: flesch: 53.0 cache: ./cache/cord-009567-osstpum6.txt txt: ./txt/cord-009567-osstpum6.txt summary: Introduction: Previously, it has been demonstrated that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during cardiac rejection, suggesting infiltration of regulatory T cells in the transplanted organ during an allogeneic response. Efficacy and safety parameters assessed at follow-up included: acute rejection; patient and graft survival; renal function, vital signs, basic lab results and immunosuppressive regimen for the patients 10 years after completion of the original study. We analyzed, for the first time, the expression of TLR4 in PBMC from kidney recipients with contrasted situations: operational tolerance and chronic immune-mediated rejection (Banff 2005), compared to patients with normal histology and stable graft function, non transplant patients with renal failure and healthy volunteers. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159651/ doi: 10.1111/j.1600-6143.2008.02254.x id: cord-010088-s9tfvtao author: nan title: Oral Abstracts date: 2013-11-01 words: 43522.0 sentences: 2257.0 pages: flesch: 49.0 cache: ./cache/cord-010088-s9tfvtao.txt txt: ./txt/cord-010088-s9tfvtao.txt summary: These include ''incorrect blood component transfused'' events, where the blood component was intended for another recipient (frequently due to errors in patient identification at the time of collection of the pre-transfusion sample, or at the time of bedside administration), or did not meet the patient''s special needs (such as a patient with a red cell antibody who did not receive the required antigen-negative unit). Methods: Eligibility criteria for inclusion in the study included the following: transfusion of Rh D positive platelets, no anti D detectable before transfusion, no previous exposure to Rh D positive blood components, and results of follow-up testing of anti-D in patients serum available. In addition, the allelic frequency of Hpdel was calculated to be 0.015 by a genetic study of a limited number of the Japanese individuals, suggesting that Hp deficiency might distribute among the Japanese population as a phenotype of serum Hp. Aims: In this report, we present the results obtained from a hemovigilance survey carried out between 1998 and 2012, in which Hp deficiency was identified among Japanese patients who had experienced nonhemolytic TRs (NHTRs), and those obtained from a screening of Hp-deficient Japanese healthy blood donors. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169312/ doi: 10.1111/vox.12100_1 id: cord-010092-uftc8inx author: nan title: Abstract of 29th Regional Congress of the ISBT date: 2019-06-07 words: 233304.0 sentences: 13171.0 pages: flesch: 54.0 cache: ./cache/cord-010092-uftc8inx.txt txt: ./txt/cord-010092-uftc8inx.txt summary: Prospective testing of blood donations in endemic areas of the U.S. revealed 0.38% of donors were positive for Babesia DNA or antibodies (Moritz, NEJM, 2016) Aims: -To report results of ongoing Babesia clinical trial -To explain significance of Babesia as a TT infection Methods: In cobas â Babesia for use on the cobas â 6800/8800 Systems, is a qualitative polymerase chain reaction nucleic acid amplification test, developed to detect in whole blood (WB) donor samples the 4 Babesia species that cause human disease: B. In sensitivity analyses, there were two discrepant results for HIV testing, three for HCV, and five for anti-HBc. Summary/Conclusions: Elecsys â infectious disease parameters on the cobas e 801 analyser demonstrate high specificity/sensitivity for screening first-time blood donor samples, with similar clinical performance to other commercially available assays. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169345/ doi: 10.1111/vox.12792 id: cord-010119-t1x9gknd author: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 words: 230193.0 sentences: 13234.0 pages: flesch: 55.0 cache: ./cache/cord-010119-t1x9gknd.txt txt: ./txt/cord-010119-t1x9gknd.txt summary: Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/ doi: 10.1111/trf.14286 id: cord-015372-76xvzvdg author: nan title: National scientific medical meeting 1996 abstracts date: 1996 words: 36596.0 sentences: 2204.0 pages: flesch: 53.0 cache: ./cache/cord-015372-76xvzvdg.txt txt: ./txt/cord-015372-76xvzvdg.txt summary: One, two and five-year survival rates were examined; age at diagnosis and lesion type were extremely significant factors in relation to patient outcome. Patients'' age, sex, risk group, CDC stage, CD4 count, indication for therapy, complication rate and response to treatment are described. Fifty-eight patients (34 male, 24 female) ranging in age from 15 to 65 years (Mean + SD = 28.4 + 10.8) were included in the study. Among these 48 patients (mean age 68.0+12.7), after controlling for age and for the duration and continuity of subsequent antipsychotic treatment, increasing duration of initially untreated psychosis was associated with greater severity of negative symptoms (p<0.005) and with lower scores on the MMSE (p<0.05) but not with executive dysfunction on the EXIT (p=0.3). Conclusion Although not a population based study, care of IDDM in Ireland is almost totally hospital clinic based Cigarette smoking is identified as the major problem to be addressed Patients with diabetes meltitus (DM) are at a higher risk of developing vascular complications, including coronary artery disease (CAD). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103226/ doi: 10.1007/bf02945204 id: cord-020010-q58x6xb0 author: nan title: 19th ICAR Abstracts: date: 2006-03-13 words: 46663.0 sentences: 2181.0 pages: flesch: 44.0 cache: ./cache/cord-020010-q58x6xb0.txt txt: ./txt/cord-020010-q58x6xb0.txt summary: In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133865/ doi: 10.1016/j.antiviral.2006.02.001 id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 words: 188640.0 sentences: 9313.0 pages: flesch: 45.0 cache: ./cache/cord-022888-dnsdg04n.txt txt: ./txt/cord-022888-dnsdg04n.txt summary: Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. abstract: No Abtract url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/ doi: 10.1002/eji.200990224 id: cord-023017-k6edtg58 author: nan title: AASLD Abstracts (pp. 282A–382A) date: 2006-02-10 words: 65796.0 sentences: 3553.0 pages: flesch: 51.0 cache: ./cache/cord-023017-k6edtg58.txt txt: ./txt/cord-023017-k6edtg58.txt summary: 14/55 (25%) patients in AC who did not discontinue by week 24 received ribavirin dose reduction in comparison to 31/108 ( The clinical outcome in response to combination therapy for treatment of chronic hepatitis C virus (HCV) infection appears to be different for Caucasian versus African American patients. Over the period of combination therapy, most patients in which serum virus titers were reduced to non detectable levels had significant increases in T cell responses to HCV proteins. CHRONIC Background: Recent large prospective trials demonstrated that the combination therapy of interferon (1FN)-alphalribavirin significantly increased the ratio of a sustained virological response in patients with chronic hepatitis C in comparison with IFN monotherapy, especially in patients with high HCV-RNA titer and genotype lb. Results: Patients with chronic HCV infection showed higher MxA gene expression levels than healthy controls, indicating that hepatitis C virus induces IFN production. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165819/ doi: 10.1002/hep.1840380505 id: cord-023033-tgt69ir6 author: nan title: Poster Session (pp. 78A–178A) date: 2006-02-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165951/ doi: 10.1002/hep.1840380503 id: cord-023346-8sqbqjm1 author: nan title: MONDAY: POSTERS date: 2005-06-08 words: 130043.0 sentences: 7330.0 pages: flesch: 54.0 cache: ./cache/cord-023346-8sqbqjm1.txt txt: ./txt/cord-023346-8sqbqjm1.txt summary: • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169255/ doi: 10.1111/j.1423-0410.2005.00652.x id: cord-023354-f2ciho6o author: nan title: TUESDAY PLENARY SESSION 3 TUESDAY: POSTERS date: 2005-06-08 words: 130046.0 sentences: 7333.0 pages: flesch: 54.0 cache: ./cache/cord-023354-f2ciho6o.txt txt: ./txt/cord-023354-f2ciho6o.txt summary: • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169300/ doi: 10.1111/j.1423-0410.2005.00654.x id: cord-023364-ut56gczm author: nan title: EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS date: 2005-06-08 words: 130049.0 sentences: 7334.0 pages: flesch: 54.0 cache: ./cache/cord-023364-ut56gczm.txt txt: ./txt/cord-023364-ut56gczm.txt summary: • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169338/ doi: 10.1111/j.1423-0410.2005.00651.x id: cord-350571-6tapkjb6 author: nan title: 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016 date: 2017-01-10 words: 106013.0 sentences: 6203.0 pages: flesch: 48.0 cache: ./cache/cord-350571-6tapkjb6.txt txt: ./txt/cord-350571-6tapkjb6.txt summary: Possible solutions might be to use shared communication tools like Internet based communication programs and to introduce the patient as a participant at the IMRs. Please specify your abstract type: Research abstract Background and objective: International good pharmacy practice guidelines describe how pharmacists should counsel the patients about their medicines, offer additional services where needed, and intervene at drug related problems. Please specify your abstract type: Descriptive abstract (for projects) Background and objective: In order to improve the medication reconciliation and to implement training programs for the medical team in an associated to general hospital nursing (ASNH) home we measured the discrepancies between pharmacy registered treatments (PRT) and medical prescriptions (MP), and we analysed potentially inappropriate prescriptions according to ''''American Geriatrics Society 2015 Beers Criteria'''' and ''''STOPP-START 2014 criteria. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/28074393/ doi: 10.1007/s11096-016-0404-4 id: cord-289321-ahl46ql9 author: van Buuren, Nicholas title: Transmission genetics of drug-resistant hepatitis C virus date: 2018-03-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Antiviral development is plagued by drug resistance and genetic barriers to resistance are needed. For HIV and hepatitis C virus (HCV), combination therapy has proved life-saving. The targets of direct-acting antivirals for HCV infection are NS3/4A protease, NS5A phosphoprotein and NS5B polymerase. Differential visualization of drug-resistant and -susceptible RNA genomes within cells revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are cis-dominant, ensuring their direct selection from complex environments. Confocal microscopy revealed that RNA replication complexes are genome-specific, rationalizing the non-interaction of wild-type and variant products. No HCV antivirals yet display the dominance of drug susceptibility shown for capsid proteins of other viruses. However, effective inhibitors of HCV polymerase exact such high fitness costs for drug resistance that stable genome selection is not observed. Barriers to drug resistance vary with target biochemistry and detailed analysis of these barriers should lead to the use of fewer drugs. url: https://www.ncbi.nlm.nih.gov/pubmed/29589830/ doi: 10.7554/elife.32579 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel