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A title: The Scientific Response to a Pandemic date: 2006-02-24 journal: PLoS Pathog DOI: 10.1371/journal.ppat.0020009 sha: doc_id: 304815 cord_uid: 3datxv8j file: cache/cord-000103-3zh8jmc2.json key: cord-000103-3zh8jmc2 authors: Caignard, Grégory; Komarova, Anastassia V.; Bouraï, Mehdi; Mourez, Thomas; Jacob, Yves; Jones, Louis M.; Rozenberg, Flore; Vabret, Astrid; Freymuth, François; Tangy, Frédéric; Vidalain, Pierre-Olivier title: Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor date: 2009-09-18 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000587 sha: doc_id: 103 cord_uid: 3zh8jmc2 file: cache/cord-002835-qaogpxy9.json key: cord-002835-qaogpxy9 authors: Too, Issac Horng Khit; Bonne, Isabelle; Tan, Eng Lee; Chu, Justin Jang Hann; Alonso, Sylvie title: Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis date: 2018-01-11 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1006778 sha: doc_id: 2835 cord_uid: qaogpxy9 file: cache/cord-278511-je1509ar.json key: cord-278511-je1509ar authors: Wang, David title: 5 challenges in understanding the role of the virome in health and disease date: 2020-03-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008318 sha: doc_id: 278511 cord_uid: je1509ar file: cache/cord-287219-qxkwjkif.json key: cord-287219-qxkwjkif authors: Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.; Lewis, Mark G.; Geisbert, Joan B.; Grolla, Allen; Leung, Anders; Paragas, Jason; Matthias, Lennox; Smith, Mark A.; Jones, Steven M.; Hensley, Lisa E.; Feldmann, Heinz; Jahrling, Peter B. title: Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates date: 2008-11-28 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000225 sha: doc_id: 287219 cord_uid: qxkwjkif file: cache/cord-001769-2sdg5ll7.json key: cord-001769-2sdg5ll7 authors: Guo, Sheng; Yang, Chengying; Diao, Bo; Huang, Xiaoyong; Jin, Meihua; Chen, Lili; Yan, Weiming; Ning, Qin; Zheng, Lixin; Wu, Yuzhang; Chen, Yongwen title: The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis date: 2015-09-14 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005155 sha: doc_id: 1769 cord_uid: 2sdg5ll7 file: cache/cord-076082-4kpkhz0o.json key: cord-076082-4kpkhz0o authors: Lam, Tommy Tsan-Yuk; Hon, Chung-Chau; Pybus, Oliver G.; Kosakovsky Pond, Sergei L.; Wong, Raymond Tze-Yeung; Yip, Chi-Wai; Zeng, Fanya; Leung, Frederick Chi-Ching title: Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia date: 2008-08-22 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000130 sha: doc_id: 76082 cord_uid: 4kpkhz0o file: cache/cord-001676-68y733y3.json key: cord-001676-68y733y3 authors: Shoemaker, Jason E.; Fukuyama, Satoshi; Eisfeld, Amie J.; Zhao, Dongming; Kawakami, Eiryo; Sakabe, Saori; Maemura, Tadashi; Gorai, Takeo; Katsura, Hiroaki; Muramoto, Yukiko; Watanabe, Shinji; Watanabe, Tokiko; Fuji, Ken; Matsuoka, Yukiko; Kitano, Hiroaki; Kawaoka, Yoshihiro title: An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation date: 2015-06-05 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1004856 sha: doc_id: 1676 cord_uid: 68y733y3 file: cache/cord-253783-3a1qde41.json key: cord-253783-3a1qde41 authors: Johnson, Christopher J; Phillips, Kristen E; Schramm, Peter T; McKenzie, Debbie; Aiken, Judd M; Pedersen, Joel A title: Prions Adhere to Soil Minerals and Remain Infectious date: 2006-04-14 journal: PLoS Pathog DOI: 10.1371/journal.ppat.0020032 sha: doc_id: 253783 cord_uid: 3a1qde41 file: cache/cord-297702-vxcj25sn.json key: cord-297702-vxcj25sn authors: Chen, Yuxin; Tong, Xin; Li, Yang; Gu, Bin; Yan, Jiawei; Liu, Yong; Shen, Han; Huang, Rui; Wu, Chao title: A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients date: 2020-09-10 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008796 sha: doc_id: 297702 cord_uid: vxcj25sn file: cache/cord-000246-mlhd9zbs.json key: cord-000246-mlhd9zbs authors: Valkenburg, Sophie A.; Gras, Stephanie; Guillonneau, Carole; La Gruta, Nicole L.; Thomas, Paul G.; Purcell, Anthony W.; Rossjohn, Jamie; Doherty, Peter C.; Turner, Stephen J.; Kedzierska, Katherine title: Protective Efficacy of Cross-Reactive CD8(+) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold date: 2010-08-12 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1001039 sha: doc_id: 246 cord_uid: mlhd9zbs file: cache/cord-000354-05lnj3w0.json key: cord-000354-05lnj3w0 authors: de Vries, Erik; Tscherne, Donna M.; Wienholts, Marleen J.; Cobos-Jiménez, Viviana; Scholte, Florine; García-Sastre, Adolfo; Rottier, Peter J. 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M. title: Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus date: 2015-09-25 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005185 sha: doc_id: 263239 cord_uid: andje0wu file: cache/cord-310509-c8wp2m69.json key: cord-310509-c8wp2m69 authors: Morens, David M.; Fauci, Anthony S. title: Emerging Infectious Diseases: Threats to Human Health and Global Stability date: 2013-07-04 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003467 sha: doc_id: 310509 cord_uid: c8wp2m69 file: cache/cord-304747-ojyxs3cp.json key: cord-304747-ojyxs3cp authors: Gaynor, Anne M; Nissen, Michael D; Whiley, David M; Mackay, Ian M; Lambert, Stephen B; Wu, Guang; Brennan, Daniel C; Storch, Gregory A; Sloots, Theo P; Wang, David title: Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections date: 2007-05-04 journal: PLoS Pathog DOI: 10.1371/journal.ppat.0030064 sha: doc_id: 304747 cord_uid: ojyxs3cp file: cache/cord-303403-9th2jiq6.json key: cord-303403-9th2jiq6 authors: Qing, Jie; Wang, Yaxin; Sun, Yuna; Huang, Jiaoyan; Yan, Wenzhong; Wang, Jinglan; Su, Dan; Ni, Cheng; Li, Jian; Rao, Zihe; Liu, Lei; Lou, Zhiyong title: Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator date: 2014-10-02 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1004422 sha: doc_id: 303403 cord_uid: 9th2jiq6 file: cache/cord-264579-csro48ks.json key: cord-264579-csro48ks authors: Sigalov, Alexander B. title: Novel Mechanistic Insights into Viral Modulation of Immune Receptor Signaling date: 2009-07-31 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000404 sha: doc_id: 264579 cord_uid: csro48ks file: cache/cord-323568-s0wmll4q.json key: cord-323568-s0wmll4q authors: Shang, Jian; Zheng, Yuan; Yang, Yang; Liu, Chang; Geng, Qibin; Luo, Chuming; Zhang, Wei; Li, Fang title: Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins date: 2018-04-23 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1007009 sha: doc_id: 323568 cord_uid: s0wmll4q file: cache/cord-268677-ytxrrslz.json key: cord-268677-ytxrrslz authors: Züst, Roland; Dong, Hongping; Li, Xiao-Feng; Chang, David C.; Zhang, Bo; Balakrishnan, Thavamalar; Toh, Ying-Xiu; Jiang, Tao; Li, Shi-Hua; Deng, Yong-Qiang; Ellis, Brett R.; Ellis, Esther M.; Poidinger, Michael; Zolezzi, Francesca; Qin, Cheng-Feng; Shi, Pei-Yong; Fink, Katja title: Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques date: 2013-08-01 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003521 sha: doc_id: 268677 cord_uid: ytxrrslz file: cache/cord-325326-2bbqz4o7.json key: cord-325326-2bbqz4o7 authors: Beitzel, Brett F.; Bakken, Russell R.; Smith, Jeffrey M.; Schmaljohn, Connie S. title: High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing date: 2010-10-14 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1001146 sha: doc_id: 325326 cord_uid: 2bbqz4o7 file: cache/cord-325624-6anybxnk.json key: cord-325624-6anybxnk authors: Ireland, Derek D. C.; Stohlman, Stephen A.; Hinton, David R.; Kapil, Parul; Silverman, Robert H.; Atkinson, Roscoe A.; Bergmann, Cornelia C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000602 sha: doc_id: 325624 cord_uid: 6anybxnk file: cache/cord-325825-0lyt8gfq.json key: cord-325825-0lyt8gfq authors: Griffiths, Samantha J.; Koegl, Manfred; Boutell, Chris; Zenner, Helen L.; Crump, Colin M.; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C.; Barry, Gerald; Martin, Kim; Craigon, Marie H.; Chen, Rui; Kaza, Lakshmi N.; Fossum, Even; Fazakerley, John K.; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003514 sha: doc_id: 325825 cord_uid: 0lyt8gfq file: cache/cord-325192-italbsed.json key: cord-325192-italbsed authors: Desai, Tanay M.; Marin, Mariana; Chin, Christopher R.; Savidis, George; Brass, Abraham L.; Melikyan, Gregory B. title: IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion date: 2014-04-03 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1004048 sha: doc_id: 325192 cord_uid: italbsed file: cache/cord-324928-cpryxa6p.json key: cord-324928-cpryxa6p authors: Lello, Laura Sandra; Utt, Age; Bartholomeeusen, Koen; Wang, Sainan; Rausalu, Kai; Kendall, Catherine; Coppens, Sandra; Fragkoudis, Rennos; Tuplin, Andrew; Alphey, Luke; Ariën, Kevin K.; Merits, Andres title: Cross-utilisation of template RNAs by alphavirus replicases date: 2020-09-04 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008825 sha: doc_id: 324928 cord_uid: cpryxa6p file: cache/cord-331721-l5kocy4f.json key: cord-331721-l5kocy4f authors: Liang, Jingjing; Sagum, Cari A.; Bedford, Mark T.; Sidhu, Sachdev S.; Sudol, Marius; Han, Ziying; Harty, Ronald N. title: Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress date: 2017-01-11 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1006132 sha: doc_id: 331721 cord_uid: l5kocy4f file: cache/cord-331802-wo462anq.json key: cord-331802-wo462anq authors: Xia, Hongjie; Wang, Peipei; Wang, Guang-Chuan; Yang, Jie; Sun, Xianlin; Wu, Wenzhe; Qiu, Yang; Shu, Ting; Zhao, Xiaolu; Yin, Lei; Qin, Cheng-Feng; Hu, Yuanyang; Zhou, Xi title: Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone date: 2015-07-28 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005067 sha: doc_id: 331802 cord_uid: wo462anq file: cache/cord-338053-8zlxsf1z.json key: cord-338053-8zlxsf1z authors: Foo, Suan-Sin; Chen, Weiqiang; Taylor, Adam; Sheng, Kuo-Ching; Yu, Xing; Teng, Terk-Shin; Reading, Patrick C.; Blanchard, Helen; Garlanda, Cecilia; Mantovani, Alberto; Ng, Lisa F. P.; Herrero, Lara J.; Mahalingam, Suresh title: Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation date: 2015-02-19 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1004649 sha: doc_id: 338053 cord_uid: 8zlxsf1z file: cache/cord-332205-ydijp66b.json key: cord-332205-ydijp66b authors: Hufsky, Franziska; Ibrahim, Bashar; Beer, Martin; Deng, Li; Mercier, Philippe Le; McMahon, Dino P.; Palmarini, Massimo; Thiel, Volker; Marz, Manja title: Virologists—Heroes need weapons date: 2018-02-08 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1006771 sha: doc_id: 332205 cord_uid: ydijp66b file: cache/cord-328947-3l9ydspz.json key: cord-328947-3l9ydspz authors: Webb, L. G.; Veloz, J.; Pintado-Silva, J.; Zhu, T.; Rangel, M. V.; Mutetwa, T.; Zhang, L.; Bernal-Rubio, D.; Figueroa, D.; Carrau, L.; Fenutria, R.; Potla, U.; Reid, St. P.; Yount, J. S.; Stapleford, K. A.; Aguirre, S.; Fernandez-Sesma, A. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008999 sha: doc_id: 328947 cord_uid: 3l9ydspz file: cache/cord-332747-u46xryoo.json key: cord-332747-u46xryoo authors: Mingorance, Lidia; Castro, Victoria; Ávila-Pérez, Ginés; Calvo, Gema; Rodriguez, María Josefa; Carrascosa, José L.; Pérez-del-Pulgar, Sofía; Forns, Xavier; Gastaminza, Pablo title: Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation date: 2018-09-18 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1007284 sha: doc_id: 332747 cord_uid: u46xryoo file: cache/cord-334315-ymkrgj0h.json key: cord-334315-ymkrgj0h authors: Moon, Stephanie L.; Wilusz, Jeffrey title: Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine date: 2013-12-05 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003762 sha: doc_id: 334315 cord_uid: ymkrgj0h file: cache/cord-341034-2oigu75k.json key: cord-341034-2oigu75k authors: Moser, Theresa S.; Schieffer, Daniel; Cherry, Sara title: AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis date: 2012-04-19 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1002661 sha: doc_id: 341034 cord_uid: 2oigu75k file: cache/cord-342291-imn7g084.json key: cord-342291-imn7g084 authors: Ciminski, Kevin; Pfaff, Florian; Beer, Martin; Schwemmle, Martin title: Bats reveal the true power of influenza A virus adaptability date: 2020-04-16 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008384 sha: doc_id: 342291 cord_uid: imn7g084 file: cache/cord-333473-c1lykari.json key: cord-333473-c1lykari authors: Irigoyen, Nerea; Firth, Andrew E.; Jones, Joshua D.; Chung, Betty Y.-W.; Siddell, Stuart G.; Brierley, Ian title: High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling date: 2016-02-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005473 sha: doc_id: 333473 cord_uid: c1lykari file: cache/cord-338400-30vl2hks.json key: cord-338400-30vl2hks authors: Epstein, Jonathan H.; Quan, Phenix-Lan; Briese, Thomas; Street, Craig; Jabado, Omar; Conlan, Sean; Ali Khan, Shahneaz; Verdugo, Dawn; Hossain, M. Jahangir; Hutchison, Stephen K.; Egholm, Michael; Luby, Stephen P.; Daszak, Peter; Lipkin, W. Ian title: Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh date: 2010-07-01 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000972 sha: doc_id: 338400 cord_uid: 30vl2hks file: cache/cord-348799-qu4zin3o.json key: cord-348799-qu4zin3o authors: Wu, Nannan; Nguyen, Xuan-Nhi; Wang, Li; Appourchaux, Romain; Zhang, Chengfei; Panthu, Baptiste; Gruffat, Henri; Journo, Chloé; Alais, Sandrine; Qin, Juliang; Zhang, Na; Tartour, Kevin; Catez, Frédéric; Mahieux, Renaud; Ohlmann, Theophile; Liu, Mingyao; Du, Bing; Cimarelli, Andrea title: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation date: 2019-10-10 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008093 sha: doc_id: 348799 cord_uid: qu4zin3o file: cache/cord-342825-s8ddek2f.json key: cord-342825-s8ddek2f authors: Kim, Ye Ji; Kim, Eui Tae; Kim, Young-Eui; Lee, Myoung Kyu; Kwon, Ki Mun; Kim, Keun Il; Stamminger, Thomas; Ahn, Jin-Hyun title: Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators date: 2016-08-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005850 sha: doc_id: 342825 cord_uid: s8ddek2f file: cache/cord-355610-7xy4s483.json key: cord-355610-7xy4s483 authors: Hu, Dan; Zhu, Zhongyu; Li, Shun; Deng, Yongqiang; Wu, Yanling; Zhang, Nana; Puri, Vinita; Wang, Chunyu; Zou, Peng; Lei, Cheng; Tian, Xiaolong; Wang, Yulu; Zhao, Qi; Li, Wei; Prabakaran, Ponraj; Feng, Yang; Cardosa, Jane; Qin, Chengfeng; Zhou, Xiaohui; Dimitrov, Dimiter S.; Ying, Tianlei title: A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III date: 2019-06-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1007836 sha: doc_id: 355610 cord_uid: 7xy4s483 file: cache/cord-351952-lhhjax3s.json key: cord-351952-lhhjax3s authors: Pickering, Suzanne; Betancor, Gilberto; Galão, Rui Pedro; Merrick, Blair; Signell, Adrian W.; Wilson, Harry D.; Kia Ik, Mark Tan; Seow, Jeffrey; Graham, Carl; Acors, Sam; Kouphou, Neophytos; Steel, Kathryn J. A.; Hemmings, Oliver; Patel, Amita; Nebbia, Gaia; Douthwaite, Sam; O’Connell, Lorcan; Luptak, Jakub; McCoy, Laura E.; Brouwer, Philip; van Gils, Marit J.; Sanders, Rogier W.; Martinez Nunez, Rocio; Bisnauthsing, Karen; O’Hara, Geraldine; MacMahon, Eithne; Batra, Rahul; Malim, Michael H.; Neil, Stuart J. D.; Doores, Katie J.; Edgeworth, Jonathan D. title: Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings date: 2020-09-24 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008817 sha: doc_id: 351952 cord_uid: lhhjax3s file: cache/cord-353353-njvalb44.json key: cord-353353-njvalb44 authors: Lau, Susanna K. P.; Woo, Patrick C. Y.; Li, Kenneth S. M.; Zhang, Hao-Ji; Fan, Rachel Y. Y.; Zhang, Anna J. X.; Chan, Brandon C. C.; Lam, Carol S. F.; Yip, Cyril C. Y.; Yuen, Ming-Chi; Chan, Kwok-Hung; Chen, Zhi-Wei; Yuen, Kwok-Yung title: Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model date: 2016-10-13 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005911 sha: doc_id: 353353 cord_uid: njvalb44 file: cache/cord-343221-e29of29o.json key: cord-343221-e29of29o authors: Kindler, Eveline; Gil-Cruz, Cristina; Spanier, Julia; Li, Yize; Wilhelm, Jochen; Rabouw, Huib H.; Züst, Roland; Hwang, Mihyun; V’kovski, Philip; Stalder, Hanspeter; Marti, Sabrina; Habjan, Matthias; Cervantes-Barragan, Luisa; Elliot, Ruth; Karl, Nadja; Gaughan, Christina; van Kuppeveld, Frank J. M.; Silverman, Robert H.; Keller, Markus; Ludewig, Burkhard; Bergmann, Cornelia C.; Ziebuhr, John; Weiss, Susan R.; Kalinke, Ulrich; Thiel, Volker title: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date: 2017-02-03 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1006195 sha: doc_id: 343221 cord_uid: e29of29o file: cache/cord-351548-jvl63652.json key: cord-351548-jvl63652 authors: Juranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne title: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date: 2013-09-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003611 sha: doc_id: 351548 cord_uid: jvl63652 file: cache/cord-353337-o302vxqm.json key: cord-353337-o302vxqm authors: Visser, Linda J.; Aloise, Chiara; Swatek, Kirby N.; Medina, Gisselle N.; Olek, Karin M.; Rabouw, Huib H.; de Groot, Raoul J.; Langereis, Martijn A.; de los Santos, Teresa; Komander, David; Skern, Tim; van Kuppeveld, Frank J. M. title: Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date: 2020-07-15 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008702 sha: doc_id: 353337 cord_uid: o302vxqm file: cache/cord-353703-u86ggw11.json key: cord-353703-u86ggw11 authors: Gao, Peng; Chai, Yue; Song, Jiangwei; Liu, Teng; Chen, Peng; Zhou, Lei; Ge, Xinna; Guo, Xin; Han, Jun; Yang, Hanchun title: Reprogramming the unfolded protein response for replication by porcine reproductive and respiratory syndrome virus date: 2019-11-18 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008169 sha: doc_id: 353703 cord_uid: u86ggw11 file: cache/cord-334947-pa0p5dif.json key: cord-334947-pa0p5dif authors: Rozen-Gagnon, Kathryn; Stapleford, Kenneth A.; Mongelli, Vanesa; Blanc, Hervé; Failloux, Anna-Bella; Saleh, Maria-Carla; Vignuzzi, Marco title: Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models date: 2014-01-16 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003877 sha: doc_id: 334947 cord_uid: pa0p5dif file: cache/cord-351389-48tszqh5.json key: cord-351389-48tszqh5 authors: Xu, Kai; Rockx, Barry; Xie, Yihu; DeBuysscher, Blair L.; Fusco, Deborah L.; Zhu, Zhongyu; Chan, Yee-Peng; Xu, Yan; Luu, Truong; Cer, Regina Z.; Feldmann, Heinz; Mokashi, Vishwesh; Dimitrov, Dimiter S.; Bishop-Lilly, Kimberly A.; Broder, Christopher C.; Nikolov, Dimitar B. title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody date: 2013-10-10 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003684 sha: doc_id: 351389 cord_uid: 48tszqh5 file: cache/cord-350640-sz6xj5o3.json key: cord-350640-sz6xj5o3 authors: Menzel, Nicolas; Fischl, Wolfgang; Hueging, Kathrin; Bankwitz, Dorothea; Frentzen, Anne; Haid, Sibylle; Gentzsch, Juliane; Kaderali, Lars; Bartenschlager, Ralf; Pietschmann, Thomas title: MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles date: 2012-07-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1002829 sha: doc_id: 350640 cord_uid: sz6xj5o3 file: cache/cord-355839-o0m71kvw.json key: cord-355839-o0m71kvw authors: Sedeyn, Koen; Schepens, Bert; Saelens, Xavier title: Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date: 2019-10-17 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1007984 sha: doc_id: 355839 cord_uid: o0m71kvw file: cache/cord-356115-vblgotjn.json key: cord-356115-vblgotjn authors: Sawicki, Stanley G; Sawicki, Dorothea L; Younker, Diane; Meyer, Yvonne; Thiel, Volker; Stokes, Helen; Siddell, Stuart G title: Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins date: 2005-12-09 journal: PLoS Pathog DOI: 10.1371/journal.ppat.0010039 sha: doc_id: 356115 cord_uid: vblgotjn file: cache/cord-346053-mk1mzc5z.json key: cord-346053-mk1mzc5z authors: Morris, Cindy E.; Bardin, Marc; Kinkel, Linda L.; Moury, Benoit; Nicot, Philippe C.; Sands, David C. title: Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries date: 2009-12-24 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000693 sha: doc_id: 346053 cord_uid: mk1mzc5z file: cache/cord-342419-liaihahj.json key: cord-342419-liaihahj authors: Huang, Jiachen; Diaz, Darren; Mousa, Jarrod J. title: Antibody recognition of the Pneumovirus fusion protein trimer interface date: 2020-10-09 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008942 sha: doc_id: 342419 cord_uid: liaihahj Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-plosPathog-cord === 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: 89346 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: 90046 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: 90090 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: 90209 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: 89144 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: 89945 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: 89795 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: 90034 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: 90106 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: 90042 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: 89691 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: 90012 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: 90127 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: 89944 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: 90066 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: 89957 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: 90128 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: 90140 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: 90082 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: 90142 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: 90212 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: 89870 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: 90067 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: 90110 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. 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: 90007 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: 90070 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: 89875 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: 90194 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: 90096 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. 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: 90032 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: 90052 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: 90095 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: 90017 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: 90101 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: 90172 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: 90207 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: 90164 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: 89990 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: 90080 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: 90144 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: 90150 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: 90006 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: 90085 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: 90077 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: 90027 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: 90057 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: 89967 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: 90088 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: 89989 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: 90159 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: 90296 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: 90145 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: 89861 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: 90186 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-000127-tkxpjlyn author: Dermody, Terence S. title: Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity date: 2009-11-26 pages: extension: .txt txt: ./txt/cord-000127-tkxpjlyn.txt cache: ./cache/cord-000127-tkxpjlyn.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-000127-tkxpjlyn.txt' === file2bib.sh === id: cord-262248-q5eijunp author: Casadevall, Arturo title: The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases date: 2015-04-23 pages: extension: .txt txt: ./txt/cord-262248-q5eijunp.txt cache: ./cache/cord-262248-q5eijunp.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 2 resourceName b'cord-262248-q5eijunp.txt' === file2bib.sh === id: cord-312743-9e4yufo5 author: Breiman, Adrien title: Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2 date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-312743-9e4yufo5.txt cache: ./cache/cord-312743-9e4yufo5.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-312743-9e4yufo5.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 2 resourceName b'cord-258234-qn8xp4v9.txt' === file2bib.sh === id: cord-304815-3datxv8j author: Gronvall, Gigi Kwik title: The Scientific Response to a Pandemic date: 2006-02-24 pages: extension: .txt txt: ./txt/cord-304815-3datxv8j.txt cache: ./cache/cord-304815-3datxv8j.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-304815-3datxv8j.txt' === file2bib.sh === id: cord-278511-je1509ar author: Wang, David title: 5 challenges in understanding the role of the virome in health and disease date: 2020-03-26 pages: extension: .txt txt: ./txt/cord-278511-je1509ar.txt cache: ./cache/cord-278511-je1509ar.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 2 resourceName b'cord-278511-je1509ar.txt' === file2bib.sh === id: cord-268388-kkhuzf3p author: Sharif-Yakan, Ahmad title: Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date: 2014-12-04 pages: extension: .txt txt: ./txt/cord-268388-kkhuzf3p.txt cache: ./cache/cord-268388-kkhuzf3p.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-268388-kkhuzf3p.txt' === file2bib.sh === id: cord-000729-iq30z094 author: Marsh, Glenn A. title: Cedar Virus: A Novel Henipavirus Isolated from Australian Bats date: 2012-08-02 pages: extension: .txt txt: ./txt/cord-000729-iq30z094.txt cache: ./cache/cord-000729-iq30z094.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-000729-iq30z094.txt' === file2bib.sh === id: cord-001109-xs7df6a7 author: Tapia, Karla title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity date: 2013-10-31 pages: extension: .txt txt: ./txt/cord-001109-xs7df6a7.txt cache: ./cache/cord-001109-xs7df6a7.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-001109-xs7df6a7.txt' === file2bib.sh === id: cord-000409-lpf9lpky author: Chen, Yongwen title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date: 2011-07-07 pages: extension: .txt txt: ./txt/cord-000409-lpf9lpky.txt cache: ./cache/cord-000409-lpf9lpky.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-000409-lpf9lpky.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: 95591 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: 95300 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: 95495 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002893-d7hetoq0 author: Meng, Xiangzhi title: A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection date: 2018-02-15 pages: extension: .txt txt: ./txt/cord-002893-d7hetoq0.txt cache: ./cache/cord-002893-d7hetoq0.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-002893-d7hetoq0.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: 95319 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes 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: 95995 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: 95582 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes 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: 96091 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-297702-vxcj25sn author: Chen, Yuxin title: A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-297702-vxcj25sn.txt cache: ./cache/cord-297702-vxcj25sn.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-297702-vxcj25sn.txt' === file2bib.sh === id: cord-280621-tph5n7ak author: Kim, Yunjeong title: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor date: 2016-03-30 pages: extension: .txt txt: ./txt/cord-280621-tph5n7ak.txt cache: ./cache/cord-280621-tph5n7ak.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-280621-tph5n7ak.txt' === file2bib.sh === id: cord-000025-6zrv687k author: Chachu, Karen A. title: Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection date: 2008-12-12 pages: extension: .txt txt: ./txt/cord-000025-6zrv687k.txt cache: ./cache/cord-000025-6zrv687k.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 2 resourceName b'cord-000025-6zrv687k.txt' === file2bib.sh === id: cord-000318-wk2u2a9w author: Lamb, Daniel title: Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins date: 2011-02-03 pages: extension: .txt txt: ./txt/cord-000318-wk2u2a9w.txt cache: ./cache/cord-000318-wk2u2a9w.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-000318-wk2u2a9w.txt' === file2bib.sh === id: cord-000007-h8upyzb1 author: Butler, Noah S. title: Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant date: 2008-10-24 pages: extension: .txt txt: ./txt/cord-000007-h8upyzb1.txt cache: ./cache/cord-000007-h8upyzb1.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-000007-h8upyzb1.txt' === file2bib.sh === id: cord-000018-amvlm09p author: Pauli, Eva-K. title: Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression date: 2008-11-07 pages: extension: .txt txt: ./txt/cord-000018-amvlm09p.txt cache: ./cache/cord-000018-amvlm09p.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-000018-amvlm09p.txt' === file2bib.sh === id: cord-001700-c6elsnag author: Fusco, Marnie L. title: Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs date: 2015-06-26 pages: extension: .txt txt: ./txt/cord-001700-c6elsnag.txt cache: ./cache/cord-001700-c6elsnag.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-001700-c6elsnag.txt' === file2bib.sh === id: cord-287219-qxkwjkif author: Geisbert, Thomas W. title: Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates date: 2008-11-28 pages: extension: .txt txt: ./txt/cord-287219-qxkwjkif.txt cache: ./cache/cord-287219-qxkwjkif.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-287219-qxkwjkif.txt' === file2bib.sh === id: cord-253783-3a1qde41 author: Johnson, Christopher J title: Prions Adhere to Soil Minerals and Remain Infectious date: 2006-04-14 pages: extension: .txt txt: ./txt/cord-253783-3a1qde41.txt cache: ./cache/cord-253783-3a1qde41.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-253783-3a1qde41.txt' === file2bib.sh === id: cord-000005-zt6i3o86 author: Bischof, Larry J. title: Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo date: 2008-10-10 pages: extension: .txt txt: ./txt/cord-000005-zt6i3o86.txt cache: ./cache/cord-000005-zt6i3o86.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 291 resourceName b'cord-000005-zt6i3o86.txt' === file2bib.sh === id: cord-001636-khrx6rnh author: Bordería, Antonio V. title: Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype date: 2015-05-05 pages: extension: .txt txt: ./txt/cord-001636-khrx6rnh.txt cache: ./cache/cord-001636-khrx6rnh.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-001636-khrx6rnh.txt' === file2bib.sh === id: cord-000164-094d0rn6 author: Suthar, Mehul S. title: IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity date: 2010-02-05 pages: extension: .txt txt: ./txt/cord-000164-094d0rn6.txt cache: ./cache/cord-000164-094d0rn6.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-000164-094d0rn6.txt' === file2bib.sh === id: cord-002423-1u44tdrj author: Geoghegan, Jemma L. title: Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families date: 2017-02-08 pages: extension: .txt txt: ./txt/cord-002423-1u44tdrj.txt cache: ./cache/cord-002423-1u44tdrj.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-002423-1u44tdrj.txt' === file2bib.sh === id: cord-004428-ob5igsv5 author: Kizziah, James L. title: Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage date: 2020-02-18 pages: extension: .txt txt: ./txt/cord-004428-ob5igsv5.txt cache: ./cache/cord-004428-ob5igsv5.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-004428-ob5igsv5.txt' === file2bib.sh === id: cord-332205-ydijp66b author: Hufsky, Franziska title: Virologists—Heroes need weapons date: 2018-02-08 pages: extension: .txt txt: ./txt/cord-332205-ydijp66b.txt cache: ./cache/cord-332205-ydijp66b.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-332205-ydijp66b.txt' === file2bib.sh === id: cord-000232-boto4h8x author: Danthi, Pranav title: Bid Regulates the Pathogenesis of Neurotropic Reovirus date: 2010-07-01 pages: extension: .txt txt: ./txt/cord-000232-boto4h8x.txt cache: ./cache/cord-000232-boto4h8x.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 6 resourceName b'cord-000232-boto4h8x.txt' === file2bib.sh === id: cord-001541-5d64esp4 author: Walker, Peter J. title: Evolution of Genome Size and Complexity in the Rhabdoviridae date: 2015-02-13 pages: extension: .txt txt: ./txt/cord-001541-5d64esp4.txt cache: ./cache/cord-001541-5d64esp4.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-001541-5d64esp4.txt' === file2bib.sh === id: cord-003982-7v5xl1s3 author: Trus, Ivan title: Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring date: 2019-11-14 pages: extension: .txt txt: ./txt/cord-003982-7v5xl1s3.txt cache: ./cache/cord-003982-7v5xl1s3.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-003982-7v5xl1s3.txt' === file2bib.sh === id: cord-334315-ymkrgj0h author: Moon, Stephanie L. title: Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine date: 2013-12-05 pages: extension: .txt txt: ./txt/cord-334315-ymkrgj0h.txt cache: ./cache/cord-334315-ymkrgj0h.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-334315-ymkrgj0h.txt' === file2bib.sh === id: cord-342291-imn7g084 author: Ciminski, Kevin title: Bats reveal the true power of influenza A virus adaptability date: 2020-04-16 pages: extension: .txt txt: ./txt/cord-342291-imn7g084.txt cache: ./cache/cord-342291-imn7g084.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-342291-imn7g084.txt' === file2bib.sh === id: cord-269466-9hnal9ad author: Agbeci, Maxime title: Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus date: 2013-10-03 pages: extension: .txt txt: ./txt/cord-269466-9hnal9ad.txt cache: ./cache/cord-269466-9hnal9ad.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-269466-9hnal9ad.txt' === file2bib.sh === id: cord-000933-nn9gj0z1 author: Krzyzaniak, Magdalena Anna title: Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein date: 2013-04-11 pages: extension: .txt txt: ./txt/cord-000933-nn9gj0z1.txt cache: ./cache/cord-000933-nn9gj0z1.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-000933-nn9gj0z1.txt' === file2bib.sh === id: cord-290617-45be6gxe author: Poulain, Florian title: Footprint of the host restriction factors APOBEC3 on the genome of human viruses date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-290617-45be6gxe.txt cache: ./cache/cord-290617-45be6gxe.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-290617-45be6gxe.txt' === file2bib.sh === id: cord-266078-h53zpjab author: McGuckin Wuertz, Kathryn title: STING is required for host defense against neuropathological West Nile virus infection date: 2019-08-15 pages: extension: .txt txt: ./txt/cord-266078-h53zpjab.txt cache: ./cache/cord-266078-h53zpjab.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-266078-h53zpjab.txt' === file2bib.sh === id: cord-281404-5a8au32c author: Gastaldello, Stefano title: Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date: 2013-10-10 pages: extension: .txt txt: ./txt/cord-281404-5a8au32c.txt cache: ./cache/cord-281404-5a8au32c.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-281404-5a8au32c.txt' === file2bib.sh === id: cord-265947-7j9qqi8w author: Du, Wenjuan title: The 2(nd) sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance date: 2019-06-10 pages: extension: .txt txt: ./txt/cord-265947-7j9qqi8w.txt cache: ./cache/cord-265947-7j9qqi8w.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-265947-7j9qqi8w.txt' === file2bib.sh === id: cord-001257-t21l6i3f author: Kovalev, Nikolay title: The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication date: 2014-04-17 pages: extension: .txt txt: ./txt/cord-001257-t21l6i3f.txt cache: ./cache/cord-001257-t21l6i3f.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-001257-t21l6i3f.txt' === file2bib.sh === id: cord-002125-anp238gu author: Effantin, Grégory title: Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture date: 2016-07-11 pages: extension: .txt txt: ./txt/cord-002125-anp238gu.txt cache: ./cache/cord-002125-anp238gu.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-002125-anp238gu.txt' === file2bib.sh === id: cord-355610-7xy4s483 author: Hu, Dan title: A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III date: 2019-06-26 pages: extension: .txt txt: ./txt/cord-355610-7xy4s483.txt cache: ./cache/cord-355610-7xy4s483.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-355610-7xy4s483.txt' === file2bib.sh === id: cord-338400-30vl2hks author: Epstein, Jonathan H. title: Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh date: 2010-07-01 pages: extension: .txt txt: ./txt/cord-338400-30vl2hks.txt cache: ./cache/cord-338400-30vl2hks.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-338400-30vl2hks.txt' === file2bib.sh === id: cord-003441-810r5q03 author: Dzimianski, John V. title: Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity date: 2019-01-10 pages: extension: .txt txt: ./txt/cord-003441-810r5q03.txt cache: ./cache/cord-003441-810r5q03.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-003441-810r5q03.txt' === file2bib.sh === id: cord-346053-mk1mzc5z author: Morris, Cindy E. title: Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries date: 2009-12-24 pages: extension: .txt txt: ./txt/cord-346053-mk1mzc5z.txt cache: ./cache/cord-346053-mk1mzc5z.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-346053-mk1mzc5z.txt' === file2bib.sh === id: cord-260949-w2xuf15h author: Galluzzi, Lorenzo title: Viral Control of Mitochondrial Apoptosis date: 2008-05-30 pages: extension: .txt txt: ./txt/cord-260949-w2xuf15h.txt cache: ./cache/cord-260949-w2xuf15h.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-260949-w2xuf15h.txt' === file2bib.sh === id: cord-314451-mqnqjn0c author: Roberts, Anjeanette title: A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date: 2007-01-12 pages: extension: .txt txt: ./txt/cord-314451-mqnqjn0c.txt cache: ./cache/cord-314451-mqnqjn0c.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-314451-mqnqjn0c.txt' === file2bib.sh === id: cord-002542-f7l4ty2j author: Jaworski, Elizabeth title: Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus date: 2017-05-05 pages: extension: .txt txt: ./txt/cord-002542-f7l4ty2j.txt cache: ./cache/cord-002542-f7l4ty2j.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-002542-f7l4ty2j.txt' === file2bib.sh === id: cord-331721-l5kocy4f author: Liang, Jingjing title: Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress date: 2017-01-11 pages: extension: .txt txt: ./txt/cord-331721-l5kocy4f.txt cache: ./cache/cord-331721-l5kocy4f.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-331721-l5kocy4f.txt' === file2bib.sh === id: cord-351389-48tszqh5 author: Xu, Kai title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody date: 2013-10-10 pages: extension: .txt txt: ./txt/cord-351389-48tszqh5.txt cache: ./cache/cord-351389-48tszqh5.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-351389-48tszqh5.txt' === file2bib.sh === id: cord-353353-njvalb44 author: Lau, Susanna K. P. title: Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model date: 2016-10-13 pages: extension: .txt txt: ./txt/cord-353353-njvalb44.txt cache: ./cache/cord-353353-njvalb44.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-353353-njvalb44.txt' === file2bib.sh === id: cord-325326-2bbqz4o7 author: Beitzel, Brett F. title: High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing date: 2010-10-14 pages: extension: .txt txt: ./txt/cord-325326-2bbqz4o7.txt cache: ./cache/cord-325326-2bbqz4o7.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-325326-2bbqz4o7.txt' === file2bib.sh === id: cord-268677-ytxrrslz author: Züst, Roland title: Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques date: 2013-08-01 pages: extension: .txt txt: ./txt/cord-268677-ytxrrslz.txt cache: ./cache/cord-268677-ytxrrslz.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-268677-ytxrrslz.txt' === file2bib.sh === id: cord-355839-o0m71kvw author: Sedeyn, Koen title: Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date: 2019-10-17 pages: extension: .txt txt: ./txt/cord-355839-o0m71kvw.txt cache: ./cache/cord-355839-o0m71kvw.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-355839-o0m71kvw.txt' === file2bib.sh === id: cord-001992-m4k20i7g author: Ziegler, Christopher M. title: The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles date: 2016-03-24 pages: extension: .txt txt: ./txt/cord-001992-m4k20i7g.txt cache: ./cache/cord-001992-m4k20i7g.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-001992-m4k20i7g.txt' === file2bib.sh === id: cord-325624-6anybxnk author: Ireland, Derek D. C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 pages: extension: .txt txt: ./txt/cord-325624-6anybxnk.txt cache: ./cache/cord-325624-6anybxnk.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-325624-6anybxnk.txt' === file2bib.sh === id: cord-331802-wo462anq author: Xia, Hongjie title: Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone date: 2015-07-28 pages: extension: .txt txt: ./txt/cord-331802-wo462anq.txt cache: ./cache/cord-331802-wo462anq.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-331802-wo462anq.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-343221-e29of29o author: Kindler, Eveline title: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date: 2017-02-03 pages: extension: .txt txt: ./txt/cord-343221-e29of29o.txt cache: ./cache/cord-343221-e29of29o.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-343221-e29of29o.txt' === file2bib.sh === id: cord-325192-italbsed author: Desai, Tanay M. title: IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion date: 2014-04-03 pages: extension: .txt txt: ./txt/cord-325192-italbsed.txt cache: ./cache/cord-325192-italbsed.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-325192-italbsed.txt' === file2bib.sh === id: cord-334947-pa0p5dif author: Rozen-Gagnon, Kathryn title: Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models date: 2014-01-16 pages: extension: .txt txt: ./txt/cord-334947-pa0p5dif.txt cache: ./cache/cord-334947-pa0p5dif.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-334947-pa0p5dif.txt' === file2bib.sh === id: cord-353337-o302vxqm author: Visser, Linda J. title: Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-353337-o302vxqm.txt cache: ./cache/cord-353337-o302vxqm.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-353337-o302vxqm.txt' === file2bib.sh === id: cord-328947-3l9ydspz author: Webb, L. G. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-328947-3l9ydspz.txt cache: ./cache/cord-328947-3l9ydspz.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-328947-3l9ydspz.txt' === file2bib.sh === id: cord-342825-s8ddek2f author: Kim, Ye Ji title: Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators date: 2016-08-26 pages: extension: .txt txt: ./txt/cord-342825-s8ddek2f.txt cache: ./cache/cord-342825-s8ddek2f.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-342825-s8ddek2f.txt' === file2bib.sh === id: cord-001859-d62iuk72 author: Baquero-Pérez, Belinda title: Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date: 2015-11-20 pages: extension: .txt txt: ./txt/cord-001859-d62iuk72.txt cache: ./cache/cord-001859-d62iuk72.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-001859-d62iuk72.txt' === file2bib.sh === id: cord-338053-8zlxsf1z author: Foo, Suan-Sin title: Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation date: 2015-02-19 pages: extension: .txt txt: ./txt/cord-338053-8zlxsf1z.txt cache: ./cache/cord-338053-8zlxsf1z.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-338053-8zlxsf1z.txt' === file2bib.sh === id: cord-348799-qu4zin3o author: Wu, Nannan title: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation date: 2019-10-10 pages: extension: .txt txt: ./txt/cord-348799-qu4zin3o.txt cache: ./cache/cord-348799-qu4zin3o.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-348799-qu4zin3o.txt' === file2bib.sh === id: cord-324928-cpryxa6p author: Lello, Laura Sandra title: Cross-utilisation of template RNAs by alphavirus replicases date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-324928-cpryxa6p.txt cache: ./cache/cord-324928-cpryxa6p.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-324928-cpryxa6p.txt' === file2bib.sh === id: cord-325825-0lyt8gfq author: Griffiths, Samantha J. title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 pages: extension: .txt txt: ./txt/cord-325825-0lyt8gfq.txt cache: ./cache/cord-325825-0lyt8gfq.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-325825-0lyt8gfq.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-351548-jvl63652 author: Juranic Lisnic, Vanda title: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date: 2013-09-26 pages: extension: .txt txt: ./txt/cord-351548-jvl63652.txt cache: ./cache/cord-351548-jvl63652.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-351548-jvl63652.txt' === file2bib.sh === id: cord-333473-c1lykari author: Irigoyen, Nerea title: High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling date: 2016-02-26 pages: extension: .txt txt: ./txt/cord-333473-c1lykari.txt cache: ./cache/cord-333473-c1lykari.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-333473-c1lykari.txt' Que is empty; done journal-plosPathog-cord === reduce.pl bib === id = cord-000007-h8upyzb1 author = Butler, Noah S. title = Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant date = 2008-10-24 pages = extension = .txt mime = text/plain words = 7690 sentences = 354 flesch = 47 summary = Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Enhancement strategies, which result in augmented responses to the native, subdominant epitope, have been described for both MHC class I and class II-restricted determinants, whereby the most common approaches involve generating a series of conserved and non-conserved mutations at MHC anchor residues, followed by an empiric determination of whether each individual substitution augments T cell effector function [12] . Immunization with the modified peptide resulted in an improved response to the native S598 epitope, demonstrating a true heteroclitic effect and suggesting that this strategy may have clinical applications for reducing viral titer and preventing CTL escape during chronic infections. Seven days following virus infection, brains were harvested from mice and the frequencies of epitope-specific CD8 T cells were determined by ex vivo stimulation and intracellular cytokine staining as described above. cache = ./cache/cord-000007-h8upyzb1.txt txt = ./txt/cord-000007-h8upyzb1.txt === reduce.pl bib === id = cord-000005-zt6i3o86 author = Bischof, Larry J. title = Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo date = 2008-10-10 pages = extension = .txt mime = text/plain words = 7600 sentences = 401 flesch = 56 summary = elegans and mammalian cells to PFTs. We demonstrate for the first time that the ire-1 -xbp-1 arm of the UPR (and to a lesser extent the atf-6 arm) is functionally important for defense against a pathogenic attack since loss of this pathway leads to animals hypersensitive to PFT, but not to other toxic insults. As shown, a strong and specific increase in GFP expression in the intestine can be seen in the presence of the PFT ( Figure 1B , middle panel), consistent with activation of the ire-1-xbp-1 pathway by Cry5B. Consistent with activation of the ire-1-xbp-1 pathway by p38 MAPK in response to PFT but not unfolded proteins, the full induction of both mRNAs by Cry5B, but not tunicamycin, is dependent on sek-1 MAPKK. Specifically, we find that bacterial pore-forming toxins (PFTs) activate the ire-1-xbp-1 branch of the ER Unfolded Protein Response (UPR) in C. cache = ./cache/cord-000005-zt6i3o86.txt txt = ./txt/cord-000005-zt6i3o86.txt === reduce.pl bib === id = cord-000127-tkxpjlyn author = Dermody, Terence S. title = Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity date = 2009-11-26 pages = extension = .txt mime = text/plain words = 2332 sentences = 115 flesch = 36 summary = The immunoglobulin superfamily (IgSF) of molecules contains several members that are expressed at the cell surface, bind diverse ligands, and contribute to a variety of cellular activities, including adhesion and immune responses. While structural information about com-plex formation is lacking for the IgSF receptors carcinoembryonic antigen-related cell adhesion molecule, nectin-1, nectin-2, and signaling lymphocyte-activation molecule (SLAM), biochemical studies also implicate their respective D1 domains in virus binding [11] [12] [13] [14] . The evolution of JAM family members prior to the biochemical means to efficiently and extensively diversify antigen receptor genes, along with the structural similarities in the binding surfaces of virus receptors and immunoglobulins, provides strong support for the contention that viruses and perhaps other pathogens that engage IgSF receptors contributed to the selection of humoral mediators of adaptive immunity. cache = ./cache/cord-000127-tkxpjlyn.txt txt = ./txt/cord-000127-tkxpjlyn.txt === reduce.pl bib === id = cord-262248-q5eijunp author = Casadevall, Arturo title = The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases date = 2015-04-23 pages = extension = .txt mime = text/plain words = 2631 sentences = 118 flesch = 37 summary = Currently, there are no drugs to treat Ebola, but, in the urgency and emergency triggered by the epidemic, two types of Ab-based therapies have been used: convalescent sera from patients who have recovered and a mAb cocktail known as ZMapp produced in plants [3] . For example, given that there is increasing evidence that antibiotic-induced disruptions of the microbiota are associated with deleterious effects in the treatment of bacterial diseases, the high specificity of Ab-based therapies offers a tremendous advantage. Regarding the limitation that highly specific Abs can fail to bind highly related variants, particularly for viruses, there are two strategies to overcome this problem: the development of Abs that target broadly neutralizing epitopes, as has now been demonstrated for HIV [8] , dengue [9] , and influenza viruses [10] , and the generation of Ab cocktails composed of Abs against multiple serotypes or variants, as has been done for rabies virus [11] and Clostridium difficile toxin [12] . cache = ./cache/cord-262248-q5eijunp.txt txt = ./txt/cord-262248-q5eijunp.txt === reduce.pl bib === id = cord-000025-6zrv687k author = Chachu, Karen A. title = Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection date = 2008-12-12 pages = extension = .txt mime = text/plain words = 6996 sentences = 340 flesch = 48 summary = In the absence of a cell culture system for HuNV, virus like particles (VLPs) that assemble when the viral capsid protein is expressed have been important for evaluating norovirus immune responses [20] [21] [22] [23] . To determine the role of T cells in clearance of acute MNV infection we inoculated WT, MHC Class II-/-, and MHC Class I6b2M-/-mice orally with MNV1.CW3 and measured viral titers in the distal ileum and MLN three, five, seven and 21 days post-infection ( Figure 4B-4E) . Together, these data from primary challenges of non-immune mice lacking antigen presenting molecules or depleted of specific T cell subsets demonstrated that CD4 T cells are important for efficient MNV clearance in the distal ileum especially at days three Lack of any of the three components of the adaptive response: B cells, CD4 T cells, or CD8 T cells significantly diminished vaccine effects generated by either live virus or VP1 capsid protein immunization, and delayed viral clearance during primary infection. cache = ./cache/cord-000025-6zrv687k.txt txt = ./txt/cord-000025-6zrv687k.txt === reduce.pl bib === id = cord-000018-amvlm09p author = Pauli, Eva-K. title = Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression date = 2008-11-07 pages = extension = .txt mime = text/plain words = 9011 sentences = 515 flesch = 53 summary = Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. These results are consistent with data gained from previous experiments in Vero cells ( Figure 1E ) and indicate that neither induction of SOCS-3 mRNA nor inhibition of STAT phosphorylation is dependent on virus-induced type I IFN expression. To answer the question whether enhanced STAT phosphorylation in SOCS-3 deficient cells would also lead to enhanced expression of ISGs, total RNA was isolated at different time points p.i. from infected wild type and knock out cells and monitored for induction of SP110, IRF-1 and OAS1 ( Figure 7E, 7F and 7G ). cache = ./cache/cord-000018-amvlm09p.txt txt = ./txt/cord-000018-amvlm09p.txt === reduce.pl bib === id = cord-002893-d7hetoq0 author = Meng, Xiangzhi title = A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection date = 2018-02-15 pages = extension = .txt mime = text/plain words = 6300 sentences = 322 flesch = 52 summary = Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. Both paralogs are antagonized by VACV K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is resistant to the C7 homolog encoded by a group of poxviruses with a narrow host range in ruminants, indicating that host species-specific difference in SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission. VACV K1, C7 and C7 homologs from diverse poxviruses could overcome hSAMD9L restriction, but the sheeppox virus C7 homolog has reduced potency due to the variation of two residues To find out whether mammalian poxviruses could overcome the restriction of hSAMD9L, we induced hSAMD9L expression in ΔhSAMD9 HeLa cells with 200 U/ml of IFN-β and then infected the cells with our panel of vK1L -C7L --derived VACVs. Viruses that expressed VACV-K1, VACV-C7, MYXV-M62, SPPV-063, SWPV-064 and YLDV-67 (but not MYXV-M63 and MYXV-M64) grew in IFN-treated ΔhSAMD9 cells (Fig 5A) , indicating that all known SAMD9 antagonists could also antagonize hSAMD9L. cache = ./cache/cord-002893-d7hetoq0.txt txt = ./txt/cord-002893-d7hetoq0.txt === reduce.pl bib === id = cord-000164-094d0rn6 author = Suthar, Mehul S. title = IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity date = 2010-02-05 pages = extension = .txt mime = text/plain words = 8172 sentences = 340 flesch = 44 summary = Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. To define the role of IPS-1 in controlling virus replication and innate immunity in myeloid cells, we analyzed WNV infection and host responses in primary bone marrow-derived DC and Mw recovered from wild type and IPS-1 2/2 mice. cache = ./cache/cord-000164-094d0rn6.txt txt = ./txt/cord-000164-094d0rn6.txt === reduce.pl bib === id = cord-000318-wk2u2a9w author = Lamb, Daniel title = Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins date = 2011-02-03 pages = extension = .txt mime = text/plain words = 7494 sentences = 317 flesch = 47 summary = Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry. The BLV crystal structure and our analysis of HTLV-1 and BLV envelope-mediated membrane fusion reveal an important role for electrostatic interactions in binding of the LHR to the grooves of the coiled coil. cache = ./cache/cord-000318-wk2u2a9w.txt txt = ./txt/cord-000318-wk2u2a9w.txt === reduce.pl bib === id = cord-000232-boto4h8x author = Danthi, Pranav title = Bid Regulates the Pathogenesis of Neurotropic Reovirus date = 2010-07-01 pages = extension = .txt mime = text/plain words = 9287 sentences = 439 flesch = 37 summary = Blockade of NF-kB signaling, which diminishes apoptosis induction by reovirus [8, 28] , prevents cleavage of Bid. In comparison to wild-type mice, Bid-deficient mice display diminished susceptibility to reovirus-induced CNS disease following either peroral (PO) or intracranial (IC) inoculation. To directly test whether Bid is required for apoptosis induction following reovirus infection, we compared reovirus-induced apoptosis in wild-type and Bid-deficient MEFs. For these experiments, MEFs were infected with T3D, and apoptosis was assessed by chemiluminescent measurement of the activity of caspase-3 and caspase-7, which serve as effector caspases for both the extrinsic and intrinsic apoptotic pathways ( Figure 2A ). Increase in caspase-3/7 activity following treatment of each cell type with a broad-spectrum protein kinase inhibitor, staurosporine, was equivalent (,5-fold), demonstrating that although Bid-deficient cells possess functional death-signaling pathways, they resist apoptosis induction by reovirus. Analogous to treatment with TNFa, a control NF-kB agonist, reovirus infection resulted in equivalent (,2-to 3-fold) activation of NF-kB-driven gene expression in wild-type and Bid-deficient cells ( Figure 3A ). cache = ./cache/cord-000232-boto4h8x.txt txt = ./txt/cord-000232-boto4h8x.txt === reduce.pl bib === id = cord-280621-tph5n7ak author = Kim, Yunjeong title = Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor date = 2016-03-30 pages = extension = .txt mime = text/plain words = 7417 sentences = 354 flesch = 52 summary = Shifts in tissue or cell tropism and resulting changes in virulence have also been reported for coronaviruses; porcine respiratory coronavirus causes mild respiratory infection in pigs and presumably arose from transmissible gastroenteritis virus (TGEV), the etiologic agent of gastroenteritis in young pigs with a high fatality, by spontaneous mutations and/or deletions in its genome [9] . Effective treatment intervention for coronavirus infections with an immunopathological component, such as SARS, MERS and FIP, is speculated to involve the judicious use of immunomodulatory agents to enhance protective host immunity and decrease pathological immune responses and antiviral drugs to directly inhibit viral replication. These results on viral titers show that FIPV 3CLpro is a valid target for FIPV antiviral drugs and GC376 can effectively reduce the virus load in the macrophages from the ascites and the omentum of cats with FIP. cache = ./cache/cord-280621-tph5n7ak.txt txt = ./txt/cord-280621-tph5n7ak.txt === reduce.pl bib === id = cord-003982-7v5xl1s3 author = Trus, Ivan title = Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring date = 2019-11-14 pages = extension = .txt mime = text/plain words = 10473 sentences = 554 flesch = 49 summary = title: Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome. In our porcine model studies, subclinical persistent in utero infection in mid-gestation also increased interferon alpha (IFN-α) levels in fetal blood plasma and amniotic fluid, while IFN-α was below the detection limit in all control fetuses [18] . We performed a mixing test (S2 Video) on control and affected piglets at 35 days of age to identify whether subclinical in utero ZIKV infection and social stress have synergistic effects on cytokine responses in offspring. cache = ./cache/cord-003982-7v5xl1s3.txt txt = ./txt/cord-003982-7v5xl1s3.txt === reduce.pl bib === id = cord-004428-ob5igsv5 author = Kizziah, James L. title = Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage date = 2020-02-18 pages = extension = .txt mime = text/plain words = 8039 sentences = 366 flesch = 56 summary = Crystal structures have also been determined for Bacillus phage SPP1 Dit [25] and the baseplates of lactococcal phages p2 and TP901-1, which include Dit, Tal, BppU, and receptor binding proteins that are not similar to the ϕ11 RBP [23, 26] . Atomic models for MTP (gp53), Dit (gp58), RBP (gp61), and parts of Tal (gp59), FibL (gp62), FibU (gp68) and TMP (gp57) were built into either the C6 or C3 baseplate reconstructions, using I-TASSER models as starting points [29] , complemented with real-space refinement in PHENIX [30] . RBP is a trimeric protein consisting of four domains: an N-terminal α-helical coiled-coil "stem" domain (residues 1-142) that is folded by 155˚at a central hinge; a fivebladed β-propeller "platform" domain (residues 143-442) that was previously suggested to bind to the GlcNAc residues of WTA on the host cell surface [21, 24] ; and two highly similar C-terminal "tower" domains (residues 443-636; S1 Table) , each consisting of a bent β-sheet superposed by an α-helix (Fig 5A) . cache = ./cache/cord-004428-ob5igsv5.txt txt = ./txt/cord-004428-ob5igsv5.txt === reduce.pl bib === id = cord-001109-xs7df6a7 author = Tapia, Karla title = Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity date = 2013-10-31 pages = extension = .txt mime = text/plain words = 7169 sentences = 360 flesch = 50 summary = We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. To further investigate the cellular mechanisms responsible for the efficient activation of the antiviral response by SeV DVGs, we evaluated the phosphorylation of transcription factors that are critical for the expression of type I IFNs in cells infected with equivalent amounts of infectious particles of a SeV strain Cantell stock containing high levels of copy-back DVGs (SeV Cantell HD) or with SeV Cantell depleted of DVGs (SeV Cantell LD). Based on the potent ability of SeV stocks containing a high content of copy-back DVGs to induce the host response to infection in vitro [23, 24, 25, 28] (Fig. 1 ) and on our prior reports of strong host responses to DVGs regardless of the presence of functional virus-encoded antagonists [23, 24] , we hypothesized that DVGs that arise in situ during viral infections provide essential stimuli to initiate an antiviral immune response. cache = ./cache/cord-001109-xs7df6a7.txt txt = ./txt/cord-001109-xs7df6a7.txt === reduce.pl bib === id = cord-000409-lpf9lpky author = Chen, Yongwen title = Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date = 2011-07-07 pages = extension = .txt mime = text/plain words = 5540 sentences = 296 flesch = 49 summary = Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. In all, these results demonstrated that PD-1 deficiency led to enhanced pathological damage by MHV-3 in the liver, spleen, lymph node and thymus, where higher levels of PD-1-positive cells were found after infection. Results showed that the expression of FGL2 was principally associated with CD31-positive endothelial cells, CD68-positive macrophages and CD11c-positive DCs. Surprisingly, significantly higher levels of FGL2 were observed after infection in all of PD-1-deficient organs, including the liver, thymus, spleen, lymph nodes, and serum than that in those from WT littermates. However, the number of Foxp3-positive cells in the liver, spleen, lymph node or thymus was not significantly different between PD-1-deficient mice and their WT littermates after 72 h of MHV-3 infection (Fig. S3) . cache = ./cache/cord-000409-lpf9lpky.txt txt = ./txt/cord-000409-lpf9lpky.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-000933-nn9gj0z1 author = Krzyzaniak, Magdalena Anna title = Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein date = 2013-04-11 pages = extension = .txt mime = text/plain words = 10347 sentences = 569 flesch = 54 summary = To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. To determine the pathway of RSV entry into HeLa and A549 cells, we developed quantitative fluorescence-activated cell sorting (FACS) assays and complemented them with confocal microscopy to monitor cell binding of RSV, endocytosis, fusion, and infection. Since we did not detect free capsids that would stain only for N or P (data not shown), we used the presence of the capsid antigens to distinguish between intact RSVs and VLPs. When purified virus preparations were incubated with HeLa cells at 4uC, immunoblotting after SDS-PAGE showed that more than half of the input N and P associated with the cells indicating that RSV binding in the cold was efficient (Fig. 1C) . cache = ./cache/cord-000933-nn9gj0z1.txt txt = ./txt/cord-000933-nn9gj0z1.txt === reduce.pl bib === id = cord-290617-45be6gxe author = Poulain, Florian title = Footprint of the host restriction factors APOBEC3 on the genome of human viruses date = 2020-08-14 pages = extension = .txt mime = text/plain words = 10515 sentences = 610 flesch = 56 summary = Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. By breaking down the human viruses into their respective Baltimore's group (S3 Fig), we observed that NTC depletion is not present in reverse transcribing nor in negative sense single strand RNA viruses. We also observed a mild general NCC depletion in single strand DNA and double strand RNA viruses, justifying further investigation for a possible A3G-induced footprint (S1 Fig). In order to identify A3-footprinted viruses, we detailed the NTC and NNGANN ratios for 870 human viral species (Fig 4A) . B. The observed/expected ratios of TC dinucleotide at various codon positions and on both strands (i.e. NNTCNN, TCN, NTC, GAN, NGA and NNGANN) were calculated for the putative A3-footprinted viral species and depicted by a heatmap. cache = ./cache/cord-290617-45be6gxe.txt txt = ./txt/cord-290617-45be6gxe.txt === reduce.pl bib === id = cord-001257-t21l6i3f author = Kovalev, Nikolay title = The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication date = 2014-04-17 pages = extension = .txt mime = text/plain words = 10621 sentences = 624 flesch = 58 summary = Novel pro-viral function of AtRH2, AtRH5 and the yeast Dbp3p and Fal1p is to bind to the viral replication enhancer present in the tombusvirus minus-strand RNA To test if AtRH2, AtRH5 and the yeast Dbp3p and Fal1p play a comparable role with the previously analyzed yeast Ded1p (human DDX3-like) and Dbp2p (human p68-like) and the ortologous AtRH20 DEAD-box helicases [30, 49] , first we performed in vitro RNA binding experiments with affinity-purified recombinant helicase proteins. The replication process leads to the production of abundant (+)RNA progeny, while the (2)RNA templates are likely sequestered in dsRNA forms within the VRCs. The presented in vitro data based on the solubilized/purified tombusvirus replicase and the CFE assay containing the membrane-bound VRC indicate that the eIF4AIIIlike RNA helicases can mainly stimulate TBSV (+)-strand synthesis, while their effects on (2)RNA synthesis have not been observed (not shown). cache = ./cache/cord-001257-t21l6i3f.txt txt = ./txt/cord-001257-t21l6i3f.txt === reduce.pl bib === id = cord-001636-khrx6rnh author = Bordería, Antonio V. title = Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype date = 2015-05-05 pages = extension = .txt mime = text/plain words = 7524 sentences = 358 flesch = 50 summary = The total number of minority variants within the P1 structural coding region also significantly increased over the passage series (Fig 1G) , yet there were no significant differences between the numbers observed in Hela and A549 cell passage. The mutations that arise from adaptive passage map to receptor binding sites in a cell-type specific manner Although the HeLa and A549 cell passage series presented similar mean genetic diversity at passage 40 (Fig 1E-1G , P = 0.314), we mined the deep sequence data for all minority variants above 1% frequency that might explain adaptation in each condition (Table 1 ). Given the different frequencies of minority variants observed at passage 40, we examined the patterns of emergence and sequential adaptation to novel environments by deep sequencing every second passage in the A549 cell series (Fig 3 and S1 Dataset). cache = ./cache/cord-001636-khrx6rnh.txt txt = ./txt/cord-001636-khrx6rnh.txt === reduce.pl bib === id = cord-000729-iq30z094 author = Marsh, Glenn A. title = Cedar Virus: A Novel Henipavirus Isolated from Australian Bats date = 2012-08-02 pages = extension = .txt mime = text/plain words = 6101 sentences = 277 flesch = 49 summary = The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrinB2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. As part of our on-going field studies on HeV genetic diversity and infection dynamics in the Queensland flying fox populations, urine samples were collected on a regular basis for PCR and virus isolation. CedPV is more closely related to HeV and NiV than henipavirus-like sequences detected in African bats [26, 32] as shown in a phylogenetic tree based on the only sequences available of a 550-nt L gene fragment (Fig. S5) . cache = ./cache/cord-000729-iq30z094.txt txt = ./txt/cord-000729-iq30z094.txt === reduce.pl bib === id = cord-266078-h53zpjab author = McGuckin Wuertz, Kathryn title = STING is required for host defense against neuropathological West Nile virus infection date = 2019-08-15 pages = extension = .txt mime = text/plain words = 9796 sentences = 470 flesch = 49 summary = Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. In vivo, STING-/mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. In the CNS however, we observed a trend toward increased viral RNA and innate immune gene expression at 8 dpi in WNV-infected STING-/-mice, similar to that observed in BMDM (Fig 3A and 3D) . These observations suggest that STING plays a role in directing or maintaining the T cell response to specific loci within the CNS or that initial viral infection led to increased STING is required for host defense against neuropathological West Nile virus infection recruitment of a localized adaptive immune response that resulted in immunopathology. cache = ./cache/cord-266078-h53zpjab.txt txt = ./txt/cord-266078-h53zpjab.txt === reduce.pl bib === id = cord-001859-d62iuk72 author = Baquero-Pérez, Belinda title = Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date = 2015-11-20 pages = extension = .txt mime = text/plain words = 15958 sentences = 876 flesch = 50 summary = Similar Hsc70 localization was seen during early lytic replication (12 h reactivation), when RTA protein was diffuse in the nucleus, Successful enrichment of the nuclear envelope region and associated KSHV RTCs in HEK-293T rKSHV.219 cells. These results clearly demonstrate that KSHV specifically redistributes the molecular chaperones, Hsc70 and iHsp70, from the cytoplasm to the nucleus, in contrast to Grp78, which coincides with the initial formation of KSHV RTCs. Treatment with the small molecule inhibitor VER-155008 abrogated viral protein synthesis at non-cytotoxic concentrations Members of the HSP70 chaperone family possess an N-terminal nucleotide binding domain with ATPase activity which is essential for their function. Therefore to ascertain whether Hsp70 isoforms could stabilise the essential KSHV lytic proteins RTA and ORF57, TREx BCBL1-RTA cells were reactivated for 24 h to allow sufficient viral protein expression followed by addition of DMSO control or VER-155008 in conjunction with cycloheximide (CHX) at 50 μg/ml to block de novo protein synthesis. cache = ./cache/cord-001859-d62iuk72.txt txt = ./txt/cord-001859-d62iuk72.txt === reduce.pl bib === id = cord-003441-810r5q03 author = Dzimianski, John V. title = Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity date = 2019-01-10 pages = extension = .txt mime = text/plain words = 10973 sentences = 578 flesch = 54 summary = Specifically, that CCHFV vOTU DUB activity is not as promiscuous towards ubiquitinated host proteins as it first seemed based on the overexpression studies, but appears to be restricted to a targeted subset of cellular substrates associated with suppression of RIG-I-mediated early cellular responses to infection. Additionally, a structure of the FARV vOTU provides details into the structural nature of the additional residues in Hughes orthonairovirus vOTUs. Structureinformed mutagenesis of FARV vOTU identified residues involved specifically in di-Ub binding, representing the first report of the role of a second site involved in di-Ub binding in nairovirus vOTUs. This novel enzymatic and structural data not only provides insight into the nature of vOTU diversity, but also lays a foundation for understanding the impact of the vOTU interaction with the innate immune response and its connection to viral pathogenesis. Intriguingly, the vOTUs showed a diverse range of activity towards Ub. In general, vOTUs can be divided into groups possessing high (CCHFV, HAZV, NSDV/GANV, TAGV), moderate (DUGV, KUPEV, FARV, QYBV, ISKV), or low activity (ERVEV, DGKV, LPHV, HpTV-1) (Fig 2A) . cache = ./cache/cord-003441-810r5q03.txt txt = ./txt/cord-003441-810r5q03.txt === reduce.pl bib === id = cord-001541-5d64esp4 author = Walker, Peter J. title = Evolution of Genome Size and Complexity in the Rhabdoviridae date = 2015-02-13 pages = extension = .txt mime = text/plain words = 9157 sentences = 398 flesch = 45 summary = We demonstrate that remarkable changes in genome size and complexity have occurred in rhabdoviruses in a clade-specific manner, primarily by extension and insertion of additional transcriptional units in the structural protein gene junctions, followed by occasional losses. All rhabdovirus genomes contained the five canonical structural protein genes (N, P, M, G and L); however, there was remarkable diversity in the number and location of other long ORFs. Across the data set, we identified 179 additional ORFs 180 nt in length of which 142 shared no detectable protein sequence similarity with any other protein in our data set or with those in public databases (S2 Table) . Interestingly, although substantial variation in the length of gene junctions was observed in several genera (including ephemeroviruses and lyssaviruses), most variation in genome size occurred as the result of the presence of new, non-canonical ORFs in the regions between the structural protein genes (Table 1) . cache = ./cache/cord-001541-5d64esp4.txt txt = ./txt/cord-001541-5d64esp4.txt === reduce.pl bib === id = cord-312743-9e4yufo5 author = Breiman, Adrien title = Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2 date = 2020-05-21 pages = extension = .txt mime = text/plain words = 1388 sentences = 66 flesch = 45 summary = These observations suggested that, when produced in cells that express the A or B blood group enzymes, infectious SARS virions are decorated by the corresponding glycan antigens and that the presence of anti-A and anti-B antibodies in blood group O individuals could prevent infection by blocking virus attachment and entry. We therefore hypothesize that as they are produced in cells coexpressing the ACE2 receptor and either the αGal, NeuGc, or A/B blood group antigens, both SARS-CoV and SARS-CoV2 harbor the corresponding glycan epitopes. Likewise, impairment of transmission by the anti-blood group antibodies may not work to its full potential because of their variable titers in the population and of the high affinity of the SARS-CoV2 for ACE2 [18] , rendering its neutralization more difficult. cache = ./cache/cord-312743-9e4yufo5.txt txt = ./txt/cord-312743-9e4yufo5.txt === reduce.pl bib === id = cord-269466-9hnal9ad author = Agbeci, Maxime title = Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus date = 2013-10-03 pages = extension = .txt mime = text/plain words = 7184 sentences = 391 flesch = 49 summary = In this study, we used a novel dual gene cassette construct that differentiated primary infected cells from cells infected after virus intercellular movement to show that the early as well as the late secretory pathway, but not endocytosis, was important for TuMV transport. By using a dual cassette of genes encoding fluorescent proteins that can differentiate between primary infected cells and cells infected after intercellular transport, we provide evidence that turnip mosaic virus (TuMV) needs a functional secretory pathway where pre-and post-Golgi trafficking and the actomyosin network are important for its movement. Fig. 2E shows that that there was no significant difference in the ratio of red over green fluorescence during BFA and CMA treatments compared with the no inhibitor treatment (TuMV alone) at 4 dpinf, indicating that viral protein production in the primary infected cells was not affected by the drug treatments. cache = ./cache/cord-269466-9hnal9ad.txt txt = ./txt/cord-269466-9hnal9ad.txt === reduce.pl bib === id = cord-001700-c6elsnag author = Fusco, Marnie L. title = Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs date = 2015-06-26 pages = extension = .txt mime = text/plain words = 6459 sentences = 329 flesch = 57 summary = Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. To generate MARV GP-specific mAbs, BALB/c mice were immunized with GPΔmuc antigens from either MARV strain Ci67, Musoke, Angola, or Ravn ( Fig 1A) . To characterize the binding of mAbs, we performed enzyme-linked immunosorbent assays (ELISAs) with recombinant GPs from four MARV strains, and determined EC50 values for binding with different forms of MARV Ravn GP: GP, GPΔmuc, GPcl (Fig 2A) . Two of the highly cross-reactive MARV antibodies, mAbs 40G1 and 2D8, also exhibit binding to Ebola, Sudan, Bundibugyo and Reston virus mucin-deleted GPs by ELISA (Fig 5A) . cache = ./cache/cord-001700-c6elsnag.txt txt = ./txt/cord-001700-c6elsnag.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-304815-3datxv8j author = Gronvall, Gigi Kwik title = The Scientific Response to a Pandemic date = 2006-02-24 pages = extension = .txt mime = text/plain words = 1522 sentences = 92 flesch = 49 summary = More than 150 scientists and public health practitioners from 25 countries gathered in Lyon, France, to hear speakers from the WHO, the European Commission, scientific journals, Interpol, and public health networks-many of the institutions and individuals who will likely play key roles in the global response to the next pandemic. By discussing the biosafety and biosecurity challenges presented by past epidemics such as SARS, participants recognized the importance of scientific and public health collaboration in combating disease-and the need to plan. Researchers will need to share biological samples between laboratories, sometimes internationally; decision makers and journalists will want the latest information, which may not be peer reviewed; and researchers will risk contracting the disease they research, which could then spread outside of the laboratory. Scientists need access to samples from patients and laboratories in order to conduct research and public health surveillance, as well as to develop diagnostic tests. cache = ./cache/cord-304815-3datxv8j.txt txt = ./txt/cord-304815-3datxv8j.txt === reduce.pl bib === id = cord-002423-1u44tdrj author = Geoghegan, Jemma L. title = Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families date = 2017-02-08 pages = extension = .txt mime = text/plain words = 6186 sentences = 267 flesch = 44 summary = While this method does not explicitly model host-switching events, it does provide a simple means to compare multiple topologies of virus-host pairs, and accounts for differences in sample size and the fact that several viruses from a specific family can infect a single host species. Across the data set as a whole we found that all virus families displayed relatively large tree topological distances with nPH85 values of !0.6, suggesting that cross-species transmission is widespread, at least at the family-level (Fig 2; S3 Table) . As with the analysis of topological distances, this revealed that cross-species transmission was the most common evolutionary event in all virus families studied here, with co-divergence consistently less frequent (with the possible exception of the Hepadnaviridae-see below), and lineage duplication and extinction playing a much more minor role. To investigate the comparative prevalence of cross-species transmission among viruses we measured the congruence between virus and host phylogenetic trees using a normalized tree topological distance-based approach (nPH85, [14] ). cache = ./cache/cord-002423-1u44tdrj.txt txt = ./txt/cord-002423-1u44tdrj.txt === reduce.pl bib === === reduce.pl bib === id = cord-278511-je1509ar author = Wang, David title = 5 challenges in understanding the role of the virome in health and disease date = 2020-03-26 pages = extension = .txt mime = text/plain words = 2166 sentences = 107 flesch = 38 summary = An even more significant problem is that in most virome studies, more than 50% of the sequences in virus-enriched preparations have no detectable sequence similarity to any known reference sequences; these unalignable sequences are referred to as viral "dark matter" [8] and may include novel, highly divergent viruses that are unrecognizable. To illustrate this point, the United States National Institutes of Health (NIH) virology study sections address only "non-bacteriophage viral genetics, infection and replication, cellular and host responses to viral infections, and mechanisms of viral disease pathogenesis." Thus, there is a great need to bring these disparate communities together in order to collectively attack questions associated with the virome, especially as more complex trans-kingdom interactions are identified linking phages, bacteria, eukaryotic viruses, and eukaryotic cells. With new cell-culture systems and animal models for novel viruses, there will ideally be studies that attribute causal roles for some of the associations. cache = ./cache/cord-278511-je1509ar.txt txt = ./txt/cord-278511-je1509ar.txt === reduce.pl bib === === reduce.pl bib === id = cord-287219-qxkwjkif author = Geisbert, Thomas W. title = Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates date = 2008-11-28 pages = extension = .txt mime = text/plain words = 5413 sentences = 247 flesch = 44 summary = In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). Therefore, we conducted a study to assess the pathogenicity and protective efficacy of the recombinant VSVbased ZEBOV vaccine vector in rhesus macaques that were infected with simian-human immunodeficiency virus (SHIV) which is known to deplete the populations of naive CD4+ T cells, naive CD8+ T cells, and memory CD4+ T cells in these animals [22, 23] . Disease progressed in two of the VSVDG/ZEBOVGP-vaccinated SHIV-infected monkeys (Subject #5 and 6) and both of the placebo control animals with the development of additional evidence of clinical illness including increased levels of serum enzymes associated with liver function, depression, anorexia, and the appearance of macular rashes (Table 3 ). cache = ./cache/cord-287219-qxkwjkif.txt txt = ./txt/cord-287219-qxkwjkif.txt === reduce.pl bib === id = cord-297702-vxcj25sn author = Chen, Yuxin title = A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients date = 2020-09-10 pages = extension = .txt mime = text/plain words = 5253 sentences = 250 flesch = 46 summary = We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. In this retrospective study, we successively monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the NP protein, RBD protein, S1 protein, and ECD protein in 19 non-severe and 7 severe COVID-19 patients during the disease progression. The severe patients and non-severe patients had comparable reduced fold of IgM, IgG, and IgA binding titer specific to RBD, ECD, S1, and NP protein and neutralization activities. Furthermore, 80.7% of the convalescent sea from COVID-19 patients displayed varying levels of neutralization activities against SARS-CoV-2, which correlated with S1-specific and ECD-specific IgA responses in non-severe patients. cache = ./cache/cord-297702-vxcj25sn.txt txt = ./txt/cord-297702-vxcj25sn.txt === reduce.pl bib === === reduce.pl bib === id = cord-253783-3a1qde41 author = Johnson, Christopher J title = Prions Adhere to Soil Minerals and Remain Infectious date = 2006-04-14 pages = extension = .txt mime = text/plain words = 5461 sentences = 283 flesch = 51 summary = We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. X-ray diffraction analysis provided no evidence that PrP Sc entered Mte interlayer spaces (Mte d 001 spacings were 1.22 nm and 1.47 nm before and after PrP Sc adsorption, respectively); prion protein appeared to adsorb to only external clay surfaces. Prion protein desorbed from Kte and quartz did not exhibit a change in molecular mass ( Figure 1A ), suggesting that surface properties specific to Mte were responsible for the cleavage. To control for any unbound prion protein that may have cosedimented with Mte particles, mineral-free PrP Sc suspensions were processed in the same manner as in sorption experiments. Our results demonstrate that all soil mineral surfaces examined bound PrP Sc and that Mte and quartz have larger specific binding capacities for PrP Sc than does Kte (Figure 1 ). cache = ./cache/cord-253783-3a1qde41.txt txt = ./txt/cord-253783-3a1qde41.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-265947-7j9qqi8w author = Du, Wenjuan title = The 2(nd) sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance date = 2019-06-10 pages = extension = .txt mime = text/plain words = 9564 sentences = 464 flesch = 50 summary = NAs of avian, but not human viruses, contain a functional 2(nd) sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. Using a recently established BLI-based kinetic binding assay [37] an enhanced initial binding rate to 3'SLNLN but not 6'SLNLN ( Fig 4A and 4B ), was observed for hH3aN2 virus containing Role for 2 nd SIA-binding site of IAV NA in HA-NA-receptor balance a functional 2SBS in comparison to hH3hN2. We therefore studied the effect of the 2SBS in NA when combined with an avian-type Role for 2 nd SIA-binding site of IAV NA in HA-NA-receptor balance HA preferring binding to α2,3-linked SIAs. We generated the corresponding recombinant A/ Hong Kong/1/68 (H3N2) viruses containing 7 amino acid substitutions in the HA (see S8A Fig) . cache = ./cache/cord-265947-7j9qqi8w.txt txt = ./txt/cord-265947-7j9qqi8w.txt === reduce.pl bib === id = cord-001992-m4k20i7g author = Ziegler, Christopher M. title = The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles date = 2016-03-24 pages = extension = .txt mime = text/plain words = 13157 sentences = 580 flesch = 53 summary = We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. Given the important role of the LCMV matrix protein and its late domain motif in regulating viral budding [10, 11] , we next investigated the specific effect these point mutations had on Z's budding efficiency in a VLP release assay. To investigate the protein and genome composition of virions containing mutated late domains, an equivalent quantity of cell-free infectious virus particles from each rLCMV strain was concentrated for screening. Limiting dilutions of this UV-treated sample were applied to Vero E6 cells, followed by the addition of a fixed quantity of LCMV PFUs. As shown in Fig 5A, this allows for the determination of LCMV DI particle activity and is expressed as plaque interfering units 50 (PIU 50 ) per mL of a given sample. cache = ./cache/cord-001992-m4k20i7g.txt txt = ./txt/cord-001992-m4k20i7g.txt === reduce.pl bib === id = cord-268388-kkhuzf3p author = Sharif-Yakan, Ahmad title = Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date = 2014-12-04 pages = extension = .txt mime = text/plain words = 2507 sentences = 141 flesch = 50 summary = Two years have passed since the initial description of the Middle East respiratory syndrome coronavirus (MERS-CoV), yet the epidemic is far from being controlled. First reported in 2012 [1] , Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus and the first lineage 2C Betacoronavirus known to infect humans [2] . Middle east respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, qatar Middle east respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: A descriptive study Clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: A report of nosocomial transmission Clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: An observational study cache = ./cache/cord-268388-kkhuzf3p.txt txt = ./txt/cord-268388-kkhuzf3p.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-314451-mqnqjn0c author = Roberts, Anjeanette title = A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date = 2007-01-12 pages = extension = .txt mime = text/plain words = 9794 sentences = 433 flesch = 48 summary = To generate a model that satisfies these criteria, we have serially passaged SARS-CoV in the respiratory tract of young BALB/c mice, resulting in a lethal virus that causes dosedependent weight loss and mortality associated with higher viral titers in the respiratory tract than are seen with the wildtype virus and with histopathologic findings of severe pulmonary disease. Northern blot analysis of RNA from infected Vero E6 cells indicated that genomic vRNA and viral mRNA and all eight sub-genomic mRNAs were present in similar ratios for the recombinant viruses and MA15 virus as for SARS-CoV (Urbani) ( Figure 2A ). In order to evaluate whether changes in tissue tropism or levels of viral replication could contribute to the lethal phenotype of the MA15 virus, viral titers in lungs, spleen, liver, and brain of BALB/c mice were determined at various time points following intranasal inoculation with SARS-CoV (Urbani) or MA15. cache = ./cache/cord-314451-mqnqjn0c.txt txt = ./txt/cord-314451-mqnqjn0c.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-002125-anp238gu author = Effantin, Grégory title = Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture date = 2016-07-11 pages = extension = .txt mime = text/plain words = 8022 sentences = 401 flesch = 55 summary = Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP). In order to obtain structural insight into PFV organization at medium resolution we used cryo-electron tomography (cryo-ET) and microscopy (cryo-EM) to analyze isolated wild-type particles and variants with mutations in PFV Gag and Env proteins. To gain more insights into the structure of the PFV glycoprotein, we use 3D reconstructions of iNAB and iFuse Env hexagonal assemblies of six trimers determined by subtomogram averaging as initial references for automatic particle selection of micrographs acquired by cryo-EM (S4 Fig) (see Material and Methods). cache = ./cache/cord-002125-anp238gu.txt txt = ./txt/cord-002125-anp238gu.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-260949-w2xuf15h author = Galluzzi, Lorenzo title = Viral Control of Mitochondrial Apoptosis date = 2008-05-30 pages = extension = .txt mime = text/plain words = 10923 sentences = 533 flesch = 37 summary = Bcl-2/Bcl-X L stabilizes mitochondrial membranes via multiple mechanisms, including (1) the sequestration into inactive complexes of its proapoptotic counterparts, Bax, Bak, and BH3only proteins (e.g., Bid) (for review: [S65,S78]), (2) inhibitory interactions with PTPC constituents, in particular with VDAC and the adenine nucleotide translocase (ANT) [12, 14] , (3) an enhancement of Cyt c oxidase activity and mitochondrial respiration [S79], and/or (4) indirect effects on intracellular Ca 2+ stores of the ER [S80,S81]. With regard to this, viral factors can be classified into one of the four following subgroups: proapoptotic proteins (1) that insert into mitochondrial membranes and hence trigger MMP through the action of amphipathic a-helical domains or (2) that promote MMP indirectly, through the activition of host-encoded factors (Table 1) , and antiapoptotic modulators (3) that exhibit sequence and/or structural similarity to multidomain BH1-4 members of the Bcl-2 family (so-called viral Bcl-2 proteins [vBcl-2s]) or (4) that inhibit apoptosis via other mechanisms (Table 2) . cache = ./cache/cord-260949-w2xuf15h.txt txt = ./txt/cord-260949-w2xuf15h.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-281404-5a8au32c author = Gastaldello, Stefano title = Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date = 2013-10-10 pages = extension = .txt mime = text/plain words = 7139 sentences = 337 flesch = 42 summary = The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Here we report that induction of the productive virus cycle has no appreciable effects on the global levels of protein ubiquitination but is accompanied by a BPLF1-dependent decrease of cullin neddylation and stabilization of nuclear CRL substrates. The Akata-Bx1 cell line was used to study the contribution of the Ub-and NEDD8-specific deconjugase activities of the EBV large tegument protein BPLF1 to the productive virus cycle. In order to assess whether this regulatory interaction may operate during virus replication, the productive cycle was induced in Akata-Bx1 cells transiently transfected with plasmids expressing Myc-tagged CAND1 or the CAND1 Nterminus that compete for BPLF1 binding to cullins, or, as controls, the CAND1 C-terminus that binds to the opposite end of the cullin scaffold, and the empty vector ( Figure 5A ). cache = ./cache/cord-281404-5a8au32c.txt txt = ./txt/cord-281404-5a8au32c.txt === reduce.pl bib === id = cord-002542-f7l4ty2j author = Jaworski, Elizabeth title = Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus date = 2017-05-05 pages = extension = .txt mime = text/plain words = 11789 sentences = 535 flesch = 49 summary = Using a combination of longand short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. By combining these data, we aimed to determine the correlation of recombination events within single RNA virus genomes, characterize the distribution of defective RNA genomes, and determine the exact make-up of DI-RNAs during serial passaging of FHV in cell culture. This observation indicates the protection of cells from infection and/or CPE when supplied with a large dose of viral particles that contain a large proportion of DI-RNAs. In this manuscript, we sought to provide a thorough and comprehensive analysis of the frequency and identity of recombination events present during the serial passaging of Flock House virus in cell culture in order to elucidate the pathways and mechanism of DI-RNA emergence and evolution. cache = ./cache/cord-002542-f7l4ty2j.txt txt = ./txt/cord-002542-f7l4ty2j.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-268677-ytxrrslz author = Züst, Roland title = Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques date = 2013-08-01 pages = extension = .txt mime = text/plain words = 7936 sentences = 436 flesch = 55 summary = Here we demonstrate that DENV strains bearing a mutation in the catalytic site of the 29-O-MTase replicated to high titres in cell culture whereas these mutant viruses were highly attenuated in mice and rhesus monkeys. Mice and monkeys infected with the mutant virus developed an immune response that fully protected them from a challenge with wild-type virus. These data suggest that vaccination with the E216A/E217A mutants does not cause ADE during heterologous challenge even though lower neutralizing Ab titers are generated by the mutant strains compared to the wild-type virus. To assess the safety (viremia profile) and efficacy (neutralizing antibody response and protection against challenge) of the 29-O-MTase mutant DENV vaccine approach in an immunologically competent host, three groups of Rhesus monkeys (RM) were immunized with different doses of E217A. These data demonstrate that live, attenuated DENV MTase mutant virus, even when administrated at low dose (1610 3 PFU), can induce protective immunity in non-human primates. cache = ./cache/cord-268677-ytxrrslz.txt txt = ./txt/cord-268677-ytxrrslz.txt === reduce.pl bib === id = cord-325326-2bbqz4o7 author = Beitzel, Brett F. title = High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing date = 2010-10-14 pages = extension = .txt mime = text/plain words = 7781 sentences = 388 flesch = 51 summary = We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. Toward this goal, we used transposon mutagenesis, reverse genetics, and fragment analysis by capillary electrophoresis to identify regions of the nsP3 gene that are important for replication and that result in temperature sensitive (ts) mutations. We used transposon mutagenesis to construct a cDNA library with small DNA fragments randomly inserted throughout the VEEV genome and then produced replication-competent virus through reverse genetics. Comparing transposon insertion sites in the resultant viruses to those in the starting library, we were able to produce a functional map of the entire genome of VEEV, and to identify several hundred potential ts mutations, including those we originally identified with the capillary electrophoresis method. cache = ./cache/cord-325326-2bbqz4o7.txt txt = ./txt/cord-325326-2bbqz4o7.txt === reduce.pl bib === id = cord-325624-6anybxnk author = Ireland, Derek D. C. title = RNase L Mediated Protection from Virus Induced Demyelination date = 2009-10-02 pages = extension = .txt mime = text/plain words = 8082 sentences = 397 flesch = 43 summary = The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. cache = ./cache/cord-325624-6anybxnk.txt txt = ./txt/cord-325624-6anybxnk.txt === reduce.pl bib === id = cord-325825-0lyt8gfq author = Griffiths, Samantha J. title = A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date = 2013-08-08 pages = extension = .txt mime = text/plain words = 12504 sentences = 601 flesch = 45 summary = Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). cache = ./cache/cord-325825-0lyt8gfq.txt txt = ./txt/cord-325825-0lyt8gfq.txt === reduce.pl bib === id = cord-325192-italbsed author = Desai, Tanay M. title = IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion date = 2014-04-03 pages = extension = .txt mime = text/plain words = 8249 sentences = 437 flesch = 51 summary = Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. Our results show that IFITM3 does not inhibit the lipid mixing stage of IAV fusion but blocks the release of viral contents into the cytosol, and that this phenotype does not correlate with cholesterol accumulation in intracellular compartments. Our results thus demonstrate that IFITM3 restricts the IAV fusion at a post-hemifusion step, most likely at the point of fusion pore opening, as evidenced by the dramatic decrease of the BlaM signal in A549 and MDCK cells expressing this protein (Fig. 1A ). Neither IAV lipid mixing (vDiD dequenching) nor fusion (BlaM signal) was inhibited by silencing NPC1 in A549 cells (Fig. 5E, F) . cache = ./cache/cord-325192-italbsed.txt txt = ./txt/cord-325192-italbsed.txt === reduce.pl bib === id = cord-324928-cpryxa6p author = Lello, Laura Sandra title = Cross-utilisation of template RNAs by alphavirus replicases date = 2020-09-04 pages = extension = .txt mime = text/plain words = 13762 sentences = 646 flesch = 50 summary = The differences between outgroup viruses and those belonging to the SFV complex had an impact on the design of the template RNAs. The 5' region of the CHIKV genome contains seven SL structures that affect genome replication in mammalian and/or mosquito cells [33] . Cross-utilisation of template RNAs by alphavirus replicases structures can be predicted for RNAs of other members of the SFV complex (S1 Fig), the 5' ends of the template RNAs of SFV, MAYV, RRV and ONNV had an identical design to that of the previously constructed CHIKV template, i.e. the 5' UTR was followed by 231nt encoding the N-terminus of nsP1 [43] . The levels of Fluc and Gluc expression in human cells, transfected with plasmids expressing template RNA and corresponding polymerase negative control replicase (P1234 GAA ), were similar for trans-replicases derived from different viruses and the same was observed for Ae albopictus cells. cache = ./cache/cord-324928-cpryxa6p.txt txt = ./txt/cord-324928-cpryxa6p.txt === reduce.pl bib === id = cord-331721-l5kocy4f author = Liang, Jingjing title = Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress date = 2017-01-11 pages = extension = .txt mime = text/plain words = 6595 sentences = 342 flesch = 54 summary = Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles. Indeed, we confirmed that hypothesis by first using co-IP to validate the specificity of the PPxY/WW-domain physical interaction between VP40 (both eVP40 and mVP40) and BAG3, and functionally demonstrated that expression of BAG3 inhibited VP40 VLP production, as well as budding of a VSV recombinant virus containing the EBOV VP40 PPxY L-domain motif. cache = ./cache/cord-331721-l5kocy4f.txt txt = ./txt/cord-331721-l5kocy4f.txt === reduce.pl bib === id = cord-331802-wo462anq author = Xia, Hongjie title = Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone date = 2015-07-28 pages = extension = .txt mime = text/plain words = 9410 sentences = 440 flesch = 50 summary = Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. Herein, we report that although bacterially expressed EV71 2C ATPase did not exhibit any RNA remodeling activity, eukaryotically expressed EV71 2C ATPase functions not only as an RNA helicase that unwinds RNA helices from 3 0 to 5 0 in an ATP-dependent manner but also as an RNA chaperone that destabilizes helices from either direction and facilitates strand annealing and complex RNA structure formation independently of ATP. cache = ./cache/cord-331802-wo462anq.txt txt = ./txt/cord-331802-wo462anq.txt === reduce.pl bib === id = cord-338053-8zlxsf1z author = Foo, Suan-Sin title = Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation date = 2015-02-19 pages = extension = .txt mime = text/plain words = 9156 sentences = 502 flesch = 51 summary = In summary, our data demonstrated the crucial role of PTX3 in modulating alphavirus-induced immune responses and disease manifestation through its N-terminal interaction with the virus particles leading to enhanced viral entry and replication. To confirm that the results of enhanced virus production was due to PTX3 enhancing RRV replication, HEK 293T cells transiently transfected with vector or hPTX3 plasmids were harvested at 20 hour post transfection (hpt) ( To further characterize the effect of PTX3 during alphaviral infection, we examined the potential of PTX3 to directly interact with the virus and enhance viral entry. To demonstrate that the effect of PTX3on enhancing RRV entry and replication contributed to the increased level of virus detected in the in vivo studies, we performed RRV infection on primary fibroblasts isolated from tails of PTX3 -/and WT C57BL/6 mice. cache = ./cache/cord-338053-8zlxsf1z.txt txt = ./txt/cord-338053-8zlxsf1z.txt === reduce.pl bib === id = cord-328947-3l9ydspz author = Webb, L. G. title = Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date = 2020-10-15 pages = extension = .txt mime = text/plain words = 9857 sentences = 544 flesch = 51 summary = CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . cache = ./cache/cord-328947-3l9ydspz.txt txt = ./txt/cord-328947-3l9ydspz.txt === reduce.pl bib === id = cord-332205-ydijp66b author = Hufsky, Franziska title = Virologists—Heroes need weapons date = 2018-02-08 pages = extension = .txt mime = text/plain words = 1165 sentences = 69 flesch = 53 summary = Nowadays, nearly everyone in the life sciences has used BLAST [8] at least once, or made an alignment, or asked a bioinformatician to analyze high-throughput sequencing data. Bioinformaticians routinely have to develop tailored, study-specific algorithms and tools used by a wide variety of scientists, including biochemists, biologists, geneticists, and molecular life scientists; but we rarely find virus-specific tools used by virologists. But astonishingly, we now know that the human genome consists of 8%-60% virus-derived sequences (depending on how this is measured: 8% can be directly traced back to viruses, whereas a figure of 60% includes LINEs and SINEs that are thought to be of viral origin [12] ). The EVBC aims to develop bioinformatical tools for nearly all areas: (1) for detection of viruses, e.g., from high-throughput sequencing data; (2) virus assembly; (3) quasispecies reconstruction; (4) intraviral interactions; (5) virus entry, i.e., protein-protein interaction; (6) virus -host interactions; (7) phylogeny/cophylogeny; and (8) therapy. cache = ./cache/cord-332205-ydijp66b.txt txt = ./txt/cord-332205-ydijp66b.txt === reduce.pl bib === === reduce.pl bib === id = cord-334315-ymkrgj0h author = Moon, Stephanie L. title = Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine date = 2013-12-05 pages = extension = .txt mime = text/plain words = 1995 sentences = 100 flesch = 43 summary = This review describes the myriad ways that viruses deal with the general host RNA decay machinery that is active in the cell immediately upon viral infection-turning what, at first, appears to be very hostile territory for a foreign transcript into a sort of ''promised land'' for viral gene expression. Disparate RNA viruses have, therefore, evolved unique mechanisms by which they disarm host RNA decay pathways by inactivating or proteolytically degrading important nucleases to promote productive viral infections. In addition, to make a cell more amenable to virus production, these virally encoded nucleases may also create a new ''sandbox'' in the cytoplasm for viral RNAs by initiating the large-scale decay of cellular mRNAs and dramatically altering the landscape of host gene expression. Considering the importance of RNA stability in regulating transcript abundance, the inactivation or commandeering of cellular RNA decay factors by viruses is likely to significantly alter host gene expression. cache = ./cache/cord-334315-ymkrgj0h.txt txt = ./txt/cord-334315-ymkrgj0h.txt === reduce.pl bib === === reduce.pl bib === id = cord-333473-c1lykari author = Irigoyen, Nerea title = High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling date = 2016-02-26 pages = extension = .txt mime = text/plain words = 18258 sentences = 844 flesch = 56 summary = Also, it has been employed in the study of the replication of large DNA viruses; namely, human cytomegalovirus [17] [18] , Kaposi's sarcoma-associated herpesvirus [19] , herpes simplex virus 1 [20] , vaccinia virus [21] , and bacteriophage lambda [22] , providing insights into the temporal regulation of gene expression in these viruses and identifying numerous previously unrecognized translated ORFs, including novel protein-coding ORFs and short regulatory uORFs. In this paper, we describe the first analysis of RNA virus replication and gene expression by ribosome profiling (and parallel RNASeq), using MHV as a model system. The latter are calculated on a per gene (rather than per transcript) basis, using RNASeq and RiboSeq reads contained entirely within annotated CDS regions (i.e. excluding 5 0 and 3 0 UTRs and also RPFs accumulating at or near to initiation or termination sites), and, like the virus values, are expressed relative to the mean levels for the cell (due to normalization by library size). cache = ./cache/cord-333473-c1lykari.txt txt = ./txt/cord-333473-c1lykari.txt === reduce.pl bib === id = cord-342291-imn7g084 author = Ciminski, Kevin title = Bats reveal the true power of influenza A virus adaptability date = 2020-04-16 pages = extension = .txt mime = text/plain words = 2478 sentences = 120 flesch = 50 summary = Indeed, the HA of the newly discovered Old World bat H9N2 virus binds to α2,3-sialic In contrast, the internal gene segments of the bat-derived IAVs form two outgroups that are located at a more basal position. Conventional IAVs and the bat H9N2 virus possess the surface glycoprotein neuraminidase (NA), which removes sialic acid residues from infected cells to facilitate the release of newly formed viral particles (Fig 2A) . The amazing ability of H18 to rapidly overcome the absence of a functional N11 suggests that the structure of H18 (and possibly H17) may provide a broader scope of evolutionary flexibility than that of conventional sialic acid-dependent IAVs. It is therefore tempting to speculate that bat IAV HA proteins, and in particular H18, might have the potential to adapt to novel and so far unknown entry receptors different from MHC-II (Fig 2D) . cache = ./cache/cord-342291-imn7g084.txt txt = ./txt/cord-342291-imn7g084.txt === reduce.pl bib === id = cord-338400-30vl2hks author = Epstein, Jonathan H. title = Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh date = 2010-07-01 pages = extension = .txt mime = text/plain words = 4653 sentences = 246 flesch = 50 summary = Phylogenetic analysis indicates that this first GBV-like flavivirus reported in bats constitutes a distinct species within the Flaviviridae family and is ancestral to the GBV-A and -C virus clades. GBV-A viruses have been described in New World primates and are not known to infect humans [17] [18] [19] , while GBV-C (also known as Hepatitis G virus (HGV)) have frequently been isolated from humans in many regions of the World, including India and Bangladesh [19] [20] [21] [22] [23] , and from wild chimpanzees (Pan troglodytes) in Africa [24, 25] . Our findings provide new insight into the range of known hosts for GB-like viruses and demonstrate the power of unbiased sequencing to characterize the diversity of potentially zoonotic pathogens carried by bats and other reservoirs. Molecular analyses of sera from Pteropus giganteus bats from Faridpur, Bangladesh led to the identification of a 9,633 nt sequence consistent in genomic organization with known GBV and other species within the family Flaviviridae [16] . cache = ./cache/cord-338400-30vl2hks.txt txt = ./txt/cord-338400-30vl2hks.txt === reduce.pl bib === id = cord-348799-qu4zin3o author = Wu, Nannan title = The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation date = 2019-10-10 pages = extension = .txt mime = text/plain words = 11391 sentences = 520 flesch = 48 summary = This lack of specificity was not present in cells however, given that the ectopic expression of ISG20 did not lead to the indiscriminate degradation of cellular RNAs (ribosomal as well as small nucleolar RNAs previously shown to be associated to ISG20 [2] ), nor of an Hepatitis C virus (HCV)-derived Luciferase reporter mRNA produced in vitro and then transfected into cells (S4C and S4D Fig) , suggesting that in cells the RNase activity of ISG20 is tightly controlled. Self mimicry allows the escape of target genes' mRNAs from the effects of ISG20 VSV infection and ectopic DNA or RNA transfection do not bear much in common apart from the fact that both represent artificial injections into the cell of non-self genetic material from without. To further determine whether ISG20 acted on translation initiation and more specifically through specific initiation factors (eIFs), capped and polyadenylated mRNAs coding luciferase under the control of several 5' untranslated regions (5' UTRs) were generated in vitro and directly transfected in ISG20-expressing cells (Fig 3D) . cache = ./cache/cord-348799-qu4zin3o.txt txt = ./txt/cord-348799-qu4zin3o.txt === reduce.pl bib === id = cord-342825-s8ddek2f author = Kim, Ye Ji title = Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators date = 2016-08-26 pages = extension = .txt mime = text/plain words = 10236 sentences = 535 flesch = 49 summary = RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. This result suggests that an indirect effect of virus infection on neighboring uninfected cells is responsible for the greater induction of ISG15 and protein ISGylation by HCMV than by UV-HCMV at low MOIs. Since HCMV IE1 inhibits the activation of ISRE-containing promoters by sequestering STAT2 [58] [59] [60] and PML [61] , IE1 expression may be responsible for the suppression of free ISG15 and ISG15 conjugate levels during HCMV infection. In addition to IE1, the presence of additional viral functions that downregulate protein ISGylation was prompted by our observation that UV-HCMV infection resulted in a higher level of ISG15 conjugates than IE1-deleted mutant virus at late times (Fig 2B) . cache = ./cache/cord-342825-s8ddek2f.txt txt = ./txt/cord-342825-s8ddek2f.txt === reduce.pl bib === id = cord-355610-7xy4s483 author = Hu, Dan title = A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III date = 2019-06-26 pages = extension = .txt mime = text/plain words = 6168 sentences = 307 flesch = 52 summary = Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate. Its fully human origin, the germline-like nature, combined with high-affinity and broad neutralizing activity toward all DENV serotypes, suggest that m366.6 is a promising candidate antiviral agent and may also provide a unique template for designing effective dengue vaccine immunogens. Two antibodies, designated as m360 and m366, bound potently to DENV DIIIs. Their scFv gene were fused with human IgG1 Fc for protein expression, and surface plasmon resonance (SPR) experiments were used to evaluate the antigens binding. cache = ./cache/cord-355610-7xy4s483.txt txt = ./txt/cord-355610-7xy4s483.txt === reduce.pl bib === id = cord-353353-njvalb44 author = Lau, Susanna K. P. title = Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model date = 2016-10-13 pages = extension = .txt mime = text/plain words = 6982 sentences = 314 flesch = 44 summary = Analysis of 13 complete genome sequences showed that "Rosavirus B" and "Rosavirus C" represent two potentially novel picornavirus species infecting different rodents. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Rosavirus C isolated from cell culture causes multisystemic diseases in a mouse model, with histopathological changes and positive viral antigen expression in lungs and liver of infected mice. A total of 13 complete genomes from samples of four different wild rodent species (chestnut spiny rat, Coxing's white-bellied rat, roof rat and Indochinese forest rat) positive for "Rosavirus C" and one street rodent species (Norway rat) positive for "Rosavirus B" were sequenced directly from the positive respiratory or alimentary samples and characterized. Infected cell lines and tissues from challenged mice that were tested positive for rosavirus C RASM14A by RT-PCR were subject to viral load studies and immunohistochemical staining for viral VP1 protein as described previously [28, 69] . cache = ./cache/cord-353353-njvalb44.txt txt = ./txt/cord-353353-njvalb44.txt === reduce.pl bib === === reduce.pl bib === id = cord-353337-o302vxqm author = Visser, Linda J. title = Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date = 2020-07-15 pages = extension = .txt mime = text/plain words = 9547 sentences = 514 flesch = 54 summary = To study the effects of L pro on the induction of type I IFN in picornavirus-infected cells, we used two previously generated recombinant viruses; EMCV-L Zn , which contains inactivating mutations in the zinc-finger domain of the Leader (i.e. EMCV's RLR signaling antagonist) [1, 43, 44] , and EMCV-L pro , which was derived from EMCV-L Zn and additionally encodes FMDV L pro at the N-terminus of its polyprotein ( Fig 1A) [45]. Cleavage of RLR signaling proteins by FMDV L pro correlates with type I IFN suppression degradation of NF-κB p65 and DUB activity as well as to impair L pro 's ability to reduce IFN-β mRNA expression [36, 39] , also affected L pro 's ability to cleave MAVS and TBK1. Notably, infection with EMCV L pro L143A, which displayed wt deISGylase/DUB activity but is strongly impaired in its ability to cleave/degrade RLR signaling proteins MAVS, TBK1 and NFκB p65, failed to suppress the induction of IFN-β mRNA. cache = ./cache/cord-353337-o302vxqm.txt txt = ./txt/cord-353337-o302vxqm.txt === reduce.pl bib === id = cord-334947-pa0p5dif author = Rozen-Gagnon, Kathryn title = Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models date = 2014-01-16 pages = extension = .txt mime = text/plain words = 8887 sentences = 415 flesch = 44 summary = Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. To estimate the population diversity of variants by deep sequencing, cDNA libraries were prepared by Superscript III from RNA extracted from virus generated in BHK-21 or C6/36 cells, and the viral genome was amplified using a high fidelity polymerase (Phusion) to generate 5 overlapping amplicons 2-3 kb in length. To address the possibility that the fitness cost of defective replication, observed in mosquito cell culture, would favor the reversion of these mutant polymerases to wildtype, we deep sequenced virus from the body of an individual mosquito that presented the median titer from each group. cache = ./cache/cord-334947-pa0p5dif.txt txt = ./txt/cord-334947-pa0p5dif.txt === reduce.pl bib === id = cord-351389-48tszqh5 author = Xu, Kai title = Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody date = 2013-10-10 pages = extension = .txt mime = text/plain words = 6688 sentences = 280 flesch = 50 summary = title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. We used X-ray crystallography to determine the high-resolution structures of the Hendra virus G glycoprotein in complex with a cross-reactive neutralizing human monoclonal antibody. Taken together, the success of hmAb m102.4 in vivo as an effective post-exposure treatment against henipavirus disease in two different well-characterized animal models (the ferret and nonhuman primate), along with the new detailed structural findings on its viral G glycoprotein binding features that help explain its superior cross-reactive neutralizing activity, will facilitate efforts aimed at obtaining approved human use application to treat accidental exposure to HeV or NiV infection. cache = ./cache/cord-351389-48tszqh5.txt txt = ./txt/cord-351389-48tszqh5.txt === reduce.pl bib === id = cord-355839-o0m71kvw author = Sedeyn, Koen title = Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date = 2019-10-17 pages = extension = .txt mime = text/plain words = 8187 sentences = 414 flesch = 45 summary = ATF2, activating transcription factor 2; CDS, cytoplasmic DNA sensor; ER, endoplasmic reticulum; IFN, interferon; IKK, inhibitor of nuclear factor kappa-B kinase; IKKε, inhibitor of nuclear factor kappa-B kinase subunit epsilon; IRF3, interferon regulatory factor 3; IRF7, interferon regulatory factor 7; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAVS, mitochondrial antiviral-signaling protein; MDA5, melanoma differentiation-associated protein 5; MyD88, myeloid differentiation primary response protein MyD88; NF-kB, nuclear factor-kappa B; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PAMP, pathogenassociated molecular pattern; PRR, pattern recognition receptor; RIG, retinoic-acid-inducible gene-I; RLR, RIG-I-like receptor; RSV, respiratory syncytial virus; STING, stimulator of interferon protein; TBK1, tank binding kinase 1; TICAM1, toll/interleukin-1 receptor domain-containing adapter molecule 1; TIRAP, toll/ interleukin-1 receptor domain-containing adapter protein; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptor-associated factor 3; TRAF6, tumor necrosis factor receptor-associated factor 6; TRAM, toll-like receptor adaptor molecule. cache = ./cache/cord-355839-o0m71kvw.txt txt = ./txt/cord-355839-o0m71kvw.txt === reduce.pl bib === === reduce.pl bib === id = cord-346053-mk1mzc5z author = Morris, Cindy E. title = Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries date = 2009-12-24 pages = extension = .txt mime = text/plain words = 4758 sentences = 262 flesch = 39 summary = We present numerous examples of virulence traits in plant pathogenic microorganisms that also have a function in their survival and growth in nonagricultural and nonplant habitats. Adaptation to biotic and abiotic stresses, within or outside of agricultural habitats, likely plays as important a role in the evolution of parasitic fitness of plant pathogens as it does for human pathogens. As illustrated above, traits that confer fitness in response to biotic and abiotic environmental stress can have dual-use as virulence factors in human pathogens. In plant pathogens, the transport systems for toxins and antimicrobials can have broad spectrum activity, leading to resistance to agricultural fungicides and also contributing to virulence [12] . The examples listed above that describe traits that play roles in both environmental fitness and virulence to plants provide a compelling incentive to expand our paradigms concerning the forces that drive evolution of plant pathogenicity. cache = ./cache/cord-346053-mk1mzc5z.txt txt = ./txt/cord-346053-mk1mzc5z.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-351548-jvl63652 author = Juranic Lisnic, Vanda title = Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date = 2013-09-26 pages = extension = .txt mime = text/plain words = 11978 sentences = 623 flesch = 49 summary = Finally, a recent transcriptomic analysis of newly synthesized RNA in MCMV infected fibroblasts [15] applied RNA-Seq technology to study regulation of viral gene expression and identified a very early peak of viral gene transcriptional activity at 1-2 hours post infection followed by rapid cellular countermeasures but did not attempt to re-annotate MCMV genome. The MCMV transcripts identified through our classical cDNA cloning and sequencing (green arrows) and the RNA-Seq expression profiles (gray histograms), showed complementary results to each other but diverged dramatically from current annotations. Because cDNA cloning and RNA-Seq identified significant differences between the MCMV transcriptome and current annotations, we performed an in depth analysis of several genomic regions by northern analyses ( Figure 5 , Figures S2, S3 , S4, S5) using our cDNA clones to generate strand specific riboprobes ( Table 1) . cache = ./cache/cord-351548-jvl63652.txt txt = ./txt/cord-351548-jvl63652.txt === reduce.pl bib === id = cord-343221-e29of29o author = Kindler, Eveline title = Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date = 2017-02-03 pages = extension = .txt mime = text/plain words = 7896 sentences = 423 flesch = 51 summary = Specifically, we show that genetically engineered mutants of mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E), respectively, that encode an EndoU active-site substitution known to abolish nucleolytic activity, were severely attenuated and elicited an immediate and simultaneous activation of host cell dsRNA sensors. The severe attenuation of MHV H277A and HCoV-229E H250A replication in wild-type murine and human macrophages, respectively, precluded the use of primary macrophages to assess the sensitivity of EndoU-deficient coronaviruses to IFN-I pre-treatment. Our data suggest that direct restriction of replication of EndoU-deficient coronaviruses is mediated by RNase L-mediated RNA degradation and inhibition of host cell translation through activation of PKR. Notably, also in this case Xrn1 is required to further process the de-capped mRNAs. Our data show that early during coronavirus infection the EndoU activity conceptually fulfils the same task, namely the removal of dsRNA that would otherwise trigger host cell dsRNA responses, such as IFN-β expression and activation of PKR and OAS/RNase L. cache = ./cache/cord-343221-e29of29o.txt txt = ./txt/cord-343221-e29of29o.txt === reduce.pl bib === ===== Reducing email addresses Creating transaction Updating adr table ===== Reducing keywords parallel: Warning: Only enough available processes to run 20 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. cord-000018-amvlm09p cord-000007-h8upyzb1 cord-000232-boto4h8x cord-000318-wk2u2a9w parallel: Warning: No more processes: Decreasing number of running jobs to 19. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. cord-258234-qn8xp4v9 cord-004428-ob5igsv5 cord-000933-nn9gj0z1 cord-262248-q5eijunp cord-003982-7v5xl1s3 cord-280621-tph5n7ak cord-001636-khrx6rnh cord-000127-tkxpjlyn cord-000409-lpf9lpky cord-001257-t21l6i3f cord-000005-zt6i3o86 cord-000729-iq30z094 cord-001769-2sdg5ll7 cord-001859-d62iuk72 cord-002542-f7l4ty2j cord-302340-pw2xqhwa cord-269466-9hnal9ad cord-290253-hxxizipk cord-001700-c6elsnag cord-268388-kkhuzf3p cord-266078-h53zpjab cord-003441-810r5q03 cord-002423-1u44tdrj cord-304815-3datxv8j cord-262753-jld1ygxt cord-000103-3zh8jmc2 cord-001109-xs7df6a7 cord-253783-3a1qde41 cord-277566-j3ehiwn9 cord-287219-qxkwjkif cord-001676-68y733y3 cord-002835-qaogpxy9 cord-297702-vxcj25sn cord-000246-mlhd9zbs cord-000025-6zrv687k cord-290617-45be6gxe cord-001992-m4k20i7g cord-002608-zn7tm1ww cord-315316-w7cn9iqp cord-002142-tdgu9sr9 cord-002893-d7hetoq0 cord-076082-4kpkhz0o cord-278511-je1509ar cord-312743-9e4yufo5 cord-280221-s6oxq772 cord-316999-712rit8h cord-286072-kgpvdb42 cord-001541-5d64esp4 cord-321874-eenaixp0 cord-275307-d7htyfcl cord-265947-7j9qqi8w cord-000164-094d0rn6 cord-002530-ao7kenbx cord-001655-uqw74ra0 cord-286137-4cbh3u3z cord-343221-e29of29o cord-356115-vblgotjn cord-000354-05lnj3w0 cord-311383-1aqt65cc cord-288231-vg8bwed9 cord-281404-5a8au32c cord-278569-yr06jwm1 cord-013481-3zwq67do cord-314451-mqnqjn0c cord-013526-6fip93l2 cord-289879-fh7ic0kp cord-254735-8reu45yz cord-000578-jhetyd9t cord-271692-60nlid3c cord-316584-b1aa1lri cord-292424-daj4zcm1 cord-294342-7ycgd0h7 cord-003169-bdw5ke4i cord-002706-m3y35ozx cord-011380-kfkp1zpn cord-321957-ybtk9cp1 cord-010762-c01wgg4v cord-001385-rb5vwolt cord-306624-1mjmttec cord-260949-w2xuf15h cord-264225-vzcfeh7t cord-260729-b12v3c8c cord-267149-5twx9y5c cord-309056-ul9q3ebx cord-001082-sufwsu77 cord-293164-i50cgkvq cord-263239-andje0wu cord-000660-tsvzg0ax cord-002125-anp238gu cord-310509-c8wp2m69 cord-304747-ojyxs3cp cord-325825-0lyt8gfq cord-324928-cpryxa6p cord-331721-l5kocy4f cord-323568-s0wmll4q cord-331802-wo462anq cord-325192-italbsed cord-338053-8zlxsf1z cord-264579-csro48ks cord-325624-6anybxnk cord-325326-2bbqz4o7 cord-353337-o302vxqm cord-351389-48tszqh5 cord-353353-njvalb44 cord-353703-u86ggw11 cord-351952-lhhjax3s cord-351548-jvl63652 cord-334947-pa0p5dif cord-332205-ydijp66b cord-334315-ymkrgj0h cord-342291-imn7g084 cord-348799-qu4zin3o cord-328947-3l9ydspz cord-333473-c1lykari cord-350640-sz6xj5o3 cord-346053-mk1mzc5z cord-355839-o0m71kvw cord-268677-ytxrrslz cord-338400-30vl2hks cord-342419-liaihahj cord-341034-2oigu75k cord-342825-s8ddek2f cord-332747-u46xryoo cord-355610-7xy4s483 cord-303403-9th2jiq6 Creating transaction Updating wrd table ===== Reducing urls cord-000007-h8upyzb1 cord-290617-45be6gxe cord-002542-f7l4ty2j cord-001541-5d64esp4 cord-312743-9e4yufo5 cord-003441-810r5q03 cord-002893-d7hetoq0 cord-003982-7v5xl1s3 cord-262753-jld1ygxt cord-304815-3datxv8j cord-254735-8reu45yz cord-297702-vxcj25sn cord-004428-ob5igsv5 cord-292424-daj4zcm1 cord-265947-7j9qqi8w cord-002835-qaogpxy9 cord-253783-3a1qde41 cord-002608-zn7tm1ww cord-011380-kfkp1zpn cord-002530-ao7kenbx cord-001655-uqw74ra0 cord-013481-3zwq67do cord-001992-m4k20i7g cord-286072-kgpvdb42 cord-302340-pw2xqhwa cord-013526-6fip93l2 cord-321957-ybtk9cp1 cord-002706-m3y35ozx cord-002125-anp238gu cord-010762-c01wgg4v cord-260949-w2xuf15h cord-321874-eenaixp0 cord-260729-b12v3c8c cord-314451-mqnqjn0c cord-268677-ytxrrslz cord-324928-cpryxa6p cord-323568-s0wmll4q cord-328947-3l9ydspz cord-332747-u46xryoo cord-351389-48tszqh5 cord-353337-o302vxqm cord-334947-pa0p5dif cord-338400-30vl2hks cord-351952-lhhjax3s cord-333473-c1lykari cord-355610-7xy4s483 cord-351548-jvl63652 cord-355839-o0m71kvw cord-342419-liaihahj cord-353703-u86ggw11 cord-331802-wo462anq cord-348799-qu4zin3o cord-304747-ojyxs3cp Creating transaction Updating url table ===== Reducing named entities cord-002893-d7hetoq0 cord-280621-tph5n7ak cord-000232-boto4h8x cord-004428-ob5igsv5 cord-000005-zt6i3o86 cord-000127-tkxpjlyn cord-000318-wk2u2a9w cord-001109-xs7df6a7 cord-000025-6zrv687k cord-290617-45be6gxe cord-258234-qn8xp4v9 cord-000409-lpf9lpky cord-001257-t21l6i3f cord-000164-094d0rn6 cord-003982-7v5xl1s3 cord-000007-h8upyzb1 cord-001541-5d64esp4 cord-001859-d62iuk72 cord-000933-nn9gj0z1 cord-262248-q5eijunp cord-312743-9e4yufo5 cord-001636-khrx6rnh cord-000729-iq30z094 cord-000018-amvlm09p cord-003441-810r5q03 cord-269466-9hnal9ad cord-001700-c6elsnag cord-266078-h53zpjab cord-002835-qaogpxy9 cord-287219-qxkwjkif cord-302340-pw2xqhwa cord-278511-je1509ar cord-002423-1u44tdrj cord-290253-hxxizipk cord-076082-4kpkhz0o cord-297702-vxcj25sn cord-001676-68y733y3 cord-304815-3datxv8j cord-002542-f7l4ty2j cord-000103-3zh8jmc2 parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. cord-001769-2sdg5ll7 cord-001992-m4k20i7g cord-000246-mlhd9zbs parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. cord-265947-7j9qqi8w cord-253783-3a1qde41 cord-002608-zn7tm1ww cord-002142-tdgu9sr9 cord-262753-jld1ygxt cord-000354-05lnj3w0 cord-281404-5a8au32c cord-292424-daj4zcm1 cord-321874-eenaixp0 cord-268388-kkhuzf3p cord-280221-s6oxq772 cord-306624-1mjmttec cord-013526-6fip93l2 cord-013481-3zwq67do cord-288231-vg8bwed9 cord-001655-uqw74ra0 cord-003169-bdw5ke4i cord-001385-rb5vwolt cord-254735-8reu45yz cord-286072-kgpvdb42 cord-311383-1aqt65cc cord-002530-ao7kenbx cord-315316-w7cn9iqp cord-278569-yr06jwm1 cord-286137-4cbh3u3z cord-011380-kfkp1zpn cord-277566-j3ehiwn9 cord-010762-c01wgg4v cord-275307-d7htyfcl cord-316999-712rit8h cord-314451-mqnqjn0c cord-271692-60nlid3c cord-321957-ybtk9cp1 cord-000578-jhetyd9t cord-293164-i50cgkvq cord-316584-b1aa1lri cord-001082-sufwsu77 cord-260949-w2xuf15h cord-294342-7ycgd0h7 cord-263239-andje0wu cord-310509-c8wp2m69 cord-000660-tsvzg0ax cord-309056-ul9q3ebx cord-304747-ojyxs3cp cord-323568-s0wmll4q cord-264579-csro48ks cord-303403-9th2jiq6 cord-002706-m3y35ozx cord-267149-5twx9y5c cord-325825-0lyt8gfq cord-325326-2bbqz4o7 cord-325192-italbsed cord-002125-anp238gu cord-334315-ymkrgj0h cord-342825-s8ddek2f cord-342291-imn7g084 cord-350640-sz6xj5o3 cord-338400-30vl2hks cord-332205-ydijp66b cord-264225-vzcfeh7t cord-332747-u46xryoo cord-356115-vblgotjn cord-346053-mk1mzc5z cord-338053-8zlxsf1z cord-342419-liaihahj cord-331721-l5kocy4f cord-351952-lhhjax3s cord-351389-48tszqh5 cord-289879-fh7ic0kp cord-333473-c1lykari cord-343221-e29of29o cord-355610-7xy4s483 cord-328947-3l9ydspz cord-353337-o302vxqm cord-268677-ytxrrslz cord-260729-b12v3c8c cord-325624-6anybxnk cord-355839-o0m71kvw cord-351548-jvl63652 cord-353703-u86ggw11 cord-331802-wo462anq cord-334947-pa0p5dif cord-324928-cpryxa6p cord-348799-qu4zin3o cord-353353-njvalb44 cord-341034-2oigu75k Creating transaction Updating ent table ===== Reducing parts of speech parallel: Warning: No more processes: Decreasing number of running 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cord-001859-d62iuk72 cord-076082-4kpkhz0o cord-287219-qxkwjkif cord-266078-h53zpjab cord-253783-3a1qde41 cord-000318-wk2u2a9w cord-001992-m4k20i7g cord-297702-vxcj25sn parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. cord-000246-mlhd9zbs cord-010762-c01wgg4v cord-002142-tdgu9sr9 cord-002608-zn7tm1ww cord-275307-d7htyfcl cord-321874-eenaixp0 cord-000354-05lnj3w0 cord-268388-kkhuzf3p cord-254735-8reu45yz cord-265947-7j9qqi8w cord-292424-daj4zcm1 cord-001655-uqw74ra0 cord-280221-s6oxq772 cord-286137-4cbh3u3z cord-277566-j3ehiwn9 cord-281404-5a8au32c cord-315316-w7cn9iqp cord-002530-ao7kenbx cord-001385-rb5vwolt cord-288231-vg8bwed9 cord-311383-1aqt65cc cord-316999-712rit8h cord-013526-6fip93l2 cord-271692-60nlid3c cord-003169-bdw5ke4i cord-013481-3zwq67do cord-306624-1mjmttec cord-286072-kgpvdb42 cord-278569-yr06jwm1 cord-314451-mqnqjn0c cord-289879-fh7ic0kp cord-000578-jhetyd9t cord-321957-ybtk9cp1 cord-309056-ul9q3ebx cord-316584-b1aa1lri cord-293164-i50cgkvq cord-002706-m3y35ozx cord-011380-kfkp1zpn cord-264225-vzcfeh7t cord-294342-7ycgd0h7 cord-002125-anp238gu cord-260729-b12v3c8c cord-267149-5twx9y5c cord-000660-tsvzg0ax cord-260949-w2xuf15h cord-310509-c8wp2m69 cord-001082-sufwsu77 cord-263239-andje0wu cord-304747-ojyxs3cp cord-264579-csro48ks cord-323568-s0wmll4q cord-268677-ytxrrslz cord-325326-2bbqz4o7 cord-325192-italbsed cord-342291-imn7g084 cord-324928-cpryxa6p cord-341034-2oigu75k cord-342825-s8ddek2f cord-348799-qu4zin3o cord-353337-o302vxqm cord-332205-ydijp66b cord-353353-njvalb44 cord-351389-48tszqh5 cord-333473-c1lykari cord-355610-7xy4s483 cord-351548-jvl63652 cord-338053-8zlxsf1z cord-350640-sz6xj5o3 cord-355839-o0m71kvw cord-343221-e29of29o cord-356115-vblgotjn cord-342419-liaihahj cord-346053-mk1mzc5z cord-334947-pa0p5dif cord-332747-u46xryoo cord-334315-ymkrgj0h cord-351952-lhhjax3s cord-338400-30vl2hks cord-331721-l5kocy4f cord-331802-wo462anq cord-328947-3l9ydspz cord-353703-u86ggw11 cord-303403-9th2jiq6 cord-325825-0lyt8gfq cord-325624-6anybxnk Creating transaction Updating pos table Building ./etc/reader.txt cord-324928-cpryxa6p cord-000933-nn9gj0z1 cord-333473-c1lykari cord-353337-o302vxqm cord-000018-amvlm09p cord-355839-o0m71kvw number of items: 129 sum of words: 528,154 average size in words: 7,766 average readability score: 48 nouns: virus; cells; infection; protein; cell; replication; viruses; proteins; expression; mice; host; data; activity; analysis; type; gene; receptor; levels; influenza; response; fusion; role; genome; control; entry; sequence; results; particles; genes; coronavirus; membrane; activation; antibody; studies; site; structure; time; ml; disease; antibodies; study; species; assay; samples; region; interaction; synthesis; dna; domain; presence verbs: used; shows; bind; infected; containing; indicate; determining; induced; observed; suggest; followed; described; expressed; including; increasing; performed; compared; required; identify; inhibits; found; associated; detected; mediate; reduced; provide; result; demonstrated; reveal; generate; based; treated; signaling; incubated; encode; involved; report; known; led; obtained; purified; affected; analyzed; transfected; regulates; activating; occur; caused; produced; targeting adjectives: viral; human; specific; different; cellular; anti; immune; infected; similar; non; high; dependent; antiviral; infectious; structural; respiratory; significant; wild; important; low; recombinant; single; functional; like; several; negative; new; positive; multiple; severe; novel; total; primary; molecular; essential; independent; small; early; acute; relative; higher; additional; present; many; first; innate; clinical; consistent; mutant; genomic adverbs: also; however; previously; well; respectively; significantly; highly; therefore; interestingly; together; directly; prior; furthermore; first; likely; even; moreover; recently; less; efficiently; nt; subsequently; specifically; similarly; approximately; strongly; indeed; relatively; briefly; still; rather; next; importantly; later; finally; least; currently; notably; potentially; closely; clearly; alone; often; partially; completely; overnight; yet; fully; much; twice pronouns: we; it; their; our; its; i; they; them; us; his; itself; ifitm3; themselves; one; you; isg20; imagej; mrnas; had37; he; rad5; pdcs; her; orf16; mg; isgf3; hek-293ts; his3d1; egfp; ™; yourself; your; yjbh.; wt/; usp21; type-; she; s230; s; rptx3; rps11; rhptx3; rad5-hdpp4-shcd9; r170h; pro507; pp38-gfp; pcdna3.1-ace2-c9; p9-met; p62; ourselves proper nouns: Fig; RNA; IFN; SARS; C; T; MHV; PCR; CoV; L; HA; PBS; HCV; EV71; WT; A; S1; NA; VSV; F; S; Table; IAV; RSV; D; HIV-1; CHIKV; M; G; CD8; B; MOI; RT; pH; mRNA; S2; Figure; GFP; Virus; N; ATPase; WNV; K; GP; NP; HIV; p.i; DI; PTX3; CD4 keywords: rna; ifn; virus; cell; sars; mhv; dna; protein; viral; tcr; stat1; sinv; rsv; mers; iav; host; hiv-1; hcv; gfp; gene; ev71; ebola; cov; chikv; cd8; cd4; a59; wnv; vsv; veev; tmprss2; tbsv; sting; specie; pr8; pcr; pbs; pathogen; orf; nipah; mhv-3; mdck; ifitm3; ie1; human; hcmv; h5n1; golgi; fhv; fgl2 one topic; one dimension: virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572141/ titles(s): Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression three topics; one dimension: cells; virus; virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654589/, https://www.ncbi.nlm.nih.gov/pubmed/26919232/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990711/ titles(s): Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments | High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling | The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication five topics; three dimensions: rna virus viral; cells virus protein; virus mice cells; cells protein virus; cells fusion cell file(s): https://www.ncbi.nlm.nih.gov/pubmed/26919232/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806877/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855438/, https://www.ncbi.nlm.nih.gov/pubmed/19119424/, https://doi.org/10.1371/journal.ppat.1005373 titles(s): High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling | The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles | Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring | The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution | Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger Type: cord title: journal-plosPathog-cord date: 2021-05-30 time: 15:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"PLoS Pathog" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-267149-5twx9y5c author: Abraham, Jonathan title: Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses date: 2009-04-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens. url: https://doi.org/10.1371/journal.ppat.1000358 doi: 10.1371/journal.ppat.1000358 id: cord-269466-9hnal9ad author: Agbeci, Maxime title: Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus date: 2013-10-03 words: 7184.0 sentences: 391.0 pages: flesch: 49.0 cache: ./cache/cord-269466-9hnal9ad.txt txt: ./txt/cord-269466-9hnal9ad.txt summary: In this study, we used a novel dual gene cassette construct that differentiated primary infected cells from cells infected after virus intercellular movement to show that the early as well as the late secretory pathway, but not endocytosis, was important for TuMV transport. By using a dual cassette of genes encoding fluorescent proteins that can differentiate between primary infected cells and cells infected after intercellular transport, we provide evidence that turnip mosaic virus (TuMV) needs a functional secretory pathway where pre-and post-Golgi trafficking and the actomyosin network are important for its movement. Fig. 2E shows that that there was no significant difference in the ratio of red over green fluorescence during BFA and CMA treatments compared with the no inhibitor treatment (TuMV alone) at 4 dpinf, indicating that viral protein production in the primary infected cells was not affected by the drug treatments. abstract: The contribution of different host cell transport systems in the intercellular movement of turnip mosaic virus (TuMV) was investigated. To discriminate between primary infections and secondary infections associated with the virus intercellular movement, a gene cassette expressing GFP-HDEL was inserted adjacent to a TuMV infectious cassette expressing 6K(2):mCherry, both within the T-DNA borders of the binary vector pCambia. In this system, both gene cassettes were delivered to the same cell by a single binary vector and primary infection foci emitted green and red fluorescence while secondarily infected cells emitted only red fluorescence. Intercellular movement was measured at 72 hours post infiltration and was estimated to proceed at an average rate of one cell being infected every three hours over an observation period of 17 hours. To determine if the secretory pathway were important for TuMV intercellular movement, chemical and protein inhibitors that blocked both early and late secretory pathways were used. Treatment with Brefeldin A or Concanamycin A or expression of ARF1 or RAB-E1d dominant negative mutants, all of which inhibit pre- or post-Golgi transport, reduced intercellular movement by the virus. These treatments, however, did not inhibit virus replication in primary infected cells. Pharmacological interference assays using Tyrphostin A23 or Wortmannin showed that endocytosis was not important for TuMV intercellular movement. Lack of co-localization by endocytosed FM4-64 and Ara7 (AtRabF2b) with TuMV-induced 6K(2)-tagged vesicles further supported this conclusion. Microfilament depolymerizing drugs and silencing expression of myosin XI-2 gene, but not myosin VIII genes, also inhibited TuMV intercellular movement. Expression of dominant negative myosin mutants confirmed the role played by myosin XI-2 as well as by myosin XI-K in TuMV intercellular movement. Using this dual gene cassette expression system and transport inhibitors, components of the secretory and actomyosin machinery were shown to be important for TuMV intercellular spread. url: https://www.ncbi.nlm.nih.gov/pubmed/24098128/ doi: 10.1371/journal.ppat.1003683 id: cord-001859-d62iuk72 author: Baquero-Pérez, Belinda title: Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date: 2015-11-20 words: 15958.0 sentences: 876.0 pages: flesch: 50.0 cache: ./cache/cord-001859-d62iuk72.txt txt: ./txt/cord-001859-d62iuk72.txt summary: Similar Hsc70 localization was seen during early lytic replication (12 h reactivation), when RTA protein was diffuse in the nucleus, Successful enrichment of the nuclear envelope region and associated KSHV RTCs in HEK-293T rKSHV.219 cells. These results clearly demonstrate that KSHV specifically redistributes the molecular chaperones, Hsc70 and iHsp70, from the cytoplasm to the nucleus, in contrast to Grp78, which coincides with the initial formation of KSHV RTCs. Treatment with the small molecule inhibitor VER-155008 abrogated viral protein synthesis at non-cytotoxic concentrations Members of the HSP70 chaperone family possess an N-terminal nucleotide binding domain with ATPase activity which is essential for their function. Therefore to ascertain whether Hsp70 isoforms could stabilise the essential KSHV lytic proteins RTA and ORF57, TREx BCBL1-RTA cells were reactivated for 24 h to allow sufficient viral protein expression followed by addition of DMSO control or VER-155008 in conjunction with cycloheximide (CHX) at 50 μg/ml to block de novo protein synthesis. abstract: Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654589/ doi: 10.1371/journal.ppat.1005274 id: cord-325326-2bbqz4o7 author: Beitzel, Brett F. title: High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing date: 2010-10-14 words: 7781.0 sentences: 388.0 pages: flesch: 51.0 cache: ./cache/cord-325326-2bbqz4o7.txt txt: ./txt/cord-325326-2bbqz4o7.txt summary: We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. Toward this goal, we used transposon mutagenesis, reverse genetics, and fragment analysis by capillary electrophoresis to identify regions of the nsP3 gene that are important for replication and that result in temperature sensitive (ts) mutations. We used transposon mutagenesis to construct a cDNA library with small DNA fragments randomly inserted throughout the VEEV genome and then produced replication-competent virus through reverse genetics. Comparing transposon insertion sites in the resultant viruses to those in the starting library, we were able to produce a functional map of the entire genome of VEEV, and to identify several hundred potential ts mutations, including those we originally identified with the capillary electrophoresis method. abstract: We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system. url: https://doi.org/10.1371/journal.ppat.1001146 doi: 10.1371/journal.ppat.1001146 id: cord-000005-zt6i3o86 author: Bischof, Larry J. title: Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo date: 2008-10-10 words: 7600.0 sentences: 401.0 pages: flesch: 56.0 cache: ./cache/cord-000005-zt6i3o86.txt txt: ./txt/cord-000005-zt6i3o86.txt summary: elegans and mammalian cells to PFTs. We demonstrate for the first time that the ire-1 -xbp-1 arm of the UPR (and to a lesser extent the atf-6 arm) is functionally important for defense against a pathogenic attack since loss of this pathway leads to animals hypersensitive to PFT, but not to other toxic insults. As shown, a strong and specific increase in GFP expression in the intestine can be seen in the presence of the PFT ( Figure 1B , middle panel), consistent with activation of the ire-1-xbp-1 pathway by Cry5B. Consistent with activation of the ire-1-xbp-1 pathway by p38 MAPK in response to PFT but not unfolded proteins, the full induction of both mRNAs by Cry5B, but not tunicamycin, is dependent on sek-1 MAPKK. Specifically, we find that bacterial pore-forming toxins (PFTs) activate the ire-1-xbp-1 branch of the ER Unfolded Protein Response (UPR) in C. abstract: Pore-forming toxins (PFTs) constitute the single largest class of proteinaceous bacterial virulence factors and are made by many of the most important bacterial pathogens. Host responses to these toxins are complex and poorly understood. We find that the endoplasmic reticulum unfolded protein response (UPR) is activated upon exposure to PFTs both in Caenorhabditis elegans and in mammalian cells. Activation of the UPR is protective in vivo against PFTs since animals that lack either the ire-1-xbp-1 or the atf-6 arms of the UPR are more sensitive to PFT than wild-type animals. The UPR acts directly in the cells targeted by the PFT. Loss of the UPR leads to a normal response against unrelated toxins or a pathogenic bacterium, indicating its PFT-protective role is specific. The p38 mitogen-activated protein (MAPK) kinase pathway has been previously shown to be important for cellular defenses against PFTs. We find here that the UPR is one of the key downstream targets of the p38 MAPK pathway in response to PFT since loss of a functional p38 MAPK pathway leads to a failure of PFT to properly activate the ire-1-xbp-1 arm of the UPR. The UPR-mediated activation and response to PFTs is distinct from the canonical UPR-mediated response to unfolded proteins both in terms of its activation and functional sensitivities. These data demonstrate that the UPR, a fundamental intracellular pathway, can operate in intrinsic cellular defenses against bacterial attack. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553261/ doi: 10.1371/journal.ppat.1000176 id: cord-001636-khrx6rnh author: Bordería, Antonio V. title: Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype date: 2015-05-05 words: 7524.0 sentences: 358.0 pages: flesch: 50.0 cache: ./cache/cord-001636-khrx6rnh.txt txt: ./txt/cord-001636-khrx6rnh.txt summary: The total number of minority variants within the P1 structural coding region also significantly increased over the passage series (Fig 1G) , yet there were no significant differences between the numbers observed in Hela and A549 cell passage. The mutations that arise from adaptive passage map to receptor binding sites in a cell-type specific manner Although the HeLa and A549 cell passage series presented similar mean genetic diversity at passage 40 (Fig 1E-1G , P = 0.314), we mined the deep sequence data for all minority variants above 1% frequency that might explain adaptation in each condition (Table 1 ). Given the different frequencies of minority variants observed at passage 40, we examined the patterns of emergence and sequential adaptation to novel environments by deep sequencing every second passage in the A549 cell series (Fig 3 and S1 Dataset). abstract: Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420505/ doi: 10.1371/journal.ppat.1004838 id: cord-312743-9e4yufo5 author: Breiman, Adrien title: Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2 date: 2020-05-21 words: 1388.0 sentences: 66.0 pages: flesch: 45.0 cache: ./cache/cord-312743-9e4yufo5.txt txt: ./txt/cord-312743-9e4yufo5.txt summary: These observations suggested that, when produced in cells that express the A or B blood group enzymes, infectious SARS virions are decorated by the corresponding glycan antigens and that the presence of anti-A and anti-B antibodies in blood group O individuals could prevent infection by blocking virus attachment and entry. We therefore hypothesize that as they are produced in cells coexpressing the ACE2 receptor and either the αGal, NeuGc, or A/B blood group antigens, both SARS-CoV and SARS-CoV2 harbor the corresponding glycan epitopes. Likewise, impairment of transmission by the anti-blood group antibodies may not work to its full potential because of their variable titers in the population and of the high affinity of the SARS-CoV2 for ACE2 [18] , rendering its neutralization more difficult. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32437478/ doi: 10.1371/journal.ppat.1008556 id: cord-321874-eenaixp0 author: Brennan, Greg title: Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range date: 2014-03-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. To establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase R (PKR). Many viral antagonists of these restriction factors are species specific. For example, the rhesus cytomegalovirus PKR antagonist, RhTRS1, inhibits PKR in some African green monkey (AGM) cells, but does not inhibit human or rhesus macaque PKR. To model the evolutionary changes necessary for cross-species transmission, we generated a recombinant vaccinia virus that expresses RhTRS1 in a strain that lacks PKR inhibitors E3L and K3L (VVΔEΔK+RhTRS1). Serially passaging VVΔEΔK+RhTRS1 in minimally-permissive AGM cells increased viral replication 10- to 100-fold. Notably, adaptation in these AGM cells also improved virus replication 1000- to 10,000-fold in human and rhesus cells. Genetic analyses including deep sequencing revealed amplification of the rhtrs1 locus in the adapted viruses. Supplying additional rhtrs1 in trans confirmed that amplification alone was sufficient to improve VVΔEΔK+RhTRS1 replication. Viruses with amplified rhtrs1 completely blocked AGM PKR, but only partially blocked human PKR, consistent with the replication properties of these viruses in AGM and human cells. Finally, in contrast to AGM-adapted viruses, which could be serially propagated in human cells, VVΔEΔK+RhTRS1 yielded no progeny virus after only three passages in human cells. Thus, rhtrs1 amplification in a minimally permissive intermediate host was a necessary step, enabling expansion of the virus range to previously nonpermissive hosts. These data support the hypothesis that amplification of a weak viral antagonist may be a general evolutionary mechanism to permit replication in otherwise resistant host species, providing a molecular foothold that could enable further adaptations necessary for efficient replication in the new host. url: https://www.ncbi.nlm.nih.gov/pubmed/24626510/ doi: 10.1371/journal.ppat.1004002 id: cord-000007-h8upyzb1 author: Butler, Noah S. title: Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant date: 2008-10-24 words: 7690.0 sentences: 354.0 pages: flesch: 47.0 cache: ./cache/cord-000007-h8upyzb1.txt txt: ./txt/cord-000007-h8upyzb1.txt summary: Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Enhancement strategies, which result in augmented responses to the native, subdominant epitope, have been described for both MHC class I and class II-restricted determinants, whereby the most common approaches involve generating a series of conserved and non-conserved mutations at MHC anchor residues, followed by an empiric determination of whether each individual substitution augments T cell effector function [12] . Immunization with the modified peptide resulted in an improved response to the native S598 epitope, demonstrating a true heteroclitic effect and suggesting that this strategy may have clinical applications for reducing viral titer and preventing CTL escape during chronic infections. Seven days following virus infection, brains were harvested from mice and the frequencies of epitope-specific CD8 T cells were determined by ex vivo stimulation and intracellular cytokine staining as described above. abstract: High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2K(b) to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2K(b). The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563037/ doi: 10.1371/journal.ppat.1000186 id: cord-001082-sufwsu77 author: Bär, Séverine title: Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis date: 2013-09-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner. This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection. Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions. By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane. Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles. These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection. It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis. Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g. phosphorylation). While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777860/ doi: 10.1371/journal.ppat.1003605 id: cord-000103-3zh8jmc2 author: Caignard, Grégory title: Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor date: 2009-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736567/ doi: 10.1371/journal.ppat.1000587 id: cord-321957-ybtk9cp1 author: Carey, Brian D. title: Protein Kinase C subtype δ interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylation date: 2020-03-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Protein phosphorylation plays an important role during the life cycle of many viruses. Venezuelan equine encephalitis virus (VEEV) capsid protein has recently been shown to be phosphorylated at four residues. Here those studies are extended to determine the kinase responsible for phosphorylation and the importance of capsid phosphorylation during the viral life cycle. Phosphorylation site prediction software suggests that Protein Kinase C (PKC) is responsible for phosphorylation of VEEV capsid. VEEV capsid co-immunoprecipitated with PKCδ, but not other PKC isoforms and siRNA knockdown of PKCδ caused a decrease in viral replication. Furthermore, knockdown of PKCδ by siRNA decreased capsid phosphorylation. A virus with capsid phosphorylation sites mutated to alanine (VEEV CPD) displayed a lower genomic copy to pfu ratio than the parental virus; suggesting more efficient viral assembly and more infectious particles being released. RNA:capsid binding was significantly increased in the mutant virus, confirming these results. Finally, VEEV CPD is attenuated in a mouse model of infection, with mice showing increased survival and decreased clinical signs as compared to mice infected with the parental virus. Collectively our data support a model in which PKCδ mediated capsid phosphorylation regulates viral RNA binding and assembly, significantly impacting viral pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/32150585/ doi: 10.1371/journal.ppat.1008282 id: cord-262248-q5eijunp author: Casadevall, Arturo title: The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases date: 2015-04-23 words: 2631.0 sentences: 118.0 pages: flesch: 37.0 cache: ./cache/cord-262248-q5eijunp.txt txt: ./txt/cord-262248-q5eijunp.txt summary: Currently, there are no drugs to treat Ebola, but, in the urgency and emergency triggered by the epidemic, two types of Ab-based therapies have been used: convalescent sera from patients who have recovered and a mAb cocktail known as ZMapp produced in plants [3] . For example, given that there is increasing evidence that antibiotic-induced disruptions of the microbiota are associated with deleterious effects in the treatment of bacterial diseases, the high specificity of Ab-based therapies offers a tremendous advantage. Regarding the limitation that highly specific Abs can fail to bind highly related variants, particularly for viruses, there are two strategies to overcome this problem: the development of Abs that target broadly neutralizing epitopes, as has now been demonstrated for HIV [8] , dengue [9] , and influenza viruses [10] , and the generation of Ab cocktails composed of Abs against multiple serotypes or variants, as has been done for rabies virus [11] and Clostridium difficile toxin [12] . abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25905897/ doi: 10.1371/journal.ppat.1004717 id: cord-000025-6zrv687k author: Chachu, Karen A. title: Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection date: 2008-12-12 words: 6996.0 sentences: 340.0 pages: flesch: 48.0 cache: ./cache/cord-000025-6zrv687k.txt txt: ./txt/cord-000025-6zrv687k.txt summary: In the absence of a cell culture system for HuNV, virus like particles (VLPs) that assemble when the viral capsid protein is expressed have been important for evaluating norovirus immune responses [20] [21] [22] [23] . To determine the role of T cells in clearance of acute MNV infection we inoculated WT, MHC Class II-/-, and MHC Class I6b2M-/-mice orally with MNV1.CW3 and measured viral titers in the distal ileum and MLN three, five, seven and 21 days post-infection ( Figure 4B-4E) . Together, these data from primary challenges of non-immune mice lacking antigen presenting molecules or depleted of specific T cell subsets demonstrated that CD4 T cells are important for efficient MNV clearance in the distal ileum especially at days three Lack of any of the three components of the adaptive response: B cells, CD4 T cells, or CD8 T cells significantly diminished vaccine effects generated by either live virus or VP1 capsid protein immunization, and delayed viral clearance during primary infection. abstract: Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587711/ doi: 10.1371/journal.ppat.1000236 id: cord-000409-lpf9lpky author: Chen, Yongwen title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date: 2011-07-07 words: 5540.0 sentences: 296.0 pages: flesch: 49.0 cache: ./cache/cord-000409-lpf9lpky.txt txt: ./txt/cord-000409-lpf9lpky.txt summary: Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. In all, these results demonstrated that PD-1 deficiency led to enhanced pathological damage by MHV-3 in the liver, spleen, lymph node and thymus, where higher levels of PD-1-positive cells were found after infection. Results showed that the expression of FGL2 was principally associated with CD31-positive endothelial cells, CD68-positive macrophages and CD11c-positive DCs. Surprisingly, significantly higher levels of FGL2 were observed after infection in all of PD-1-deficient organs, including the liver, thymus, spleen, lymph nodes, and serum than that in those from WT littermates. However, the number of Foxp3-positive cells in the liver, spleen, lymph node or thymus was not significantly different between PD-1-deficient mice and their WT littermates after 72 h of MHV-3 infection (Fig. S3) . abstract: The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131267/ doi: 10.1371/journal.ppat.1001347 id: cord-297702-vxcj25sn author: Chen, Yuxin title: A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients date: 2020-09-10 words: 5253.0 sentences: 250.0 pages: flesch: 46.0 cache: ./cache/cord-297702-vxcj25sn.txt txt: ./txt/cord-297702-vxcj25sn.txt summary: We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. In this retrospective study, we successively monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the NP protein, RBD protein, S1 protein, and ECD protein in 19 non-severe and 7 severe COVID-19 patients during the disease progression. The severe patients and non-severe patients had comparable reduced fold of IgM, IgG, and IgA binding titer specific to RBD, ECD, S1, and NP protein and neutralization activities. Furthermore, 80.7% of the convalescent sea from COVID-19 patients displayed varying levels of neutralization activities against SARS-CoV-2, which correlated with S1-specific and ECD-specific IgA responses in non-severe patients. abstract: There is an urgent need for effective treatment and preventive vaccine to contain this devastating global pandemic, which requires a comprehensive understanding of humoral responses specific to SARS-CoV-2 during the disease progression and convalescent phase of COVID-19 patients. We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. Most patients generated humoral responses against NP and spike protein-related antigens but with their distinct kinetics profiles. Combined detection of NP and ECD antigens as detecting antigen synergistically improved the sensitivity of the serological assay, compared to that of using NP or RBD as detection antigen. 80.7% of convalescent sera from COVID-19 patients revealed that the varying extents of neutralization activities against SARS-CoV-2. S1-specific and ECD-specific IgA responses were strongly correlated with the neutralization activities in non-severe patients, but not in severe patients. Moreover, the neutralizing activities of the convalescent sera were shown to significantly decline during the period between 21 days to 28 days after hospital discharge, accompanied by a substantial drop in RBD-specific IgA response. Our data provide evidence that are crucial for serological testing, antibody-based intervention, and vaccine design of COVID-19. url: https://doi.org/10.1371/journal.ppat.1008796 doi: 10.1371/journal.ppat.1008796 id: cord-316999-712rit8h author: Chinchio, Eleonora title: Invasive alien species and disease risk: An open challenge in public and animal health date: 2020-10-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/33091094/ doi: 10.1371/journal.ppat.1008922 id: cord-342291-imn7g084 author: Ciminski, Kevin title: Bats reveal the true power of influenza A virus adaptability date: 2020-04-16 words: 2478.0 sentences: 120.0 pages: flesch: 50.0 cache: ./cache/cord-342291-imn7g084.txt txt: ./txt/cord-342291-imn7g084.txt summary: Indeed, the HA of the newly discovered Old World bat H9N2 virus binds to α2,3-sialic In contrast, the internal gene segments of the bat-derived IAVs form two outgroups that are located at a more basal position. Conventional IAVs and the bat H9N2 virus possess the surface glycoprotein neuraminidase (NA), which removes sialic acid residues from infected cells to facilitate the release of newly formed viral particles (Fig 2A) . The amazing ability of H18 to rapidly overcome the absence of a functional N11 suggests that the structure of H18 (and possibly H17) may provide a broader scope of evolutionary flexibility than that of conventional sialic acid-dependent IAVs. It is therefore tempting to speculate that bat IAV HA proteins, and in particular H18, might have the potential to adapt to novel and so far unknown entry receptors different from MHC-II (Fig 2D) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32298389/ doi: 10.1371/journal.ppat.1008384 id: cord-000232-boto4h8x author: Danthi, Pranav title: Bid Regulates the Pathogenesis of Neurotropic Reovirus date: 2010-07-01 words: 9287.0 sentences: 439.0 pages: flesch: 37.0 cache: ./cache/cord-000232-boto4h8x.txt txt: ./txt/cord-000232-boto4h8x.txt summary: Blockade of NF-kB signaling, which diminishes apoptosis induction by reovirus [8, 28] , prevents cleavage of Bid. In comparison to wild-type mice, Bid-deficient mice display diminished susceptibility to reovirus-induced CNS disease following either peroral (PO) or intracranial (IC) inoculation. To directly test whether Bid is required for apoptosis induction following reovirus infection, we compared reovirus-induced apoptosis in wild-type and Bid-deficient MEFs. For these experiments, MEFs were infected with T3D, and apoptosis was assessed by chemiluminescent measurement of the activity of caspase-3 and caspase-7, which serve as effector caspases for both the extrinsic and intrinsic apoptotic pathways ( Figure 2A ). Increase in caspase-3/7 activity following treatment of each cell type with a broad-spectrum protein kinase inhibitor, staurosporine, was equivalent (,5-fold), demonstrating that although Bid-deficient cells possess functional death-signaling pathways, they resist apoptosis induction by reovirus. Analogous to treatment with TNFa, a control NF-kB agonist, reovirus infection resulted in equivalent (,2-to 3-fold) activation of NF-kB-driven gene expression in wild-type and Bid-deficient cells ( Figure 3A ). abstract: Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895667/ doi: 10.1371/journal.ppat.1000980 id: cord-000127-tkxpjlyn author: Dermody, Terence S. title: Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity date: 2009-11-26 words: 2332.0 sentences: 115.0 pages: flesch: 36.0 cache: ./cache/cord-000127-tkxpjlyn.txt txt: ./txt/cord-000127-tkxpjlyn.txt summary: The immunoglobulin superfamily (IgSF) of molecules contains several members that are expressed at the cell surface, bind diverse ligands, and contribute to a variety of cellular activities, including adhesion and immune responses. While structural information about com-plex formation is lacking for the IgSF receptors carcinoembryonic antigen-related cell adhesion molecule, nectin-1, nectin-2, and signaling lymphocyte-activation molecule (SLAM), biochemical studies also implicate their respective D1 domains in virus binding [11] [12] [13] [14] . The evolution of JAM family members prior to the biochemical means to efficiently and extensively diversify antigen receptor genes, along with the structural similarities in the binding surfaces of virus receptors and immunoglobulins, provides strong support for the contention that viruses and perhaps other pathogens that engage IgSF receptors contributed to the selection of humoral mediators of adaptive immunity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777377/ doi: 10.1371/journal.ppat.1000481 id: cord-325192-italbsed author: Desai, Tanay M. title: IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion date: 2014-04-03 words: 8249.0 sentences: 437.0 pages: flesch: 51.0 cache: ./cache/cord-325192-italbsed.txt txt: ./txt/cord-325192-italbsed.txt summary: Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. Our results show that IFITM3 does not inhibit the lipid mixing stage of IAV fusion but blocks the release of viral contents into the cytosol, and that this phenotype does not correlate with cholesterol accumulation in intracellular compartments. Our results thus demonstrate that IFITM3 restricts the IAV fusion at a post-hemifusion step, most likely at the point of fusion pore opening, as evidenced by the dramatic decrease of the BlaM signal in A549 and MDCK cells expressing this protein (Fig. 1A ). Neither IAV lipid mixing (vDiD dequenching) nor fusion (BlaM signal) was inhibited by silencing NPC1 in A549 cells (Fig. 5E, F) . abstract: Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes. url: https://www.ncbi.nlm.nih.gov/pubmed/24699674/ doi: 10.1371/journal.ppat.1004048 id: cord-263239-andje0wu author: Dorobantu, Cristina M. title: Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus date: 2015-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cardioviruses, including encephalomyocarditis virus (EMCV) and the human Saffold virus, are small non-enveloped viruses belonging to the Picornaviridae, a large family of positive-sense RNA [(+)RNA] viruses. All (+)RNA viruses remodel intracellular membranes into unique structures for viral genome replication. Accumulating evidence suggests that picornaviruses from different genera use different strategies to generate viral replication organelles (ROs). For instance, enteroviruses (e.g. poliovirus, coxsackievirus, rhinovirus) rely on the Golgi-localized phosphatidylinositol 4-kinase III beta (PI4KB), while cardioviruses replicate independently of the kinase. By which mechanisms cardioviruses develop their ROs is currently unknown. Here we show that cardioviruses manipulate another PI4K, namely the ER-localized phosphatidylinositol 4-kinase III alpha (PI4KA), to generate PI4P-enriched ROs. By siRNA-mediated knockdown and pharmacological inhibition, we demonstrate that PI4KA is an essential host factor for EMCV genome replication. We reveal that the EMCV nonstructural protein 3A interacts with and is responsible for PI4KA recruitment to viral ROs. The ensuing phosphatidylinositol 4-phosphate (PI4P) proved important for the recruitment of oxysterol-binding protein (OSBP), which delivers cholesterol to EMCV ROs in a PI4P-dependent manner. PI4P lipids and cholesterol are shown to be required for the global organization of the ROs and for viral genome replication. Consistently, inhibition of OSBP expression or function efficiently blocked EMCV RNA replication. In conclusion, we describe for the first time a cellular pathway involved in the biogenesis of cardiovirus ROs. Remarkably, the same pathway was reported to promote formation of the replication sites of hepatitis C virus, a member of the Flaviviridae family, but not other picornaviruses or flaviviruses. Thus, our results highlight the convergent recruitment by distantly related (+)RNA viruses of a host lipid-modifying pathway underlying formation of viral replication sites. url: https://doi.org/10.1371/journal.ppat.1005185 doi: 10.1371/journal.ppat.1005185 id: cord-265947-7j9qqi8w author: Du, Wenjuan title: The 2(nd) sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance date: 2019-06-10 words: 9564.0 sentences: 464.0 pages: flesch: 50.0 cache: ./cache/cord-265947-7j9qqi8w.txt txt: ./txt/cord-265947-7j9qqi8w.txt summary: NAs of avian, but not human viruses, contain a functional 2(nd) sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. Using a recently established BLI-based kinetic binding assay [37] an enhanced initial binding rate to 3''SLNLN but not 6''SLNLN ( Fig 4A and 4B ), was observed for hH3aN2 virus containing Role for 2 nd SIA-binding site of IAV NA in HA-NA-receptor balance a functional 2SBS in comparison to hH3hN2. We therefore studied the effect of the 2SBS in NA when combined with an avian-type Role for 2 nd SIA-binding site of IAV NA in HA-NA-receptor balance HA preferring binding to α2,3-linked SIAs. We generated the corresponding recombinant A/ Hong Kong/1/68 (H3N2) viruses containing 7 amino acid substitutions in the HA (see S8A Fig) . abstract: Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2(nd) sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein. url: https://www.ncbi.nlm.nih.gov/pubmed/31181126/ doi: 10.1371/journal.ppat.1007860 id: cord-011380-kfkp1zpn author: Duru, Adil Doganay title: Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination date: 2020-05-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral escape from CD8(+) cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8(+) T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224568/ doi: 10.1371/journal.ppat.1008244 id: cord-309056-ul9q3ebx author: Dutch, Rebecca Ellis title: Entry and Fusion of Emerging Paramyxoviruses date: 2010-06-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/20585631/ doi: 10.1371/journal.ppat.1000881 id: cord-003441-810r5q03 author: Dzimianski, John V. title: Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity date: 2019-01-10 words: 10973.0 sentences: 578.0 pages: flesch: 54.0 cache: ./cache/cord-003441-810r5q03.txt txt: ./txt/cord-003441-810r5q03.txt summary: Specifically, that CCHFV vOTU DUB activity is not as promiscuous towards ubiquitinated host proteins as it first seemed based on the overexpression studies, but appears to be restricted to a targeted subset of cellular substrates associated with suppression of RIG-I-mediated early cellular responses to infection. Additionally, a structure of the FARV vOTU provides details into the structural nature of the additional residues in Hughes orthonairovirus vOTUs. Structureinformed mutagenesis of FARV vOTU identified residues involved specifically in di-Ub binding, representing the first report of the role of a second site involved in di-Ub binding in nairovirus vOTUs. This novel enzymatic and structural data not only provides insight into the nature of vOTU diversity, but also lays a foundation for understanding the impact of the vOTU interaction with the innate immune response and its connection to viral pathogenesis. Intriguingly, the vOTUs showed a diverse range of activity towards Ub. In general, vOTUs can be divided into groups possessing high (CCHFV, HAZV, NSDV/GANV, TAGV), moderate (DUGV, KUPEV, FARV, QYBV, ISKV), or low activity (ERVEV, DGKV, LPHV, HpTV-1) (Fig 2A) . abstract: Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343935/ doi: 10.1371/journal.ppat.1007515 id: cord-315316-w7cn9iqp author: Earnest, James T. title: The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases date: 2017-07-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence. url: https://www.ncbi.nlm.nih.gov/pubmed/28759649/ doi: 10.1371/journal.ppat.1006546 id: cord-002125-anp238gu author: Effantin, Grégory title: Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture date: 2016-07-11 words: 8022.0 sentences: 401.0 pages: flesch: 55.0 cache: ./cache/cord-002125-anp238gu.txt txt: ./txt/cord-002125-anp238gu.txt summary: Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP). In order to obtain structural insight into PFV organization at medium resolution we used cryo-electron tomography (cryo-ET) and microscopy (cryo-EM) to analyze isolated wild-type particles and variants with mutations in PFV Gag and Env proteins. To gain more insights into the structure of the PFV glycoprotein, we use 3D reconstructions of iNAB and iFuse Env hexagonal assemblies of six trimers determined by subtomogram averaging as initial references for automatic particle selection of micrographs acquired by cryo-EM (S4 Fig) (see Material and Methods). abstract: Foamy viruses (FV) belong to the genus Spumavirus, which forms a distinct lineage in the Retroviridae family. Although the infection in natural hosts and zoonotic transmission to humans is asymptomatic, FVs can replicate well in human cells making it an attractive gene therapy vector candidate. Here we present cryo-electron microscopy and (cryo-)electron tomography ultrastructural data on purified prototype FV (PFV) and PFV infected cells. Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP). The viral membrane contains trimeric Env glycoproteins partly arranged in interlocked hexagonal assemblies. In situ 3D reconstruction by subtomogram averaging of wild type Env and of a Env gp48(TM)- gp80(SU) cleavage site mutant showed a similar spike architecture as well as stabilization of the hexagonal lattice by clear connections between lower densities of neighboring trimers. Cryo-EM was employed to obtain a 9 Å resolution map of the glycoprotein in its pre-fusion state, which revealed extensive trimer interactions by the receptor binding subunit gp80(SU) at the top of the spike and three central helices derived from the fusion protein subunit gp48(TM). The lower part of Env, presumably composed of interlaced parts of gp48(TM), gp80(SU) and gp18(LP) anchors the spike at the membrane. We propose that the gp48(TM) density continues into three central transmembrane helices, which interact with three outer transmembrane helices derived from gp18(LP). Our ultrastructural data and 9 Å resolution glycoprotein structure provide important new insights into the molecular architecture of PFV and its distinct evolutionary relationship with other members of the Retroviridae. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939959/ doi: 10.1371/journal.ppat.1005721 id: cord-338400-30vl2hks author: Epstein, Jonathan H. title: Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh date: 2010-07-01 words: 4653.0 sentences: 246.0 pages: flesch: 50.0 cache: ./cache/cord-338400-30vl2hks.txt txt: ./txt/cord-338400-30vl2hks.txt summary: Phylogenetic analysis indicates that this first GBV-like flavivirus reported in bats constitutes a distinct species within the Flaviviridae family and is ancestral to the GBV-A and -C virus clades. GBV-A viruses have been described in New World primates and are not known to infect humans [17] [18] [19] , while GBV-C (also known as Hepatitis G virus (HGV)) have frequently been isolated from humans in many regions of the World, including India and Bangladesh [19] [20] [21] [22] [23] , and from wild chimpanzees (Pan troglodytes) in Africa [24, 25] . Our findings provide new insight into the range of known hosts for GB-like viruses and demonstrate the power of unbiased sequencing to characterize the diversity of potentially zoonotic pathogens carried by bats and other reservoirs. Molecular analyses of sera from Pteropus giganteus bats from Faridpur, Bangladesh led to the identification of a 9,633 nt sequence consistent in genomic organization with known GBV and other species within the family Flaviviridae [16] . abstract: Bats are reservoirs for a wide range of zoonotic agents including lyssa-, henipah-, SARS-like corona-, Marburg-, Ebola-, and astroviruses. In an effort to survey for the presence of other infectious agents, known and unknown, we screened sera from 16 Pteropus giganteus bats from Faridpur, Bangladesh, using high-throughput pyrosequencing. Sequence analyses indicated the presence of a previously undescribed virus that has approximately 50% identity at the amino acid level to GB virus A and C (GBV-A and -C). Viral nucleic acid was present in 5 of 98 sera (5%) from a single colony of free-ranging bats. Infection was not associated with evidence of hepatitis or hepatic dysfunction. Phylogenetic analysis indicates that this first GBV-like flavivirus reported in bats constitutes a distinct species within the Flaviviridae family and is ancestral to the GBV-A and -C virus clades. url: https://doi.org/10.1371/journal.ppat.1000972 doi: 10.1371/journal.ppat.1000972 id: cord-302340-pw2xqhwa author: Feeley, Eric M. title: IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry date: 2011-10-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats. url: https://www.ncbi.nlm.nih.gov/pubmed/22046135/ doi: 10.1371/journal.ppat.1002337 id: cord-000660-tsvzg0ax author: Fensterl, Volker title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis date: 2012-05-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355090/ doi: 10.1371/journal.ppat.1002712 id: cord-338053-8zlxsf1z author: Foo, Suan-Sin title: Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation date: 2015-02-19 words: 9156.0 sentences: 502.0 pages: flesch: 51.0 cache: ./cache/cord-338053-8zlxsf1z.txt txt: ./txt/cord-338053-8zlxsf1z.txt summary: In summary, our data demonstrated the crucial role of PTX3 in modulating alphavirus-induced immune responses and disease manifestation through its N-terminal interaction with the virus particles leading to enhanced viral entry and replication. To confirm that the results of enhanced virus production was due to PTX3 enhancing RRV replication, HEK 293T cells transiently transfected with vector or hPTX3 plasmids were harvested at 20 hour post transfection (hpt) ( To further characterize the effect of PTX3 during alphaviral infection, we examined the potential of PTX3 to directly interact with the virus and enhance viral entry. To demonstrate that the effect of PTX3on enhancing RRV entry and replication contributed to the increased level of virus detected in the in vivo studies, we performed RRV infection on primary fibroblasts isolated from tails of PTX3 -/and WT C57BL/6 mice. abstract: The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/25695775/ doi: 10.1371/journal.ppat.1004649 id: cord-001700-c6elsnag author: Fusco, Marnie L. title: Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs date: 2015-06-26 words: 6459.0 sentences: 329.0 pages: flesch: 57.0 cache: ./cache/cord-001700-c6elsnag.txt txt: ./txt/cord-001700-c6elsnag.txt summary: Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. To generate MARV GP-specific mAbs, BALB/c mice were immunized with GPΔmuc antigens from either MARV strain Ci67, Musoke, Angola, or Ravn ( Fig 1A) . To characterize the binding of mAbs, we performed enzyme-linked immunosorbent assays (ELISAs) with recombinant GPs from four MARV strains, and determined EC50 values for binding with different forms of MARV Ravn GP: GP, GPΔmuc, GPcl (Fig 2A) . Two of the highly cross-reactive MARV antibodies, mAbs 40G1 and 2D8, also exhibit binding to Ebola, Sudan, Bundibugyo and Reston virus mucin-deleted GPs by ELISA (Fig 5A) . abstract: The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482612/ doi: 10.1371/journal.ppat.1005016 id: cord-275307-d7htyfcl author: Gaglia, Marta Maria title: Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX date: 2015-12-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Many viruses express factors that reduce host gene expression through widespread degradation of cellular mRNA. An example of this class of proteins is the mRNA-targeting endoribonuclease SOX from the gamma-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). Previous studies indicated that cleavage of messenger RNAs (mRNA) by SOX occurs at specific locations defined by the sequence of the target RNA, which is at odds with the down-regulation of a large portion of cellular transcripts. In this study, we address this paradox by using high-throughput sequencing of cleavage intermediates combined with a custom bioinformatics-based analysis pipeline to identify SOX cleavage sites across the mRNA transcriptome. These data, coupled with targeted mutagenesis, reveal that while cleavage sites are specific and reproducible, they are defined by a degenerate sequence motif containing a small number of conserved residues rather than a strong consensus sequence. This degenerate element is well represented in both human and KSHV mRNA, and its presence correlates with RNA destabilization by SOX. This represents a new endonuclease targeting strategy, in which use of a degenerate targeting element enables RNA cleavage at specific locations without restricting the range of targets. Furthermore, it shows that strong target selectivity can be achieved without a high degree of sequence specificity. url: https://www.ncbi.nlm.nih.gov/pubmed/26646420/ doi: 10.1371/journal.ppat.1005305 id: cord-260949-w2xuf15h author: Galluzzi, Lorenzo title: Viral Control of Mitochondrial Apoptosis date: 2008-05-30 words: 10923.0 sentences: 533.0 pages: flesch: 37.0 cache: ./cache/cord-260949-w2xuf15h.txt txt: ./txt/cord-260949-w2xuf15h.txt summary: Bcl-2/Bcl-X L stabilizes mitochondrial membranes via multiple mechanisms, including (1) the sequestration into inactive complexes of its proapoptotic counterparts, Bax, Bak, and BH3only proteins (e.g., Bid) (for review: [S65,S78]), (2) inhibitory interactions with PTPC constituents, in particular with VDAC and the adenine nucleotide translocase (ANT) [12, 14] , (3) an enhancement of Cyt c oxidase activity and mitochondrial respiration [S79], and/or (4) indirect effects on intracellular Ca 2+ stores of the ER [S80,S81]. With regard to this, viral factors can be classified into one of the four following subgroups: proapoptotic proteins (1) that insert into mitochondrial membranes and hence trigger MMP through the action of amphipathic a-helical domains or (2) that promote MMP indirectly, through the activition of host-encoded factors (Table 1) , and antiapoptotic modulators (3) that exhibit sequence and/or structural similarity to multidomain BH1-4 members of the Bcl-2 family (so-called viral Bcl-2 proteins [vBcl-2s]) or (4) that inhibit apoptosis via other mechanisms (Table 2) . abstract: Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus. url: https://doi.org/10.1371/journal.ppat.1000018 doi: 10.1371/journal.ppat.1000018 id: cord-353703-u86ggw11 author: Gao, Peng title: Reprogramming the unfolded protein response for replication by porcine reproductive and respiratory syndrome virus date: 2019-11-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The unfolded protein response (UPR) in the endoplasmic reticulum (ER) constitutes a critical component of host innate immunity against microbial infections. In this report, we show that porcine reproductive and respiratory syndrome virus (PRRSV) utilizes the UPR machinery for its own benefit. We provide evidence that the virus targets the UPR central regulator GRP78 for proteasomal degradation via a mechanism that requires viral glycoprotein GP2a, while both IRE1-XBP1s and PERK-eIF2α-ATF4 signaling branches of the UPR are turned on at early stage of infection. The activated effector XBP1s was found to enter the nucleus, but ATF4 was unexpectedly diverted to cytoplasmic viral replication complexes by means of nonstructural proteins nsp2/3 to promote viral RNA synthesis. RNAi knockdown of either ATF4 or XBP1s dramatically attenuated virus titers, while overexpression caused increases. These observations reveal attractive host targets (e.g., ATF4 and XBP1s) for antiviral drugs and have implications in vaccine development. url: https://www.ncbi.nlm.nih.gov/pubmed/31738790/ doi: 10.1371/journal.ppat.1008169 id: cord-281404-5a8au32c author: Gastaldello, Stefano title: Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date: 2013-10-10 words: 7139.0 sentences: 337.0 pages: flesch: 42.0 cache: ./cache/cord-281404-5a8au32c.txt txt: ./txt/cord-281404-5a8au32c.txt summary: The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Here we report that induction of the productive virus cycle has no appreciable effects on the global levels of protein ubiquitination but is accompanied by a BPLF1-dependent decrease of cullin neddylation and stabilization of nuclear CRL substrates. The Akata-Bx1 cell line was used to study the contribution of the Ub-and NEDD8-specific deconjugase activities of the EBV large tegument protein BPLF1 to the productive virus cycle. In order to assess whether this regulatory interaction may operate during virus replication, the productive cycle was induced in Akata-Bx1 cells transiently transfected with plasmids expressing Myc-tagged CAND1 or the CAND1 Nterminus that compete for BPLF1 binding to cullins, or, as controls, the CAND1 C-terminus that binds to the opposite end of the cullin scaffold, and the empty vector ( Figure 5A ). abstract: The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication. url: https://doi.org/10.1371/journal.ppat.1003664 doi: 10.1371/journal.ppat.1003664 id: cord-304747-ojyxs3cp author: Gaynor, Anne M title: Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections date: 2007-05-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen. url: https://www.ncbi.nlm.nih.gov/pubmed/17480120/ doi: 10.1371/journal.ppat.0030064 id: cord-287219-qxkwjkif author: Geisbert, Thomas W. title: Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates date: 2008-11-28 words: 5413.0 sentences: 247.0 pages: flesch: 44.0 cache: ./cache/cord-287219-qxkwjkif.txt txt: ./txt/cord-287219-qxkwjkif.txt summary: In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). Therefore, we conducted a study to assess the pathogenicity and protective efficacy of the recombinant VSVbased ZEBOV vaccine vector in rhesus macaques that were infected with simian-human immunodeficiency virus (SHIV) which is known to deplete the populations of naive CD4+ T cells, naive CD8+ T cells, and memory CD4+ T cells in these animals [22, 23] . Disease progressed in two of the VSVDG/ZEBOVGP-vaccinated SHIV-infected monkeys (Subject #5 and 6) and both of the placebo control animals with the development of additional evidence of clinical illness including increased levels of serum enzymes associated with liver function, depression, anorexia, and the appearance of macular rashes (Table 3 ). abstract: Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV. url: https://doi.org/10.1371/journal.ppat.1000225 doi: 10.1371/journal.ppat.1000225 id: cord-002423-1u44tdrj author: Geoghegan, Jemma L. title: Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families date: 2017-02-08 words: 6186.0 sentences: 267.0 pages: flesch: 44.0 cache: ./cache/cord-002423-1u44tdrj.txt txt: ./txt/cord-002423-1u44tdrj.txt summary: While this method does not explicitly model host-switching events, it does provide a simple means to compare multiple topologies of virus-host pairs, and accounts for differences in sample size and the fact that several viruses from a specific family can infect a single host species. Across the data set as a whole we found that all virus families displayed relatively large tree topological distances with nPH85 values of !0.6, suggesting that cross-species transmission is widespread, at least at the family-level (Fig 2; S3 Table) . As with the analysis of topological distances, this revealed that cross-species transmission was the most common evolutionary event in all virus families studied here, with co-divergence consistently less frequent (with the possible exception of the Hepadnaviridae-see below), and lineage duplication and extinction playing a much more minor role. To investigate the comparative prevalence of cross-species transmission among viruses we measured the congruence between virus and host phylogenetic trees using a normalized tree topological distance-based approach (nPH85, [14] ). abstract: The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319820/ doi: 10.1371/journal.ppat.1006215 id: cord-325825-0lyt8gfq author: Griffiths, Samantha J. title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 words: 12504.0 sentences: 601.0 pages: flesch: 45.0 cache: ./cache/cord-325825-0lyt8gfq.txt txt: ./txt/cord-325825-0lyt8gfq.txt summary: Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). abstract: Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome. url: https://doi.org/10.1371/journal.ppat.1003514 doi: 10.1371/journal.ppat.1003514 id: cord-304815-3datxv8j author: Gronvall, Gigi Kwik title: The Scientific Response to a Pandemic date: 2006-02-24 words: 1522.0 sentences: 92.0 pages: flesch: 49.0 cache: ./cache/cord-304815-3datxv8j.txt txt: ./txt/cord-304815-3datxv8j.txt summary: More than 150 scientists and public health practitioners from 25 countries gathered in Lyon, France, to hear speakers from the WHO, the European Commission, scientific journals, Interpol, and public health networks-many of the institutions and individuals who will likely play key roles in the global response to the next pandemic. By discussing the biosafety and biosecurity challenges presented by past epidemics such as SARS, participants recognized the importance of scientific and public health collaboration in combating disease-and the need to plan. Researchers will need to share biological samples between laboratories, sometimes internationally; decision makers and journalists will want the latest information, which may not be peer reviewed; and researchers will risk contracting the disease they research, which could then spread outside of the laboratory. Scientists need access to samples from patients and laboratories in order to conduct research and public health surveillance, as well as to develop diagnostic tests. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/16738708/ doi: 10.1371/journal.ppat.0020009 id: cord-002706-m3y35ozx author: Guo, Fang title: HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways date: 2017-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or “empty” capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629035/ doi: 10.1371/journal.ppat.1006658 id: cord-003169-bdw5ke4i author: Guo, Hongbo title: Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces date: 2018-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors determine viral fitness and host tropism. Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor-repertoire. The crucial but poorly understood dynamics of these multivalent virus-receptor interactions cannot be properly analyzed using equilibrium binding models and endpoint binding assays. In this study, the use of biolayer interferometric analysis revealed the virtually irreversible nature of IAV binding to surfaces coated with synthetic sialosides or engineered sialoglycoproteins in the absence of NA activity. In addition to HA, NA was shown to be able to contribute to the initial binding rate while catalytically active. Virus-receptor binding in turn contributed to receptor cleavage by NA. Multiple low-affinity HA-SIA interactions resulted in overall extremely high avidity but also permitted a dynamic binding mode, in which NA activity was driving rolling of virus particles over the receptor-surface. Virus dissociation only took place after receptor density of the complete receptor-surface was sufficiently decreased due to NA activity of rolling IAV particles. The results indicate that in vivo IAV particles, after landing on the mucus layer, reside continuously in a receptor-bound state while rolling through the mucus layer and over epithelial cell surfaces driven by the HA-NA-receptor balance. Quantitative BLI analysis enabled functional examination of this balance which governs this dynamic and motile interaction that is expected to be crucial for penetration of the mucus layer and subsequent infection of cells by IAV but likely also by other enveloped viruses carrying a receptor-destroying enzyme in addition to a receptor-binding protein. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107293/ doi: 10.1371/journal.ppat.1007233 id: cord-013481-3zwq67do author: Guo, Kejun title: Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis date: 2020-10-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the ‘interferome’. Quantitative differences in IFNAR binding correlate with antiviral activity, but whether IFN-Is exhibit qualitative differences remains controversial. Moreover, the IFN-I response is protective during acute HIV-1 infection, but likely pathogenic during the chronic stages. To gain a deeper understanding of the IFN-I response, we compared the interferomes of IFNα subtypes dominantly-expressed in HIV-1-exposed plasmacytoid dendritic cells (1, 2, 5, 8 and 14) and IFNβ in the earliest cellular targets of HIV-1 infection. Primary gut CD4 T cells from 3 donors were treated for 18 hours ex vivo with individual IFN-Is normalized for IFNAR signaling strength. Of 1,969 IFN-regulated genes, 246 ‘core ISGs’ were induced by all IFN-Is tested. However, many IFN-regulated genes were not shared between the IFNα subtypes despite similar induction of canonical antiviral ISGs such as ISG15, RSAD2 and MX1, formally demonstrating qualitative differences between the IFNα subtypes. Notably, IFNβ induced a broader interferome than the individual IFNα subtypes. Since IFNβ, and not IFNα, is upregulated during chronic HIV-1 infection in the gut, we compared core ISGs and IFNβ-specific ISGs from colon pinch biopsies of HIV-1-uninfected (n = 13) versus age- and gender-matched, antiretroviral-therapy naïve persons with HIV-1 (PWH; n = 19). Core ISGs linked to inflammation, T cell activation and immune exhaustion were elevated in PWH, positively correlated with plasma lipopolysaccharide (LPS) levels and gut IFNβ levels, and negatively correlated with gut CD4 T cell frequencies. In sharp contrast, IFNβ-specific ISGs linked to protein translation and anti-inflammatory responses were significantly downregulated in PWH, negatively correlated with gut IFNβ and LPS, and positively correlated with plasma IL6 and gut CD4 T cell frequencies. Our findings reveal qualitative differences in interferome induction by diverse IFN-Is and suggest potential mechanisms for how IFNβ may drive HIV-1 pathogenesis in the gut. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592919/ doi: 10.1371/journal.ppat.1008986 id: cord-001769-2sdg5ll7 author: Guo, Sheng title: The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis date: 2015-09-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1 (-/-)) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45(+)Gr-1(high) neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47 (phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569300/ doi: 10.1371/journal.ppat.1005155 id: cord-271692-60nlid3c author: Guo, Wen-Ping title: Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores, and Rodents date: 2013-02-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses. url: https://doi.org/10.1371/journal.ppat.1003159 doi: 10.1371/journal.ppat.1003159 id: cord-288231-vg8bwed9 author: Haagmans, Bart L. title: The Application of Genomics to Emerging Zoonotic Viral Diseases date: 2009-10-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly invaded species. The ultimate challenge is to link pathogen and host genomics data with biological outcomes of zoonotic transmission and to translate the integrated data into novel intervention strategies that eventually will allow the effective control of newly emerging infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/19855817/ doi: 10.1371/journal.ppat.1000557 id: cord-289879-fh7ic0kp author: Hatesuer, Bastian title: Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice date: 2013-12-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses. url: https://doi.org/10.1371/journal.ppat.1003774 doi: 10.1371/journal.ppat.1003774 id: cord-286137-4cbh3u3z author: Honce, Rebekah title: They are what you eat: Shaping of viral populations through nutrition and consequences for virulence date: 2020-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32790755/ doi: 10.1371/journal.ppat.1008711 id: cord-355610-7xy4s483 author: Hu, Dan title: A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III date: 2019-06-26 words: 6168.0 sentences: 307.0 pages: flesch: 52.0 cache: ./cache/cord-355610-7xy4s483.txt txt: ./txt/cord-355610-7xy4s483.txt summary: Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate. Its fully human origin, the germline-like nature, combined with high-affinity and broad neutralizing activity toward all DENV serotypes, suggest that m366.6 is a promising candidate antiviral agent and may also provide a unique template for designing effective dengue vaccine immunogens. Two antibodies, designated as m360 and m366, bound potently to DENV DIIIs. Their scFv gene were fused with human IgG1 Fc for protein expression, and surface plasmon resonance (SPR) experiments were used to evaluate the antigens binding. abstract: Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate. url: https://www.ncbi.nlm.nih.gov/pubmed/31242272/ doi: 10.1371/journal.ppat.1007836 id: cord-342419-liaihahj author: Huang, Jiachen title: Antibody recognition of the Pneumovirus fusion protein trimer interface date: 2020-10-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human metapneumovirus (hMPV) is a leading cause of viral respiratory infection in children, and can cause severe lower respiratory tract infection in infants, the elderly, and immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological properties of hMPV F remain poorly understood. To further define the humoral immune response to the hMPV F protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 and MPV465. Both mAbs are neutralizing in vitro and were determined to target a unique antigenic site using competitive biolayer interferometry. We determined both MPV458 and MPV465 have higher affinity for monomeric hMPV F than trimeric hMPV F. MPV458 was co-crystallized with hMPV F, and the mAb primarily interacts with an alpha helix on the F2 region of the hMPV F protein. Surprisingly, the major epitope for MPV458 lies within the trimeric interface of the hMPV F protein, suggesting significant breathing of the hMPV F protein must occur for host immune recognition of the novel epitope. In addition, significant glycan interactions were observed with a somatically mutated light chain framework residue. The data presented identifies a novel epitope on the hMPV F protein for epitope-based vaccine design, and illustrates a new mechanism for human antibody neutralization of viral glycoproteins. url: https://www.ncbi.nlm.nih.gov/pubmed/33035266/ doi: 10.1371/journal.ppat.1008942 id: cord-332205-ydijp66b author: Hufsky, Franziska title: Virologists—Heroes need weapons date: 2018-02-08 words: 1165.0 sentences: 69.0 pages: flesch: 53.0 cache: ./cache/cord-332205-ydijp66b.txt txt: ./txt/cord-332205-ydijp66b.txt summary: Nowadays, nearly everyone in the life sciences has used BLAST [8] at least once, or made an alignment, or asked a bioinformatician to analyze high-throughput sequencing data. Bioinformaticians routinely have to develop tailored, study-specific algorithms and tools used by a wide variety of scientists, including biochemists, biologists, geneticists, and molecular life scientists; but we rarely find virus-specific tools used by virologists. But astonishingly, we now know that the human genome consists of 8%-60% virus-derived sequences (depending on how this is measured: 8% can be directly traced back to viruses, whereas a figure of 60% includes LINEs and SINEs that are thought to be of viral origin [12] ). The EVBC aims to develop bioinformatical tools for nearly all areas: (1) for detection of viruses, e.g., from high-throughput sequencing data; (2) virus assembly; (3) quasispecies reconstruction; (4) intraviral interactions; (5) virus entry, i.e., protein-protein interaction; (6) virus -host interactions; (7) phylogeny/cophylogeny; and (8) therapy. abstract: nan url: https://doi.org/10.1371/journal.ppat.1006771 doi: 10.1371/journal.ppat.1006771 id: cord-325624-6anybxnk author: Ireland, Derek D. C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 words: 8082.0 sentences: 397.0 pages: flesch: 43.0 cache: ./cache/cord-325624-6anybxnk.txt txt: ./txt/cord-325624-6anybxnk.txt summary: The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. abstract: IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(−/−)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination. url: https://www.ncbi.nlm.nih.gov/pubmed/19798426/ doi: 10.1371/journal.ppat.1000602 id: cord-333473-c1lykari author: Irigoyen, Nerea title: High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling date: 2016-02-26 words: 18258.0 sentences: 844.0 pages: flesch: 56.0 cache: ./cache/cord-333473-c1lykari.txt txt: ./txt/cord-333473-c1lykari.txt summary: Also, it has been employed in the study of the replication of large DNA viruses; namely, human cytomegalovirus [17] [18] , Kaposi''s sarcoma-associated herpesvirus [19] , herpes simplex virus 1 [20] , vaccinia virus [21] , and bacteriophage lambda [22] , providing insights into the temporal regulation of gene expression in these viruses and identifying numerous previously unrecognized translated ORFs, including novel protein-coding ORFs and short regulatory uORFs. In this paper, we describe the first analysis of RNA virus replication and gene expression by ribosome profiling (and parallel RNASeq), using MHV as a model system. The latter are calculated on a per gene (rather than per transcript) basis, using RNASeq and RiboSeq reads contained entirely within annotated CDS regions (i.e. excluding 5 0 and 3 0 UTRs and also RPFs accumulating at or near to initiation or termination sites), and, like the virus values, are expressed relative to the mean levels for the cell (due to normalization by library size). abstract: Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global “snap-shot” of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus. url: https://www.ncbi.nlm.nih.gov/pubmed/26919232/ doi: 10.1371/journal.ppat.1005473 id: cord-002542-f7l4ty2j author: Jaworski, Elizabeth title: Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus date: 2017-05-05 words: 11789.0 sentences: 535.0 pages: flesch: 49.0 cache: ./cache/cord-002542-f7l4ty2j.txt txt: ./txt/cord-002542-f7l4ty2j.txt summary: Using a combination of longand short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. By combining these data, we aimed to determine the correlation of recombination events within single RNA virus genomes, characterize the distribution of defective RNA genomes, and determine the exact make-up of DI-RNAs during serial passaging of FHV in cell culture. This observation indicates the protection of cells from infection and/or CPE when supplied with a large dose of viral particles that contain a large proportion of DI-RNAs. In this manuscript, we sought to provide a thorough and comprehensive analysis of the frequency and identity of recombination events present during the serial passaging of Flock House virus in cell culture in order to elucidate the pathways and mechanism of DI-RNA emergence and evolution. abstract: Defective-Interfering RNAs (DI-RNAs) have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed ‘ClickSeq’ due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies’s (ONT) MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these ‘intermediate’ species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer ‘mature’ DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have important consequences for our understanding of the mechanisms, determinants and limitations in the emergence and evolution of DI-RNAs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435362/ doi: 10.1371/journal.ppat.1006365 id: cord-253783-3a1qde41 author: Johnson, Christopher J title: Prions Adhere to Soil Minerals and Remain Infectious date: 2006-04-14 words: 5461.0 sentences: 283.0 pages: flesch: 51.0 cache: ./cache/cord-253783-3a1qde41.txt txt: ./txt/cord-253783-3a1qde41.txt summary: We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. X-ray diffraction analysis provided no evidence that PrP Sc entered Mte interlayer spaces (Mte d 001 spacings were 1.22 nm and 1.47 nm before and after PrP Sc adsorption, respectively); prion protein appeared to adsorb to only external clay surfaces. Prion protein desorbed from Kte and quartz did not exhibit a change in molecular mass ( Figure 1A ), suggesting that surface properties specific to Mte were responsible for the cleavage. To control for any unbound prion protein that may have cosedimented with Mte particles, mineral-free PrP Sc suspensions were processed in the same manner as in sorption experiments. Our results demonstrate that all soil mineral surfaces examined bound PrP Sc and that Mte and quartz have larger specific binding capacities for PrP Sc than does Kte (Figure 1 ). abstract: An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities of each mineral. Furthermore, we observed that PrP(Sc) desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc) and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious. Results from our study suggest that PrP(Sc) released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent. url: https://www.ncbi.nlm.nih.gov/pubmed/16617377/ doi: 10.1371/journal.ppat.0020032 id: cord-351548-jvl63652 author: Juranic Lisnic, Vanda title: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date: 2013-09-26 words: 11978.0 sentences: 623.0 pages: flesch: 49.0 cache: ./cache/cord-351548-jvl63652.txt txt: ./txt/cord-351548-jvl63652.txt summary: Finally, a recent transcriptomic analysis of newly synthesized RNA in MCMV infected fibroblasts [15] applied RNA-Seq technology to study regulation of viral gene expression and identified a very early peak of viral gene transcriptional activity at 1-2 hours post infection followed by rapid cellular countermeasures but did not attempt to re-annotate MCMV genome. The MCMV transcripts identified through our classical cDNA cloning and sequencing (green arrows) and the RNA-Seq expression profiles (gray histograms), showed complementary results to each other but diverged dramatically from current annotations. Because cDNA cloning and RNA-Seq identified significant differences between the MCMV transcriptome and current annotations, we performed an in depth analysis of several genomic regions by northern analyses ( Figure 5 , Figures S2, S3 , S4, S5) using our cDNA clones to generate strand specific riboprobes ( Table 1) . abstract: Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. url: https://doi.org/10.1371/journal.ppat.1003611 doi: 10.1371/journal.ppat.1003611 id: cord-278569-yr06jwm1 author: Karnam, Guruswamy title: CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection date: 2012-05-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(−/−) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R. url: https://doi.org/10.1371/journal.ppat.1002710 doi: 10.1371/journal.ppat.1002710 id: cord-342825-s8ddek2f author: Kim, Ye Ji title: Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators date: 2016-08-26 words: 10236.0 sentences: 535.0 pages: flesch: 49.0 cache: ./cache/cord-342825-s8ddek2f.txt txt: ./txt/cord-342825-s8ddek2f.txt summary: RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. This result suggests that an indirect effect of virus infection on neighboring uninfected cells is responsible for the greater induction of ISG15 and protein ISGylation by HCMV than by UV-HCMV at low MOIs. Since HCMV IE1 inhibits the activation of ISRE-containing promoters by sequestering STAT2 [58] [59] [60] and PML [61] , IE1 expression may be responsible for the suppression of free ISG15 and ISG15 conjugate levels during HCMV infection. In addition to IE1, the presence of additional viral functions that downregulate protein ISGylation was prompted by our observation that UV-HCMV infection resulted in a higher level of ISG15 conjugates than IE1-deleted mutant virus at late times (Fig 2B) . abstract: Interferon-stimulated gene 15 (ISG15) encodes an ubiquitin-like protein that covalently conjugates protein. Protein modification by ISG15 (ISGylation) is known to inhibit the replication of many viruses. However, studies on the viral targets and viral strategies to regulate ISGylation-mediated antiviral responses are limited. In this study, we show that human cytomegalovirus (HCMV) replication is inhibited by ISGylation, but the virus has evolved multiple countermeasures. HCMV-induced ISG15 expression was mitigated by IE1, a viral inhibitor of interferon signaling, however, ISGylation was still strongly upregulated during virus infection. RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. A viral regulator pUL26 was found to interact with ISG15, UBE1L, and Herc5, and be ISGylated. ISGylation of pUL26 regulated its stability and inhibited its activities to suppress NF-κB signaling and complement the growth of UL26-null mutant virus. Moreover, pUL26 reciprocally suppressed virus-induced ISGylation independent of its own ISGylation. Consistently, ISGylation was more pronounced in infections with the UL26-deleted mutant virus, whose growth was more sensitive to IFNβ treatment than that of the wild-type virus. Therefore, pUL26 is a viral ISG15 target that also counteracts ISGylation. Our results demonstrate that ISGylation inhibits HCMV growth at multiple steps and that HCMV has evolved countermeasures to suppress ISG15 transcription and protein ISGylation, highlighting the importance of the interplay between virus and ISGylation in productive viral infection. url: https://doi.org/10.1371/journal.ppat.1005850 doi: 10.1371/journal.ppat.1005850 id: cord-280621-tph5n7ak author: Kim, Yunjeong title: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor date: 2016-03-30 words: 7417.0 sentences: 354.0 pages: flesch: 52.0 cache: ./cache/cord-280621-tph5n7ak.txt txt: ./txt/cord-280621-tph5n7ak.txt summary: Shifts in tissue or cell tropism and resulting changes in virulence have also been reported for coronaviruses; porcine respiratory coronavirus causes mild respiratory infection in pigs and presumably arose from transmissible gastroenteritis virus (TGEV), the etiologic agent of gastroenteritis in young pigs with a high fatality, by spontaneous mutations and/or deletions in its genome [9] . Effective treatment intervention for coronavirus infections with an immunopathological component, such as SARS, MERS and FIP, is speculated to involve the judicious use of immunomodulatory agents to enhance protective host immunity and decrease pathological immune responses and antiviral drugs to directly inhibit viral replication. These results on viral titers show that FIPV 3CLpro is a valid target for FIPV antiviral drugs and GC376 can effectively reduce the virus load in the macrophages from the ascites and the omentum of cats with FIP. abstract: Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans. url: https://www.ncbi.nlm.nih.gov/pubmed/27027316/ doi: 10.1371/journal.ppat.1005531 id: cord-343221-e29of29o author: Kindler, Eveline title: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date: 2017-02-03 words: 7896.0 sentences: 423.0 pages: flesch: 51.0 cache: ./cache/cord-343221-e29of29o.txt txt: ./txt/cord-343221-e29of29o.txt summary: Specifically, we show that genetically engineered mutants of mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E), respectively, that encode an EndoU active-site substitution known to abolish nucleolytic activity, were severely attenuated and elicited an immediate and simultaneous activation of host cell dsRNA sensors. The severe attenuation of MHV H277A and HCoV-229E H250A replication in wild-type murine and human macrophages, respectively, precluded the use of primary macrophages to assess the sensitivity of EndoU-deficient coronaviruses to IFN-I pre-treatment. Our data suggest that direct restriction of replication of EndoU-deficient coronaviruses is mediated by RNase L-mediated RNA degradation and inhibition of host cell translation through activation of PKR. Notably, also in this case Xrn1 is required to further process the de-capped mRNAs. Our data show that early during coronavirus infection the EndoU activity conceptually fulfils the same task, namely the removal of dsRNA that would otherwise trigger host cell dsRNA responses, such as IFN-β expression and activation of PKR and OAS/RNase L. abstract: Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses. url: https://www.ncbi.nlm.nih.gov/pubmed/28158275/ doi: 10.1371/journal.ppat.1006195 id: cord-004428-ob5igsv5 author: Kizziah, James L. title: Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage date: 2020-02-18 words: 8039.0 sentences: 366.0 pages: flesch: 56.0 cache: ./cache/cord-004428-ob5igsv5.txt txt: ./txt/cord-004428-ob5igsv5.txt summary: Crystal structures have also been determined for Bacillus phage SPP1 Dit [25] and the baseplates of lactococcal phages p2 and TP901-1, which include Dit, Tal, BppU, and receptor binding proteins that are not similar to the ϕ11 RBP [23, 26] . Atomic models for MTP (gp53), Dit (gp58), RBP (gp61), and parts of Tal (gp59), FibL (gp62), FibU (gp68) and TMP (gp57) were built into either the C6 or C3 baseplate reconstructions, using I-TASSER models as starting points [29] , complemented with real-space refinement in PHENIX [30] . RBP is a trimeric protein consisting of four domains: an N-terminal α-helical coiled-coil "stem" domain (residues 1-142) that is folded by 155˚at a central hinge; a fivebladed β-propeller "platform" domain (residues 143-442) that was previously suggested to bind to the GlcNAc residues of WTA on the host cell surface [21, 24] ; and two highly similar C-terminal "tower" domains (residues 443-636; S1 Table) , each consisting of a bent β-sheet superposed by an α-helix (Fig 5A) . abstract: Staphylococcus aureus is a common cause of infections in humans. The emergence of virulent, antibiotic-resistant strains of S. aureus is a significant public health concern. Most virulence and resistance factors in S. aureus are encoded by mobile genetic elements, and transduction by bacteriophages represents the main mechanism for horizontal gene transfer. The baseplate is a specialized structure at the tip of bacteriophage tails that plays key roles in host recognition, cell wall penetration, and DNA ejection. We have used high-resolution cryo-electron microscopy to determine the structure of the S. aureus bacteriophage 80α baseplate at 3.75 Å resolution, allowing atomic models to be built for most of the major tail and baseplate proteins, including two tail fibers, the receptor binding protein, and part of the tape measure protein. Our structure provides a structural basis for understanding host recognition, cell wall penetration and DNA ejection in viruses infecting Gram-positive bacteria. Comparison to other phages demonstrates the modular design of baseplate proteins, and the adaptations to the host that take place during the evolution of staphylococci and other pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048315/ doi: 10.1371/journal.ppat.1008314 id: cord-000578-jhetyd9t author: Kovalev, Nikolay title: A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis date: 2012-02-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV). To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p. The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase. We also find that Ded1p is a component of the tombusvirus replicase complex and Ded1p binds to the 3′-end of the viral minus-stranded RNA. The data obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p unwinds local structures at the 3′-end of the TBSV (−)RNA, rendering the RNA compatible for initiation of (+)-strand synthesis. Interestingly, we find that Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis. Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins. In addition, we have developed an in vitro assay for Flock house virus (FHV), a small RNA virus of insects, that also demonstrated positive effect on FHV replicase activity by the added Ded1p helicase. Thus, two small RNA viruses, which do not code for their own helicases, seems to recruit a host RNA helicase to aid their replication in infected cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280988/ doi: 10.1371/journal.ppat.1002537 id: cord-001257-t21l6i3f author: Kovalev, Nikolay title: The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication date: 2014-04-17 words: 10621.0 sentences: 624.0 pages: flesch: 58.0 cache: ./cache/cord-001257-t21l6i3f.txt txt: ./txt/cord-001257-t21l6i3f.txt summary: Novel pro-viral function of AtRH2, AtRH5 and the yeast Dbp3p and Fal1p is to bind to the viral replication enhancer present in the tombusvirus minus-strand RNA To test if AtRH2, AtRH5 and the yeast Dbp3p and Fal1p play a comparable role with the previously analyzed yeast Ded1p (human DDX3-like) and Dbp2p (human p68-like) and the ortologous AtRH20 DEAD-box helicases [30, 49] , first we performed in vitro RNA binding experiments with affinity-purified recombinant helicase proteins. The replication process leads to the production of abundant (+)RNA progeny, while the (2)RNA templates are likely sequestered in dsRNA forms within the VRCs. The presented in vitro data based on the solubilized/purified tombusvirus replicase and the CFE assay containing the membrane-bound VRC indicate that the eIF4AIIIlike RNA helicases can mainly stimulate TBSV (+)-strand synthesis, while their effects on (2)RNA synthesis have not been observed (not shown). abstract: Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990711/ doi: 10.1371/journal.ppat.1004051 id: cord-000933-nn9gj0z1 author: Krzyzaniak, Magdalena Anna title: Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein date: 2013-04-11 words: 10347.0 sentences: 569.0 pages: flesch: 54.0 cache: ./cache/cord-000933-nn9gj0z1.txt txt: ./txt/cord-000933-nn9gj0z1.txt summary: To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. To determine the pathway of RSV entry into HeLa and A549 cells, we developed quantitative fluorescence-activated cell sorting (FACS) assays and complemented them with confocal microscopy to monitor cell binding of RSV, endocytosis, fusion, and infection. Since we did not detect free capsids that would stain only for N or P (data not shown), we used the presence of the capsid antigens to distinguish between intact RSVs and VLPs. When purified virus preparations were incubated with HeLa cells at 4uC, immunoblotting after SDS-PAGE showed that more than half of the input N and P associated with the cells indicating that RSV binding in the cold was efficient (Fig. 1C) . abstract: Respiratory Syncytial Virus (RSV) is a highly pathogenic member of the Paramyxoviridae that causes severe respiratory tract infections. Reports in the literature have indicated that to infect cells the incoming viruses either fuse their envelope directly with the plasma membrane or exploit clathrin-mediated endocytosis. To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. A variety of perturbants were employed to characterize the cellular processes involved. We found that immediately after binding to cells RSV activated a signaling cascade involving the EGF receptor, Cdc42, PAK1, and downstream effectors. This led to a series of dramatic actin rearrangements; the cells rounded up, plasma membrane blebs were formed, and there was a significant increase in fluid uptake. If these effects were inhibited using compounds targeting Na(+)/H(+) exchangers, myosin II, PAK1, and other factors, no infection was observed. The RSV was rapidly and efficiently internalized by an actin-dependent process that had all hallmarks of macropinocytosis. Rather than fusing with the plasma membrane, the viruses thus entered Rab5-positive, fluid-filled macropinosomes, and fused with the membranes of these on the average 50 min after internalization. Rab5 was required for infection. To find an explanation for the endocytosis requirement, which is unusual among paramyxoviruses, we analyzed the fusion protein, F, and could show that, although already cleaved by a furin family protease once, it underwent a second, critical proteolytic cleavage after internalization. This cleavage by a furin-like protease removed a small peptide from the F1 subunits, and made the virus infectious. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623752/ doi: 10.1371/journal.ppat.1003309 id: cord-013526-6fip93l2 author: Labadie, Thomas title: A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion date: 2020-10-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Recent developments on extracellular vesicles (EVs) containing multiple virus particles challenge the rigid definition of non-enveloped viruses. However, how non-enveloped viruses hijack cell machinery to promote non-lytic release in EVs, and their functional roles, remain to be clarified. Here we used Bluetongue virus (BTV) as a model of a non-enveloped arthropod-borne virus and discovered that the majority of viruses are released in EVs. Based on the cellular proteins detected in these EVs, and use of inhibitors targeting the cellular degradation process, we demonstrated that these extracellular vesicles are derived from secretory lysosomes, in which the acidic pH is neutralized upon the infection. Moreover, we report that secreted EVs are more efficient than free-viruses for initiating infections, but that they trigger super-infection exclusion that only free-viruses can overcome. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595637/ doi: 10.1371/journal.ppat.1009015 id: cord-076082-4kpkhz0o author: Lam, Tommy Tsan-Yuk title: Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia date: 2008-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515348/ doi: 10.1371/journal.ppat.1000130 id: cord-000318-wk2u2a9w author: Lamb, Daniel title: Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins date: 2011-02-03 words: 7494.0 sentences: 317.0 pages: flesch: 47.0 cache: ./cache/cord-000318-wk2u2a9w.txt txt: ./txt/cord-000318-wk2u2a9w.txt summary: Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry. The BLV crystal structure and our analysis of HTLV-1 and BLV envelope-mediated membrane fusion reveal an important role for electrostatic interactions in binding of the LHR to the grooves of the coiled coil. abstract: Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033372/ doi: 10.1371/journal.ppat.1001268 id: cord-353353-njvalb44 author: Lau, Susanna K. P. title: Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model date: 2016-10-13 words: 6982.0 sentences: 314.0 pages: flesch: 44.0 cache: ./cache/cord-353353-njvalb44.txt txt: ./txt/cord-353353-njvalb44.txt summary: Analysis of 13 complete genome sequences showed that "Rosavirus B" and "Rosavirus C" represent two potentially novel picornavirus species infecting different rodents. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Rosavirus C isolated from cell culture causes multisystemic diseases in a mouse model, with histopathological changes and positive viral antigen expression in lungs and liver of infected mice. A total of 13 complete genomes from samples of four different wild rodent species (chestnut spiny rat, Coxing''s white-bellied rat, roof rat and Indochinese forest rat) positive for "Rosavirus C" and one street rodent species (Norway rat) positive for "Rosavirus B" were sequenced directly from the positive respiratory or alimentary samples and characterized. Infected cell lines and tissues from challenged mice that were tested positive for rosavirus C RASM14A by RT-PCR were subject to viral load studies and immunohistochemical staining for viral VP1 protein as described previously [28, 69] . abstract: While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/27737017/ doi: 10.1371/journal.ppat.1005911 id: cord-324928-cpryxa6p author: Lello, Laura Sandra title: Cross-utilisation of template RNAs by alphavirus replicases date: 2020-09-04 words: 13762.0 sentences: 646.0 pages: flesch: 50.0 cache: ./cache/cord-324928-cpryxa6p.txt txt: ./txt/cord-324928-cpryxa6p.txt summary: The differences between outgroup viruses and those belonging to the SFV complex had an impact on the design of the template RNAs. The 5'' region of the CHIKV genome contains seven SL structures that affect genome replication in mammalian and/or mosquito cells [33] . Cross-utilisation of template RNAs by alphavirus replicases structures can be predicted for RNAs of other members of the SFV complex (S1 Fig), the 5'' ends of the template RNAs of SFV, MAYV, RRV and ONNV had an identical design to that of the previously constructed CHIKV template, i.e. the 5'' UTR was followed by 231nt encoding the N-terminus of nsP1 [43] . The levels of Fluc and Gluc expression in human cells, transfected with plasmids expressing template RNA and corresponding polymerase negative control replicase (P1234 GAA ), were similar for trans-replicases derived from different viruses and the same was observed for Ae albopictus cells. abstract: Most alphaviruses (family Togaviridae) including Sindbis virus (SINV) and other human pathogens, are transmitted by arthropods. The first open reading frame in their positive strand RNA genome encodes for the non-structural polyprotein, a precursor to four separate subunits of the replicase. The replicase interacts with cis-acting elements located near the intergenic region and at the ends of the viral RNA genome. A trans-replication assay was developed and used to analyse the template requirements for nine alphavirus replicases. Replicases of alphaviruses of the Semliki Forest virus complex were able to cross-utilize each other’s templates as well as those of outgroup alphaviruses. Templates of outgroup alphaviruses, including SINV and the mosquito-specific Eilat virus, were promiscuous; in contrast, their replicases displayed a limited capacity to use heterologous templates, especially in mosquito cells. The determinants important for efficient replication of template RNA were mapped to the 5' region of the genome. For SINV these include the extreme 5'- end of the genome and sequences corresponding to the first stem-loop structure in the 5' untranslated region. Mutations introduced in these elements drastically reduced infectivity of recombinant SINV genomes. The trans-replicase tools and approaches developed here can be instrumental in studying alphavirus recombination and evolution, but can also be applied to study other viruses such as picornaviruses, flaviviruses and coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32886709/ doi: 10.1371/journal.ppat.1008825 id: cord-331721-l5kocy4f author: Liang, Jingjing title: Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress date: 2017-01-11 words: 6595.0 sentences: 342.0 pages: flesch: 54.0 cache: ./cache/cord-331721-l5kocy4f.txt txt: ./txt/cord-331721-l5kocy4f.txt summary: Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles. Indeed, we confirmed that hypothesis by first using co-IP to validate the specificity of the PPxY/WW-domain physical interaction between VP40 (both eVP40 and mVP40) and BAG3, and functionally demonstrated that expression of BAG3 inhibited VP40 VLP production, as well as budding of a VSV recombinant virus containing the EBOV VP40 PPxY L-domain motif. abstract: Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles. url: https://doi.org/10.1371/journal.ppat.1006132 doi: 10.1371/journal.ppat.1006132 id: cord-002530-ao7kenbx author: Lin, Yao-Tang title: The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication date: 2017-05-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426786/ doi: 10.1371/journal.ppat.1006329 id: cord-294342-7ycgd0h7 author: Markosyan, Ruben M. title: Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date: 2016-01-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge—a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry. url: https://doi.org/10.1371/journal.ppat.1005373 doi: 10.1371/journal.ppat.1005373 id: cord-000729-iq30z094 author: Marsh, Glenn A. title: Cedar Virus: A Novel Henipavirus Isolated from Australian Bats date: 2012-08-02 words: 6101.0 sentences: 277.0 pages: flesch: 49.0 cache: ./cache/cord-000729-iq30z094.txt txt: ./txt/cord-000729-iq30z094.txt summary: The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrinB2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. As part of our on-going field studies on HeV genetic diversity and infection dynamics in the Queensland flying fox populations, urine samples were collected on a regular basis for PCR and virus isolation. CedPV is more closely related to HeV and NiV than henipavirus-like sequences detected in African bats [26, 32] as shown in a phylogenetic tree based on the only sequences available of a 550-nt L gene fragment (Fig. S5) . abstract: The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural reservoir. Each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. Here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV), which shares significant features with the known henipaviruses. The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrin- B2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. In this context, it is interesting to note that the major genetic difference between CedPV and HeV or NiV lies within the coding strategy of the P gene, which is known to play an important role in evading the host innate immune system. Unlike HeV, NiV, and almost all known paramyxoviruses, the CedPV P gene lacks both RNA editing and also the coding capacity for the highly conserved V protein. Preliminary study indicated that CedPV infection of human cells induces a more robust IFN-β response than HeV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410871/ doi: 10.1371/journal.ppat.1002836 id: cord-266078-h53zpjab author: McGuckin Wuertz, Kathryn title: STING is required for host defense against neuropathological West Nile virus infection date: 2019-08-15 words: 9796.0 sentences: 470.0 pages: flesch: 49.0 cache: ./cache/cord-266078-h53zpjab.txt txt: ./txt/cord-266078-h53zpjab.txt summary: Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. In vivo, STING-/mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. In the CNS however, we observed a trend toward increased viral RNA and innate immune gene expression at 8 dpi in WNV-infected STING-/-mice, similar to that observed in BMDM (Fig 3A and 3D) . These observations suggest that STING plays a role in directing or maintaining the T cell response to specific loci within the CNS or that initial viral infection led to increased STING is required for host defense against neuropathological West Nile virus infection recruitment of a localized adaptive immune response that resulted in immunopathology. abstract: West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease. url: https://www.ncbi.nlm.nih.gov/pubmed/31415679/ doi: 10.1371/journal.ppat.1007899 id: cord-002893-d7hetoq0 author: Meng, Xiangzhi title: A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection date: 2018-02-15 words: 6300.0 sentences: 322.0 pages: flesch: 52.0 cache: ./cache/cord-002893-d7hetoq0.txt txt: ./txt/cord-002893-d7hetoq0.txt summary: Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. Both paralogs are antagonized by VACV K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is resistant to the C7 homolog encoded by a group of poxviruses with a narrow host range in ruminants, indicating that host species-specific difference in SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission. VACV K1, C7 and C7 homologs from diverse poxviruses could overcome hSAMD9L restriction, but the sheeppox virus C7 homolog has reduced potency due to the variation of two residues To find out whether mammalian poxviruses could overcome the restriction of hSAMD9L, we induced hSAMD9L expression in ΔhSAMD9 HeLa cells with 200 U/ml of IFN-β and then infected the cells with our panel of vK1L -C7L --derived VACVs. Viruses that expressed VACV-K1, VACV-C7, MYXV-M62, SPPV-063, SWPV-064 and YLDV-67 (but not MYXV-M63 and MYXV-M64) grew in IFN-treated ΔhSAMD9 cells (Fig 5A) , indicating that all known SAMD9 antagonists could also antagonize hSAMD9L. abstract: Host restriction factors constitute a formidable barrier for viral replication to which many viruses have evolved counter-measures. Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. A paralog of SAMD9, SAMD9L, is also encoded by some mammals, while only one of two paralogs is retained by others. Here, we show that SAMD9L functions similarly to SAMD9 as a restriction factor and that the two paralogs form a critical host barrier that poxviruses must overcome to establish infection. In mice, which naturally lack SAMD9, overcoming SAMD9L restriction with viral inhibitors is essential for poxvirus replication and pathogenesis. While a VACV deleted of both K1 and C7 (vK1L(-)C7L(-)) was restricted by mouse cells and highly attenuated in mice, its replication and virulence were completely restored in SAMD9L(-/-) mice. In humans, both SAMD9 and SAMD9L are poxvirus restriction factors, although the latter requires interferon induction in many cell types. While knockout of SAMD9 with Crispr-Cas9 was sufficient for abolishing the restriction for vK1L(-)C7L(-) in many human cells, knockout of both paralogs was required for abolishing the restriction in interferon-treated cells. Both paralogs are antagonized by VACV K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is resistant to the C7 homolog encoded by a group of poxviruses with a narrow host range in ruminants, indicating that host species-specific difference in SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831749/ doi: 10.1371/journal.ppat.1006884 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: nan sentences: nan pages: flesch: nan cache: txt: summary: 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: nan sentences: nan pages: flesch: nan cache: txt: summary: 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-280221-s6oxq772 author: Montelongo-Jauregui, Daniel title: Convalescent serum therapy for COVID-19: A 19th century remedy for a 21st century disease date: 2020-08-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32785259/ doi: 10.1371/journal.ppat.1008735 id: cord-334315-ymkrgj0h author: Moon, Stephanie L. title: Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine date: 2013-12-05 words: 1995.0 sentences: 100.0 pages: flesch: 43.0 cache: ./cache/cord-334315-ymkrgj0h.txt txt: ./txt/cord-334315-ymkrgj0h.txt summary: This review describes the myriad ways that viruses deal with the general host RNA decay machinery that is active in the cell immediately upon viral infection-turning what, at first, appears to be very hostile territory for a foreign transcript into a sort of ''''promised land'''' for viral gene expression. Disparate RNA viruses have, therefore, evolved unique mechanisms by which they disarm host RNA decay pathways by inactivating or proteolytically degrading important nucleases to promote productive viral infections. In addition, to make a cell more amenable to virus production, these virally encoded nucleases may also create a new ''''sandbox'''' in the cytoplasm for viral RNAs by initiating the large-scale decay of cellular mRNAs and dramatically altering the landscape of host gene expression. Considering the importance of RNA stability in regulating transcript abundance, the inactivation or commandeering of cellular RNA decay factors by viruses is likely to significantly alter host gene expression. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/24339774/ doi: 10.1371/journal.ppat.1003762 id: cord-310509-c8wp2m69 author: Morens, David M. title: Emerging Infectious Diseases: Threats to Human Health and Global Stability date: 2013-07-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/23853589/ doi: 10.1371/journal.ppat.1003467 id: cord-346053-mk1mzc5z author: Morris, Cindy E. title: Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries date: 2009-12-24 words: 4758.0 sentences: 262.0 pages: flesch: 39.0 cache: ./cache/cord-346053-mk1mzc5z.txt txt: ./txt/cord-346053-mk1mzc5z.txt summary: We present numerous examples of virulence traits in plant pathogenic microorganisms that also have a function in their survival and growth in nonagricultural and nonplant habitats. Adaptation to biotic and abiotic stresses, within or outside of agricultural habitats, likely plays as important a role in the evolution of parasitic fitness of plant pathogens as it does for human pathogens. As illustrated above, traits that confer fitness in response to biotic and abiotic environmental stress can have dual-use as virulence factors in human pathogens. In plant pathogens, the transport systems for toxins and antimicrobials can have broad spectrum activity, leading to resistance to agricultural fungicides and also contributing to virulence [12] . The examples listed above that describe traits that play roles in both environmental fitness and virulence to plants provide a compelling incentive to expand our paradigms concerning the forces that drive evolution of plant pathogenicity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/20041212/ doi: 10.1371/journal.ppat.1000693 id: cord-341034-2oigu75k author: Moser, Theresa S. title: AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis date: 2012-04-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism. url: https://doi.org/10.1371/journal.ppat.1002661 doi: 10.1371/journal.ppat.1002661 id: cord-262753-jld1ygxt author: Neidermyer, William J. title: Global analysis of polysome-associated mRNA in vesicular stomatitis virus infected cells date: 2019-06-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Infection of mammalian cells with vesicular stomatitis virus (VSV) results in the inhibition of cellular translation while viral translation proceeds efficiently. VSV RNA synthesis occurs entirely within the cytoplasm, where during transcription the viral polymerase produces 5 mRNAs that are structurally indistinct to cellular mRNAs with respect to their 5′ cap-structure and 3′-polyadenylate tail. Using the global approach of massively parallel sequencing of total cytoplasmic, monosome- and polysome-associated mRNA, we interrogate the impact of VSV infection of HeLa cells on translation. Analysis of sequence reads in the different fractions shows >60% of total cytoplasmic and polysome-associated reads map to the 5 viral genes by 6 hours post-infection, a time point at which robust host cell translational shut-off is observed. Consistent with an overwhelming abundance of viral mRNA in the polysome fraction, the reads mapping to cellular genes were reduced. The cellular mRNAs that remain most polysome-associated following infection had longer half-lives, were typically larger, and were more AU rich, features that are shared with the viral mRNAs. Several of those mRNAs encode proteins known to positively affect viral replication, and using chemical inhibition and siRNA depletion we confirm that the host chaperone heat shock protein 90 (hsp90) and eukaryotic translation initiation factor 3A (eIF3A)—encoded by 2 such mRNAs—support viral replication. Correspondingly, regulated in development and DNA damage 1 (Redd1) encoded by a host mRNA with reduced polysome association inhibits viral infection. These data underscore the importance of viral mRNA abundance in the shut-off of host translation in VSV infected cells and link the differential translatability of some cellular mRNAs with pro- or antiviral function. url: https://www.ncbi.nlm.nih.gov/pubmed/31226162/ doi: 10.1371/journal.ppat.1007875 id: cord-000018-amvlm09p author: Pauli, Eva-K. title: Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression date: 2008-11-07 words: 9011.0 sentences: 515.0 pages: flesch: 53.0 cache: ./cache/cord-000018-amvlm09p.txt txt: ./txt/cord-000018-amvlm09p.txt summary: Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. These results are consistent with data gained from previous experiments in Vero cells ( Figure 1E ) and indicate that neither induction of SOCS-3 mRNA nor inhibition of STAT phosphorylation is dependent on virus-induced type I IFN expression. To answer the question whether enhanced STAT phosphorylation in SOCS-3 deficient cells would also lead to enhanced expression of ISGs, total RNA was isolated at different time points p.i. from infected wild type and knock out cells and monitored for induction of SP110, IRF-1 and OAS1 ( Figure 7E, 7F and 7G ). abstract: The type I interferon (IFN) system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNβ gene induction via action of the viral non-structural protein 1 (NS1). Here we present data indicating that influenza A viruses not only suppress IFNβ gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3) protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5′ triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK)/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-κB)-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572141/ doi: 10.1371/journal.ppat.1000196 id: cord-351952-lhhjax3s author: Pickering, Suzanne title: Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings date: 2020-09-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays—a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)—on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections. url: https://doi.org/10.1371/journal.ppat.1008817 doi: 10.1371/journal.ppat.1008817 id: cord-290617-45be6gxe author: Poulain, Florian title: Footprint of the host restriction factors APOBEC3 on the genome of human viruses date: 2020-08-14 words: 10515.0 sentences: 610.0 pages: flesch: 56.0 cache: ./cache/cord-290617-45be6gxe.txt txt: ./txt/cord-290617-45be6gxe.txt summary: Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. By breaking down the human viruses into their respective Baltimore''s group (S3 Fig), we observed that NTC depletion is not present in reverse transcribing nor in negative sense single strand RNA viruses. We also observed a mild general NCC depletion in single strand DNA and double strand RNA viruses, justifying further investigation for a possible A3G-induced footprint (S1 Fig). In order to identify A3-footprinted viruses, we detailed the NTC and NNGANN ratios for 870 human viral species (Fig 4A) . B. The observed/expected ratios of TC dinucleotide at various codon positions and on both strands (i.e. NNTCNN, TCN, NTC, GAN, NGA and NNGANN) were calculated for the putative A3-footprinted viral species and depicted by a heatmap. abstract: APOBEC3 enzymes are innate immune effectors that introduce mutations into viral genomes. These enzymes are cytidine deaminases which transform cytosine into uracil. They preferentially mutate cytidine preceded by thymidine making the 5’TC motif their favored target. Viruses have evolved different strategies to evade APOBEC3 restriction. Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. Hence, the APOBEC3s left on the genome of certain viruses an evolutionary footprint. The aim of our study is the identification of these viruses having a genome shaped by the APOBEC3s. We analyzed the genome of 33,400 human viruses for the depletion of APOBEC3-favored motifs. We demonstrate that the APOBEC3 selection pressure impacts at least 22% of all currently annotated human viral species. The papillomaviridae and polyomaviridae are the most intensively footprinted families; evidencing a selection pressure acting genome-wide and on both strands. Members of the parvoviridae family are differentially targeted in term of both magnitude and localization of the footprint. Interestingly, a massive APOBEC3 footprint is present on both strands of the B19 erythroparvovirus; making this viral genome one of the most cleaned sequences for APOBEC3-favored motifs. We also identified the endemic coronaviridae as significantly footprinted. Interestingly, no such footprint has been detected on the zoonotic MERS-CoV, SARS-CoV-1 and SARS-CoV-2 coronaviruses. In addition to viruses that are footprinted genome-wide, certain viruses are footprinted only on very short sections of their genome. That is the case for the gamma-herpesviridae and adenoviridae where the footprint is localized on the lytic origins of replication. A mild footprint can also be detected on the negative strand of the reverse transcribing HIV-1, HIV-2, HTLV-1 and HBV viruses. Together, our data illustrate the extent of the APOBEC3 selection pressure on the human viruses and identify new putatively APOBEC3-targeted viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32797103/ doi: 10.1371/journal.ppat.1008718 id: cord-303403-9th2jiq6 author: Qing, Jie title: Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator date: 2014-10-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/25275585/ doi: 10.1371/journal.ppat.1004422 id: cord-254735-8reu45yz author: Reguera, Juan title: Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies date: 2012-08-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The coronaviruses (CoVs) are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10–20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S) mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs) of two closely related CoV strains, transmissible gastroenteritis virus (TGEV) and porcine respiratory CoV (PRCV), in complex with their receptor, porcine APN (pAPN), or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs. url: https://doi.org/10.1371/journal.ppat.1002859 doi: 10.1371/journal.ppat.1002859 id: cord-002142-tdgu9sr9 author: Reniere, Michelle L. title: An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression date: 2016-07-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from a phagosome, rapid cytosolic growth, and ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA. The environmental cues that lead to temporal and spatial control of L. monocytogenes virulence gene expression are poorly understood. In this study, we took advantage of the robust up-regulation of ActA that occurs intracellularly and expressed Cre recombinase from the actA promoter and 5’ untranslated region in a strain in which loxP sites flanked essential genes, so that activation of actA led to bacterial death. Upon screening for transposon mutants that survived intracellularly, six genes were identified as necessary for ActA expression. Strikingly, most of the genes, including gshF, spxA1, yjbH, and ohrA, are predicted to play important roles in bacterial redox regulation. The mutants identified in the genetic selection fell into three broad categories: (1) those that failed to reach the cytosolic compartment; (2) mutants that entered the cytosol, but failed to activate the master virulence regulator PrfA; and (3) mutants that entered the cytosol and activated transcription of actA, but failed to synthesize it. The identification of mutants defective in vacuolar escape suggests that up-regulation of ActA occurs in the host cytosol and not the vacuole. Moreover, these results provide evidence for two non-redundant cytosolic cues; the first results in allosteric activation of PrfA via increased glutathione levels and transcriptional activation of actA while the second results in translational activation of actA and requires yjbH. Although the precise host cues have not yet been identified, we suggest that intracellular redox stress occurs as a consequence of both host and pathogen remodeling their metabolism upon infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945081/ doi: 10.1371/journal.ppat.1005741 id: cord-001385-rb5vwolt author: Reuven, Eliran Moshe title: The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses date: 2014-08-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133399/ doi: 10.1371/journal.ppat.1004248 id: cord-314451-mqnqjn0c author: Roberts, Anjeanette title: A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date: 2007-01-12 words: 9794.0 sentences: 433.0 pages: flesch: 48.0 cache: ./cache/cord-314451-mqnqjn0c.txt txt: ./txt/cord-314451-mqnqjn0c.txt summary: To generate a model that satisfies these criteria, we have serially passaged SARS-CoV in the respiratory tract of young BALB/c mice, resulting in a lethal virus that causes dosedependent weight loss and mortality associated with higher viral titers in the respiratory tract than are seen with the wildtype virus and with histopathologic findings of severe pulmonary disease. Northern blot analysis of RNA from infected Vero E6 cells indicated that genomic vRNA and viral mRNA and all eight sub-genomic mRNAs were present in similar ratios for the recombinant viruses and MA15 virus as for SARS-CoV (Urbani) ( Figure 2A ). In order to evaluate whether changes in tissue tropism or levels of viral replication could contribute to the lethal phenotype of the MA15 virus, viral titers in lungs, spleen, liver, and brain of BALB/c mice were determined at various time points following intranasal inoculation with SARS-CoV (Urbani) or MA15. abstract: No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals. url: https://www.ncbi.nlm.nih.gov/pubmed/17222058/ doi: 10.1371/journal.ppat.0030005 id: cord-290253-hxxizipk author: Roberts, Katherine E. title: Changes in temperature alter the potential outcomes of virus host shifts date: 2018-10-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Host shifts–where a pathogen jumps between different host species–are an important source of emerging infectious disease. With on-going climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, while the mean viral load did not. This suggests that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures, and proxies for thermal optima (critical thermal maximum and minimum or basal metabolic rate). These results suggest that whilst the rank order of species susceptibilities may remain the same with changes in temperature, some species may become more susceptible to a novel pathogen, and others less so. url: https://doi.org/10.1371/journal.ppat.1007185 doi: 10.1371/journal.ppat.1007185 id: cord-334947-pa0p5dif author: Rozen-Gagnon, Kathryn title: Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models date: 2014-01-16 words: 8887.0 sentences: 415.0 pages: flesch: 44.0 cache: ./cache/cord-334947-pa0p5dif.txt txt: ./txt/cord-334947-pa0p5dif.txt summary: Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. To estimate the population diversity of variants by deep sequencing, cDNA libraries were prepared by Superscript III from RNA extracted from virus generated in BHK-21 or C6/36 cells, and the viral genome was amplified using a high fidelity polymerase (Phusion) to generate 5 overlapping amplicons 2-3 kb in length. To address the possibility that the fitness cost of defective replication, observed in mosquito cell culture, would favor the reversion of these mutant polymerases to wildtype, we deep sequenced virus from the body of an individual mosquito that presented the median titer from each group. abstract: Arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. To study the genetic mechanisms and determinants of these processes, we use chikungunya virus (CHIKV), a re-emerging human pathogen transmitted by the Aedes mosquito. We previously isolated a high fidelity (or antimutator) polymerase variant, C483Y, which had decreased fitness in both mammalian and mosquito hosts, suggesting this residue may be a key molecular determinant. To further investigate effects of position 483 on RNA-dependent RNA-polymerase (RdRp) fidelity, we substituted every amino acid at this position. We isolated novel mutators with decreased replication fidelity and higher mutation frequencies, allowing us to examine the fitness of error-prone arbovirus variants. Although CHIKV mutators displayed no major replication defects in mammalian cell culture, they had reduced specific infectivity and were attenuated in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and the variants exhibited significant defects in RNA synthesis. Consequently, these replication defects resulted in strong selection for reversion during infection of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. However, replication defects were mosquito cell-specific and were not observed in Drosophila S2 cells, allowing us to evaluate the potential attenuation of mutators in insect models where pressure for reversion was absent. Indeed, the SINV mutator variant was attenuated in fruit flies. These findings confirm that residue 483 is a determinant regulating alphavirus polymerase fidelity and demonstrate proof of principle that arboviruses can be attenuated in mammalian and insect hosts by reducing fidelity. url: https://www.ncbi.nlm.nih.gov/pubmed/24453971/ doi: 10.1371/journal.ppat.1003877 id: cord-286072-kgpvdb42 author: Sa Ribero, Margarida title: Interplay between SARS-CoV-2 and the type I interferon response date: 2020-07-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2–infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I–producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection. url: https://doi.org/10.1371/journal.ppat.1008737 doi: 10.1371/journal.ppat.1008737 id: cord-356115-vblgotjn author: Sawicki, Stanley G title: Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins date: 2005-12-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mRNAs in the virus-infected cell. Here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of Murine hepatitis virus MHV-A59 that are unable to synthesize viral RNA when the infection is initiated and maintained at the non-permissive temperature. Both classical and biochemical complementation analysis leads us to predict that the majority of MHV-A59 ORF1a replicase gene products (non-structural proteins nsp1–nsp11) form a single complementation group (cistron1) while the replicase gene products encoded in ORF1b (non-structural proteins nsp12–nsp16) are able to function in trans and comprise at least three, and possibly five, further complementation groups (cistrons II–VI). Also, we have identified mutations in the non-structural proteins nsp 4, nsp5, nsp10, nsp12, nsp14, and nsp16 that are responsible for the ts phenotype of eight MHV-A59 mutants, which allows us to conclude that these proteins are essential for the assembly of a functional replicase-transcriptase complex. Finally, our analysis of viral RNA synthesis in ts mutant virus-infected cells allows us to discriminate three phenotypes with regard to the inability of specific mutants to synthesize viral RNA at the non-permissive temperature. Mutant LA ts6 appeared to be defective in continuing negative-strand synthesis, mutant Alb ts16 appeared to form negative strands but these were not utilized for positive-strand RNA synthesis, and mutant Alb ts22 was defective in the elongation of both positive- and negative-strand RNA. On the basis of these results, we propose a model that describes a pathway for viral RNA synthesis in MHV-A59-infected cells. Further biochemical analysis of these mutants should allow us to identify intermediates in this pathway and elucidate the precise function(s) of the viral replicase proteins involved. url: https://www.ncbi.nlm.nih.gov/pubmed/16341254/ doi: 10.1371/journal.ppat.0010039 id: cord-355839-o0m71kvw author: Sedeyn, Koen title: Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date: 2019-10-17 words: 8187.0 sentences: 414.0 pages: flesch: 45.0 cache: ./cache/cord-355839-o0m71kvw.txt txt: ./txt/cord-355839-o0m71kvw.txt summary: ATF2, activating transcription factor 2; CDS, cytoplasmic DNA sensor; ER, endoplasmic reticulum; IFN, interferon; IKK, inhibitor of nuclear factor kappa-B kinase; IKKε, inhibitor of nuclear factor kappa-B kinase subunit epsilon; IRF3, interferon regulatory factor 3; IRF7, interferon regulatory factor 7; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAVS, mitochondrial antiviral-signaling protein; MDA5, melanoma differentiation-associated protein 5; MyD88, myeloid differentiation primary response protein MyD88; NF-kB, nuclear factor-kappa B; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PAMP, pathogenassociated molecular pattern; PRR, pattern recognition receptor; RIG, retinoic-acid-inducible gene-I; RLR, RIG-I-like receptor; RSV, respiratory syncytial virus; STING, stimulator of interferon protein; TBK1, tank binding kinase 1; TICAM1, toll/interleukin-1 receptor domain-containing adapter molecule 1; TIRAP, toll/ interleukin-1 receptor domain-containing adapter protein; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptor-associated factor 3; TRAF6, tumor necrosis factor receptor-associated factor 6; TRAM, toll-like receptor adaptor molecule. abstract: Human respiratory syncytial virus (RSV) is the most important cause of acute lower respiratory tract disease in infants worldwide. As a first line of defense against respiratory infections, innate immune responses, including the production of type I and III interferons (IFNs), play an important role. Upon infection with RSV, multiple pattern recognition receptors (PRRs) can recognize RSV-derived pathogen-associated molecular patterns (PAMPs) and mount innate immune responses. Retinoic-acid-inducible gene-I (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) have been identified as important innate receptors to mount type I IFNs during RSV infection. However, type I IFN levels remain surprisingly low during RSV infection despite strong viral replication. The poor induction of type I IFNs can be attributed to the cooperative activity of 2 unique, nonstructural (NS) proteins of RSV, i.e., NS1 and NS2. These viral proteins have been shown to suppress both the production and signaling of type I and III IFNs by counteracting a plethora of key host innate signaling proteins. Moreover, increasing numbers of IFN-stimulated genes (ISGs) are being identified as targets of the NS proteins in recent years, highlighting an underexplored protein family in the identification of NS target proteins. To understand the diverse effector functions of NS1 and NS2, Goswami and colleagues proposed the hypothesis of the NS degradasome (NSD) complex, a multiprotein complex made up of, at least, NS1 and NS2. Furthermore, the crystal structure of NS1 was resolved recently and, remarkably, identified NS1 as a structural paralogue of the RSV matrix protein. Unfortunately, no structural data on NS2 have been published so far. In this review, we briefly describe the PRRs that mount innate immune responses upon RSV infection and provide an overview of the various effector functions of NS1 and NS2. Furthermore, we discuss the ubiquitination effector functions of NS1 and NS2, which are in line with the hypothesis that the NSD shares features with the canonical 26S proteasome. url: https://www.ncbi.nlm.nih.gov/pubmed/31622448/ doi: 10.1371/journal.ppat.1007984 id: cord-316584-b1aa1lri author: Seiradake, Elena title: The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution date: 2009-01-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad–erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models. url: https://www.ncbi.nlm.nih.gov/pubmed/19119424/ doi: 10.1371/journal.ppat.1000277 id: cord-292424-daj4zcm1 author: Shang, Jian title: Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry date: 2020-03-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse hepatitis coronavirus (MHV) is the only known coronavirus that uses the N-terminal domain (NTD) of its spike to recognize a protein receptor, CEACAM1a. Here we determined the cryo-EM structure of MHV spike complexed with mouse CEACAM1a. The trimeric spike contains three receptor-binding S1 heads sitting on top of a trimeric membrane-fusion S2 stalk. Three receptor molecules bind to the sides of the spike trimer, where three NTDs are located. Receptor binding induces structural changes in the spike, weakening the interactions between S1 and S2. Using protease sensitivity and negative-stain EM analyses, we further showed that after protease treatment of the spike, receptor binding facilitated the dissociation of S1 from S2, allowing S2 to transition from pre-fusion to post-fusion conformation. Together these results reveal a new role of receptor binding in MHV entry: in addition to its well-characterized role in viral attachment to host cells, receptor binding also induces the conformational change of the spike and hence the fusion of viral and host membranes. Our study provides new mechanistic insight into coronavirus entry and highlights the diverse entry mechanisms used by different viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32150576/ doi: 10.1371/journal.ppat.1008392 id: cord-323568-s0wmll4q author: Shang, Jian title: Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins date: 2018-04-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity. url: https://doi.org/10.1371/journal.ppat.1007009 doi: 10.1371/journal.ppat.1007009 id: cord-268388-kkhuzf3p author: Sharif-Yakan, Ahmad title: Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date: 2014-12-04 words: 2507.0 sentences: 141.0 pages: flesch: 50.0 cache: ./cache/cord-268388-kkhuzf3p.txt txt: ./txt/cord-268388-kkhuzf3p.txt summary: Two years have passed since the initial description of the Middle East respiratory syndrome coronavirus (MERS-CoV), yet the epidemic is far from being controlled. First reported in 2012 [1] , Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus and the first lineage 2C Betacoronavirus known to infect humans [2] . Middle east respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, qatar Middle east respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: A descriptive study Clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: A report of nosocomial transmission Clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: An observational study abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25474536/ doi: 10.1371/journal.ppat.1004457 id: cord-001676-68y733y3 author: Shoemaker, Jason E. title: An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation date: 2015-06-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza viruses present major challenges to public health, evident by the 2009 influenza pandemic. Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner. However, a comprehensive characterization of the complex dynamics of the inflammatory response induced by virulent influenza strains is lacking. Here, we applied gene co-expression and nonlinear regression analysis to time-course, microarray data developed from influenza-infected mouse lung to create mathematical models of the host inflammatory response. We found that the dynamics of inflammation-associated gene expression are regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal gene expression but expression is strongly induced once a threshold virus titer is exceeded. Cytokine assays confirmed that the production of several key inflammatory cytokines, such as interleukin 6 and monocyte chemotactic protein 1, exhibit ultrasensitive behavior. A systematic exploration of the pathways regulating the inflammatory-associated gene response suggests that the molecular origins of this ultrasensitive response mechanism lie within the branch of the Toll-like receptor pathway that regulates STAT1 phosphorylation. This study provides the first evidence of an ultrasensitive mechanism regulating influenza virus-induced inflammation in whole lungs and provides insight into how different virus strains can induce distinct temporal inflammation response profiles. The approach developed here should facilitate the construction of gene regulatory models of other infectious diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457877/ doi: 10.1371/journal.ppat.1004856 id: cord-264579-csro48ks author: Sigalov, Alexander B. title: Novel Mechanistic Insights into Viral Modulation of Immune Receptor Signaling date: 2009-07-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/19649322/ doi: 10.1371/journal.ppat.1000404 id: cord-002608-zn7tm1ww author: Sokoloski, Kevin J. title: Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants date: 2017-06-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection. Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production. Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity. Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection. Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection. This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507600/ doi: 10.1371/journal.ppat.1006473 id: cord-001655-uqw74ra0 author: Stenglein, Mark D. title: Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections date: 2015-05-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438980/ doi: 10.1371/journal.ppat.1004900 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-000164-094d0rn6 author: Suthar, Mehul S. title: IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity date: 2010-02-05 words: 8172.0 sentences: 340.0 pages: flesch: 44.0 cache: ./cache/cord-000164-094d0rn6.txt txt: ./txt/cord-000164-094d0rn6.txt summary: Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. To define the role of IPS-1 in controlling virus replication and innate immunity in myeloid cells, we analyzed WNV infection and host responses in primary bone marrow-derived DC and Mw recovered from wild type and IPS-1 2/2 mice. abstract: The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1(−/−) mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816698/ doi: 10.1371/journal.ppat.1000757 id: cord-264225-vzcfeh7t author: Talbert-Slagle, Kristina title: Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body date: 2014-05-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://doi.org/10.1371/journal.ppat.1004092 doi: 10.1371/journal.ppat.1004092 id: cord-311383-1aqt65cc author: Tan, Jinzhi title: The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes date: 2009-05-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUD(core)”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/19436709/ doi: 10.1371/journal.ppat.1000428 id: cord-001109-xs7df6a7 author: Tapia, Karla title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity date: 2013-10-31 words: 7169.0 sentences: 360.0 pages: flesch: 50.0 cache: ./cache/cord-001109-xs7df6a7.txt txt: ./txt/cord-001109-xs7df6a7.txt summary: We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. To further investigate the cellular mechanisms responsible for the efficient activation of the antiviral response by SeV DVGs, we evaluated the phosphorylation of transcription factors that are critical for the expression of type I IFNs in cells infected with equivalent amounts of infectious particles of a SeV strain Cantell stock containing high levels of copy-back DVGs (SeV Cantell HD) or with SeV Cantell depleted of DVGs (SeV Cantell LD). Based on the potent ability of SeV stocks containing a high content of copy-back DVGs to induce the host response to infection in vitro [23, 24, 25, 28] (Fig. 1 ) and on our prior reports of strong host responses to DVGs regardless of the presence of functional virus-encoded antagonists [23, 24] , we hypothesized that DVGs that arise in situ during viral infections provide essential stimuli to initiate an antiviral immune response. abstract: The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814336/ doi: 10.1371/journal.ppat.1003703 id: cord-002835-qaogpxy9 author: Too, Issac Horng Khit title: Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis date: 2018-01-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764453/ doi: 10.1371/journal.ppat.1006778 id: cord-003982-7v5xl1s3 author: Trus, Ivan title: Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring date: 2019-11-14 words: 10473.0 sentences: 554.0 pages: flesch: 49.0 cache: ./cache/cord-003982-7v5xl1s3.txt txt: ./txt/cord-003982-7v5xl1s3.txt summary: title: Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome. In our porcine model studies, subclinical persistent in utero infection in mid-gestation also increased interferon alpha (IFN-α) levels in fetal blood plasma and amniotic fluid, while IFN-α was below the detection limit in all control fetuses [18] . We performed a mixing test (S2 Video) on control and affected piglets at 35 days of age to identify whether subclinical in utero ZIKV infection and social stress have synergistic effects on cytokine responses in offspring. abstract: Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855438/ doi: 10.1371/journal.ppat.1008038 id: cord-000246-mlhd9zbs author: Valkenburg, Sophie A. title: Protective Efficacy of Cross-Reactive CD8(+) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold date: 2010-08-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity. Pre-existing CD8(+) T-cell immunity directed towards conserved internal viral regions can greatly ameliorate the disease. However, mutational escape within the T cell epitopes is a substantial issue for virus control and vaccine design. Although mutations can result in a loss of T cell recognition, some variants generate cross-reactive T cell responses. In this study, we used reverse genetics to modify the influenza NP(336–374) peptide at a partially-solvent exposed residue (N->A, NPN3A mutation) to assess the availability, effectiveness and mechanism underlying influenza-specific cross-reactive T cell responses. The engineered virus induced a diminished CD8(+) T cell response and selected a narrowed T cell receptor (TCR) repertoire within two Vβ regions (Vβ8.3 and Vβ9). This can be partially explained by the H-2D(b)NPN3A structure that showed a loss of several contacts between the NPN3A peptide and H-2D(b), including a contact with His155, a position known to play an important role in mediating TCR-pMHC-I interactions. Despite these differences, common cross-reactive TCRs were detected in both the naïve and immune NPN3A-specific TCR repertoires. However, while the NPN3A epitope primes memory T-cells that give an equivalent recall response to the mutant or wild-type (wt) virus, both are markedly lower than wt->wt challenge. Such decreased CD8(+) responses elicited after heterologous challenge resulted in delayed viral clearance from the infected lung. Furthermore, mice first exposed to the wt virus give a poor, low avidity response following secondary infection with the mutant. Thus, the protective efficacy of cross-reactive CD8(+) T cells recognising mutant viral epitopes depend on peptide-MHC-I structural interactions and functional avidity. Our study does not support vaccine strategies that include immunization against commonly selected cross-reactive variants with mutations at partially-solvent exposed residues that have characteristics comparable to NPN3A. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920842/ doi: 10.1371/journal.ppat.1001039 id: cord-277566-j3ehiwn9 author: Verheije, Monique H. title: Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation date: 2008-06-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronaviruses induce in infected cells the formation of double membrane vesicles, which are the sites of RNA replication. Not much is known about the formation of these vesicles, although recent observations indicate an important role for the endoplasmic reticulum in the formation of the mouse hepatitis coronavirus (MHV) replication complexes (RCs). We now show that MHV replication is sensitive to brefeldin A (BFA). Consistently, expression of a dominant-negative mutant of ARF1, known to mimic the action of the drug, inhibited MHV infection profoundly. Immunofluorescence analysis and quantitative electron microscopy demonstrated that BFA did not block the formation of RCs per se, but rather reduced their number. MHV RNA replication was not sensitive to BFA in MDCK cells, which are known to express the BFA-resistant guanine nucleotide exchange factor GBF1. Accordingly, individual knockdown of the Golgi-resident targets of BFA by transfection of small interfering RNAs (siRNAs) showed that GBF1, but not BIG1 or BIG2, was critically involved in MHV RNA replication. ARF1, the cellular effector of GBF1, also appeared to be involved in MHV replication, as siRNAs targeting this small GTPase inhibited MHV infection significantly. Collectively, our results demonstrate that GBF1-mediated ARF1 activation is required for efficient MHV RNA replication and reveal that the early secretory pathway and MHV replication complex formation are closely connected. url: https://doi.org/10.1371/journal.ppat.1000088 doi: 10.1371/journal.ppat.1000088 id: cord-353337-o302vxqm author: Visser, Linda J. title: Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date: 2020-07-15 words: 9547.0 sentences: 514.0 pages: flesch: 54.0 cache: ./cache/cord-353337-o302vxqm.txt txt: ./txt/cord-353337-o302vxqm.txt summary: To study the effects of L pro on the induction of type I IFN in picornavirus-infected cells, we used two previously generated recombinant viruses; EMCV-L Zn , which contains inactivating mutations in the zinc-finger domain of the Leader (i.e. EMCV''s RLR signaling antagonist) [1, 43, 44] , and EMCV-L pro , which was derived from EMCV-L Zn and additionally encodes FMDV L pro at the N-terminus of its polyprotein ( Fig 1A) [45]. Cleavage of RLR signaling proteins by FMDV L pro correlates with type I IFN suppression degradation of NF-κB p65 and DUB activity as well as to impair L pro ''s ability to reduce IFN-β mRNA expression [36, 39] , also affected L pro ''s ability to cleave MAVS and TBK1. Notably, infection with EMCV L pro L143A, which displayed wt deISGylase/DUB activity but is strongly impaired in its ability to cleave/degrade RLR signaling proteins MAVS, TBK1 and NFκB p65, failed to suppress the induction of IFN-β mRNA. abstract: The type I interferon response is an important innate antiviral pathway. Recognition of viral RNA by RIG-I-like receptors (RLRs) activates a signaling cascade that leads to type I interferon (IFN-α/β) gene transcription. Multiple proteins in this signaling pathway (e.g. RIG-I, MDA5, MAVS, TBK1, IRF3) are regulated by (de)ubiquitination events. Most viruses have evolved mechanisms to counter this antiviral response. The leader protease (L(pro)) of foot-and-mouth-disease virus (FMDV) has been recognized to reduce IFN-α/β gene transcription; however, the exact mechanism is unknown. The proteolytic activity of L(pro) is vital for releasing itself from the viral polyprotein and for cleaving and degrading specific host cell proteins, such as eIF4G and NF-κB. In addition, L(pro) has been demonstrated to have deubiquitination/deISGylation activity. L(pro)’s deubiquitination/deISGylation activity and the cleavage/degradation of signaling proteins have both been postulated to be important for reduced IFN-α/β gene transcription. Here, we demonstrate that TBK1, the kinase that phosphorylates and activates the transcription factor IRF3, is cleaved by L(pro) in FMDV-infected cells as well as in cells infected with a recombinant EMCV expressing L(pro). In vitro cleavage experiments revealed that L(pro) cleaves TBK1 at residues 692–694. We also observed cleavage of MAVS in HeLa cells infected with EMCV-L(pro), but only observed decreasing levels of MAVS in FMDV-infected porcine LFPK αVβ6 cells. We set out to dissect L(pro)’s ability to cleave RLR signaling proteins from its deubiquitination/deISGylation activity to determine their relative contributions to the reduction of IFN-α/β gene transcription. The introduction of specific mutations, of which several were based on the recently published structure of L(pro) in complex with ISG15, allowed us to identify specific amino acid substitutions that separate the different proteolytic activities of L(pro). Characterization of the effects of these mutations revealed that L(pro)’s ability to cleave RLR signaling proteins but not its deubiquitination/deISGylation activity correlates with the reduced IFN-β gene transcription. url: https://www.ncbi.nlm.nih.gov/pubmed/32667958/ doi: 10.1371/journal.ppat.1008702 id: cord-001541-5d64esp4 author: Walker, Peter J. title: Evolution of Genome Size and Complexity in the Rhabdoviridae date: 2015-02-13 words: 9157.0 sentences: 398.0 pages: flesch: 45.0 cache: ./cache/cord-001541-5d64esp4.txt txt: ./txt/cord-001541-5d64esp4.txt summary: We demonstrate that remarkable changes in genome size and complexity have occurred in rhabdoviruses in a clade-specific manner, primarily by extension and insertion of additional transcriptional units in the structural protein gene junctions, followed by occasional losses. All rhabdovirus genomes contained the five canonical structural protein genes (N, P, M, G and L); however, there was remarkable diversity in the number and location of other long ORFs. Across the data set, we identified 179 additional ORFs 180 nt in length of which 142 shared no detectable protein sequence similarity with any other protein in our data set or with those in public databases (S2 Table) . Interestingly, although substantial variation in the length of gene junctions was observed in several genera (including ephemeroviruses and lyssaviruses), most variation in genome size occurred as the result of the presence of new, non-canonical ORFs in the regions between the structural protein genes (Table 1) . abstract: RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334499/ doi: 10.1371/journal.ppat.1004664 id: cord-278511-je1509ar author: Wang, David title: 5 challenges in understanding the role of the virome in health and disease date: 2020-03-26 words: 2166.0 sentences: 107.0 pages: flesch: 38.0 cache: ./cache/cord-278511-je1509ar.txt txt: ./txt/cord-278511-je1509ar.txt summary: An even more significant problem is that in most virome studies, more than 50% of the sequences in virus-enriched preparations have no detectable sequence similarity to any known reference sequences; these unalignable sequences are referred to as viral "dark matter" [8] and may include novel, highly divergent viruses that are unrecognizable. To illustrate this point, the United States National Institutes of Health (NIH) virology study sections address only "non-bacteriophage viral genetics, infection and replication, cellular and host responses to viral infections, and mechanisms of viral disease pathogenesis." Thus, there is a great need to bring these disparate communities together in order to collectively attack questions associated with the virome, especially as more complex trans-kingdom interactions are identified linking phages, bacteria, eukaryotic viruses, and eukaryotic cells. With new cell-culture systems and animal models for novel viruses, there will ideally be studies that attribute causal roles for some of the associations. abstract: nan url: https://doi.org/10.1371/journal.ppat.1008318 doi: 10.1371/journal.ppat.1008318 id: cord-328947-3l9ydspz author: Webb, L. G. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 words: 9857.0 sentences: 544.0 pages: flesch: 51.0 cache: ./cache/cord-328947-3l9ydspz.txt txt: ./txt/cord-328947-3l9ydspz.txt summary: CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . abstract: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-β transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling. url: https://doi.org/10.1371/journal.ppat.1008999 doi: 10.1371/journal.ppat.1008999 id: cord-306624-1mjmttec author: Wodrich, Harald title: A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry date: 2010-03-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/20333243/ doi: 10.1371/journal.ppat.1000808 id: cord-010762-c01wgg4v author: Wu, Jiqin title: A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase date: 2020-05-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The flaviviruses pose serious threats to human health. Being a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP), NS5 is the most conserved flavivirus protein and an important antiviral target. Previously reported NS5 structures represented by those from the Japanese encephalitis virus (JEV) and Dengue virus serotype 3 (DENV3) exhibit two apparently different global conformations, defining two sets of intra-molecular MTase-RdRP interactions. However, whether these NS5 conformations are conserved in flaviviruses and their specific functions remain elusive. Here we report two forms of DENV serotype 2 (DENV2) NS5 crystal structures representing two conformational states with defined analogies to the JEV-mode and DENV3-mode conformations, respectively, demonstrating the conservation of both conformation modes and providing clues for how different conformational states may be interconnected. Data from in vitro polymerase assays further demonstrate that perturbing the JEV-mode but not the DENV3-mode intra-molecular interactions inhibits catalysis only at initiation, while the cell-based virological analysis suggests that both modes of interactions are important for virus proliferation. Our work highlights the role of MTase as a unique intra-molecular initiation factor specifically only through the JEV-mode conformation, providing an example of conformation-based crosstalk between naturally fused protein functional modules. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219791/ doi: 10.1371/journal.ppat.1008484 id: cord-348799-qu4zin3o author: Wu, Nannan title: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation date: 2019-10-10 words: 11391.0 sentences: 520.0 pages: flesch: 48.0 cache: ./cache/cord-348799-qu4zin3o.txt txt: ./txt/cord-348799-qu4zin3o.txt summary: This lack of specificity was not present in cells however, given that the ectopic expression of ISG20 did not lead to the indiscriminate degradation of cellular RNAs (ribosomal as well as small nucleolar RNAs previously shown to be associated to ISG20 [2] ), nor of an Hepatitis C virus (HCV)-derived Luciferase reporter mRNA produced in vitro and then transfected into cells (S4C and S4D Fig) , suggesting that in cells the RNase activity of ISG20 is tightly controlled. Self mimicry allows the escape of target genes'' mRNAs from the effects of ISG20 VSV infection and ectopic DNA or RNA transfection do not bear much in common apart from the fact that both represent artificial injections into the cell of non-self genetic material from without. To further determine whether ISG20 acted on translation initiation and more specifically through specific initiation factors (eIFs), capped and polyadenylated mRNAs coding luciferase under the control of several 5'' untranslated regions (5'' UTRs) were generated in vitro and directly transfected in ISG20-expressing cells (Fig 3D) . abstract: ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation. Importantly, we demonstrate that ISG20 exerts a translational control over a large panel of non-self RNA substrates including those originating from transfected DNA, while sparing endogenous transcripts. This activity correlates with the protein’s ability to localize in cytoplasmic processing bodies. Finally, these functions are conserved in the ISG20 murine ortholog, whose genetic ablation results in mice with increased susceptibility to viral infection. Overall, our results posit ISG20 as an important defense factor able to discriminate the self/non-self origins of the RNA through translation modulation. url: https://doi.org/10.1371/journal.ppat.1008093 doi: 10.1371/journal.ppat.1008093 id: cord-331802-wo462anq author: Xia, Hongjie title: Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone date: 2015-07-28 words: 9410.0 sentences: 440.0 pages: flesch: 50.0 cache: ./cache/cord-331802-wo462anq.txt txt: ./txt/cord-331802-wo462anq.txt summary: Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. Herein, we report that although bacterially expressed EV71 2C ATPase did not exhibit any RNA remodeling activity, eukaryotically expressed EV71 2C ATPase functions not only as an RNA helicase that unwinds RNA helices from 3 0 to 5 0 in an ATP-dependent manner but also as an RNA chaperone that destabilizes helices from either direction and facilitates strand annealing and complex RNA structure formation independently of ATP. abstract: RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2C(ATPase) middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2C(ATPase) facilitated EV71 RNA synthesis in vitro; when 2C(ATPase) helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2C(ATPase)-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2C(ATPase) are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2C(ATPase), and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities. url: https://www.ncbi.nlm.nih.gov/pubmed/26218680/ doi: 10.1371/journal.ppat.1005067 id: cord-351389-48tszqh5 author: Xu, Kai title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody date: 2013-10-10 words: 6688.0 sentences: 280.0 pages: flesch: 50.0 cache: ./cache/cord-351389-48tszqh5.txt txt: ./txt/cord-351389-48tszqh5.txt summary: title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. We used X-ray crystallography to determine the high-resolution structures of the Hendra virus G glycoprotein in complex with a cross-reactive neutralizing human monoclonal antibody. Taken together, the success of hmAb m102.4 in vivo as an effective post-exposure treatment against henipavirus disease in two different well-characterized animal models (the ferret and nonhuman primate), along with the new detailed structural findings on its viral G glycoprotein binding features that help explain its superior cross-reactive neutralizing activity, will facilitate efforts aimed at obtaining approved human use application to treat accidental exposure to HeV or NiV infection. abstract: The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/24130486/ doi: 10.1371/journal.ppat.1003684 id: cord-293164-i50cgkvq author: Zhou, Bin title: Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus date: 2014-10-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses. url: https://doi.org/10.1371/journal.ppat.1004420 doi: 10.1371/journal.ppat.1004420 id: cord-001992-m4k20i7g author: Ziegler, Christopher M. title: The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles date: 2016-03-24 words: 13157.0 sentences: 580.0 pages: flesch: 53.0 cache: ./cache/cord-001992-m4k20i7g.txt txt: ./txt/cord-001992-m4k20i7g.txt summary: We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. Given the important role of the LCMV matrix protein and its late domain motif in regulating viral budding [10, 11] , we next investigated the specific effect these point mutations had on Z''s budding efficiency in a VLP release assay. To investigate the protein and genome composition of virions containing mutated late domains, an equivalent quantity of cell-free infectious virus particles from each rLCMV strain was concentrated for screening. Limiting dilutions of this UV-treated sample were applied to Vero E6 cells, followed by the addition of a fixed quantity of LCMV PFUs. As shown in Fig 5A, this allows for the determination of LCMV DI particle activity and is expressed as plaque interfering units 50 (PIU 50 ) per mL of a given sample. abstract: Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806877/ doi: 10.1371/journal.ppat.1005501 id: cord-268677-ytxrrslz author: Züst, Roland title: Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques date: 2013-08-01 words: 7936.0 sentences: 436.0 pages: flesch: 55.0 cache: ./cache/cord-268677-ytxrrslz.txt txt: ./txt/cord-268677-ytxrrslz.txt summary: Here we demonstrate that DENV strains bearing a mutation in the catalytic site of the 29-O-MTase replicated to high titres in cell culture whereas these mutant viruses were highly attenuated in mice and rhesus monkeys. Mice and monkeys infected with the mutant virus developed an immune response that fully protected them from a challenge with wild-type virus. These data suggest that vaccination with the E216A/E217A mutants does not cause ADE during heterologous challenge even though lower neutralizing Ab titers are generated by the mutant strains compared to the wild-type virus. To assess the safety (viremia profile) and efficacy (neutralizing antibody response and protection against challenge) of the 29-O-MTase mutant DENV vaccine approach in an immunologically competent host, three groups of Rhesus monkeys (RM) were immunized with different doses of E217A. These data demonstrate that live, attenuated DENV MTase mutant virus, even when administrated at low dose (1610 3 PFU), can induce protective immunity in non-human primates. abstract: Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2′-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2′-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2′-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response. url: https://doi.org/10.1371/journal.ppat.1003521 doi: 10.1371/journal.ppat.1003521 id: cord-260729-b12v3c8c author: de Lang, Anna title: Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date: 2007-08-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/17696609/ doi: 10.1371/journal.ppat.0030112 id: cord-000354-05lnj3w0 author: de Vries, Erik title: Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway date: 2011-03-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza A virus (IAV) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors. Whereas dynamin-dependent, clathrin-mediated endocytosis (CME) is generally considered as the IAV infection pathway, some observations suggest the occurrence of an as yet uncharacterized alternative entry route. By manipulating entry parameters we established experimental conditions that allow the separate analysis of dynamin-dependent and -independent entry of IAV. Whereas entry of IAV in phosphate-buffered saline could be completely inhibited by dynasore, a specific inhibitor of dynamin, a dynasore-insensitive entry pathway became functional in the presence of fetal calf serum. This finding was confirmed with the use of small interfering RNAs targeting dynamin-2. In the presence of serum, both IAV entry pathways were operational. Under these conditions entry could be fully blocked by combined treatment with dynasore and the amiloride derivative EIPA, the hallmark inhibitor of macropinocytosis, whereas either drug alone had no effect. The sensitivity of the dynamin-independent entry pathway to inhibitors or dominant-negative mutants affecting actomyosin dynamics as well as to a number of specific inhibitors of growth factor receptor tyrosine kinases and downstream effectors thereof all point to the involvement of macropinocytosis in IAV entry. Consistently, IAV particles and soluble FITC-dextran were shown to co-localize in cells in the same vesicles. Thus, in addition to the classical dynamin-dependent, clathrin-mediated endocytosis pathway, IAV enters host cells by a dynamin-independent route that has all the characteristics of macropinocytosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068995/ doi: 10.1371/journal.ppat.1001329 ==== 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