Carrel name: journal-mbio-cord Creating study carrel named journal-mbio-cord Initializing database file: cache/cord-001223-6sb3ipab.json key: cord-001223-6sb3ipab authors: Lennemann, Nicholas J.; Rhein, Bethany A.; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy title: Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1 date: 2014-01-28 journal: mBio DOI: 10.1128/mbio.00862-13 sha: doc_id: 1223 cord_uid: 6sb3ipab file: cache/cord-001340-kqcx7lrq.json key: cord-001340-kqcx7lrq authors: Ladner, Jason T.; Beitzel, Brett; Chain, Patrick S. G.; Davenport, Matthew G.; Donaldson, Eric; Frieman, Matthew; Kugelman, Jeffrey; Kuhn, Jens H.; O’Rear, Jules; Sabeti, Pardis C.; Wentworth, David E.; Wiley, Michael R.; Yu, Guo-Yun; Sozhamannan, Shanmuga; Bradburne, Christopher; Palacios, Gustavo title: Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing date: 2014-06-17 journal: mBio DOI: 10.1128/mbio.01360-14 sha: doc_id: 1340 cord_uid: kqcx7lrq file: cache/cord-256970-b8czrq29.json key: cord-256970-b8czrq29 authors: Ielasi, Francesco S.; Alioscha-Perez, Mitchel; Donohue, Dagmara; Claes, Sandra; Sahli, Hichem; Schols, Dominique; Willaert, Ronnie G. title: Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins date: 2016-07-12 journal: mBio DOI: 10.1128/mbio.00584-16 sha: doc_id: 256970 cord_uid: b8czrq29 file: cache/cord-263357-krvei97r.json key: cord-263357-krvei97r authors: Holmes, Kathryn V.; Dominguez, Samuel R. title: The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia date: 2013-01-08 journal: mBio DOI: 10.1128/mbio.00548-12 sha: doc_id: 263357 cord_uid: krvei97r file: cache/cord-001152-v6uc0ijw.json key: cord-001152-v6uc0ijw authors: Girardi, Erika; Chane-Woon-Ming, Béatrice; Messmer, Mélanie; Kaukinen, Pasi; Pfeffer, Sébastien title: Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells date: 2013-11-19 journal: mBio DOI: 10.1128/mbio.00698-13 sha: doc_id: 1152 cord_uid: v6uc0ijw file: cache/cord-003092-3owcqt3d.json key: cord-003092-3owcqt3d authors: Iketani, Sho; Shean, Ryan C.; Ferren, Marion; Makhsous, Negar; Aquino, Dolly B.; des Georges, Amedee; Rima, Bert; Mathieu, Cyrille; Porotto, Matteo; Moscona, Anne; Greninger, Alexander L. title: Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation date: 2018-07-03 journal: mBio DOI: 10.1128/mbio.00898-18 sha: doc_id: 3092 cord_uid: 3owcqt3d file: cache/cord-001450-7vsdqhi0.json key: cord-001450-7vsdqhi0 authors: Burgess, Stacey L.; Buonomo, Erica; Carey, Maureen; Cowardin, Carrie; Naylor, Caitlin; Noor, Zannatun; Wills-Karp, Marsha; Petri, William A. title: Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis date: 2014-11-04 journal: mBio DOI: 10.1128/mbio.01817-14 sha: doc_id: 1450 cord_uid: 7vsdqhi0 file: cache/cord-003609-p0ydzjre.json key: cord-003609-p0ydzjre authors: Goodman, Danielle E.; Pretto, Carla D.; Krepostman, Tomas A.; Carnahan, Kelly E.; Spindler, Katherine R. title: Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date: 2019-04-23 journal: mBio DOI: 10.1128/mbio.00668-19 sha: doc_id: 3609 cord_uid: p0ydzjre file: cache/cord-001527-x8yswoua.json key: cord-001527-x8yswoua authors: Lipsitch, Marc; Inglesby, Thomas V. title: Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited” date: 2015-01-23 journal: mBio DOI: 10.1128/mbio.00041-15 sha: doc_id: 1527 cord_uid: x8yswoua file: cache/cord-260087-9o9tb28h.json key: cord-260087-9o9tb28h authors: Furmanski, Martin title: The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards date: 2015-09-29 journal: mBio DOI: 10.1128/mbio.01434-15 sha: doc_id: 260087 cord_uid: 9o9tb28h file: cache/cord-003143-n6b0r92e.json key: cord-003143-n6b0r92e authors: Zhao, Min; Liu, Kefang; Luo, Jiejian; Tan, Shuguang; Quan, Chuansong; Zhang, Shuijun; Chai, Yan; Qi, Jianxun; Li, Yan; Bi, Yuhai; Xiao, Haixia; Wong, Gary; Zhou, Jianfang; Jiang, Taijiao; Liu, Wenjun; Yu, Hongjie; Yan, Jinghua; Liu, Yingxia; Shu, Yuelong; Wu, Guizhen; Wu, Aiping; Gao, George F.; Liu, William J. title: Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses date: 2018-08-07 journal: mBio DOI: 10.1128/mbio.01408-18 sha: doc_id: 3143 cord_uid: n6b0r92e file: cache/cord-292883-7hvq9qaj.json key: cord-292883-7hvq9qaj authors: Nguyen-Contant, Phuong; Embong, A. Karim; Kanagaiah, Preshetha; Chaves, Francisco A.; Yang, Hongmei; Branche, Angela R.; Topham, David J.; Sangster, Mark Y. title: S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit date: 2020-09-25 journal: mBio DOI: 10.1128/mbio.01991-20 sha: doc_id: 292883 cord_uid: 7hvq9qaj file: cache/cord-274396-l611eisi.json key: cord-274396-l611eisi authors: Park, Su-Jin; Yu, Kwang-Min; Kim, Young-Il; Kim, Se-Mi; Kim, Eun-Ha; Kim, Seong-Gyu; Kim, Eun Ji; Casel, Mark Anthony B.; Rollon, Rare; Jang, Seung-Gyu; Lee, Min-Hyeok; Chang, Jae-Hyung; Song, Min-Suk; Jeong, Hye Won; Choi, Younho; Chen, Weiqiang; Shin, Woo-Jin; Jung, Jae U.; Choi, Young Ki title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date: 2020-05-22 journal: mBio DOI: 10.1128/mbio.01114-20 sha: doc_id: 274396 cord_uid: l611eisi file: cache/cord-004469-m2fwefuy.json key: cord-004469-m2fwefuy authors: Rivera-Hernandez, Tania; Rhyme, Mira Syahira; Cork, Amanda J.; Jones, Scott; Segui-Perez, Celia; Brunner, Livia; Richter, Johanna; Petrovsky, Nikolai; Lawrenz, Maria; Goldblatt, David; Collin, Nicolas; Walker, Mark J. title: Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies date: 2020-03-10 journal: mBio DOI: 10.1128/mbio.00122-20 sha: doc_id: 4469 cord_uid: m2fwefuy file: cache/cord-252671-uf96jgig.json key: cord-252671-uf96jgig authors: Wang, Yi; Liu, Li title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism date: 2016-02-09 journal: mBio DOI: 10.1128/mbio.01872-15 sha: doc_id: 252671 cord_uid: uf96jgig file: cache/cord-298773-vnmc6nqd.json key: cord-298773-vnmc6nqd authors: Pfeiffer, Julie K. title: Is the Debate and “Pause” on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? date: 2015-01-20 journal: mBio DOI: 10.1128/mbio.02525-14 sha: doc_id: 298773 cord_uid: vnmc6nqd file: cache/cord-012487-s920s5wb.json key: cord-012487-s920s5wb authors: Noga, Marek J.; Büke, Ferhat; van den Broek, Niels J. F.; Imholz, Nicole C. E.; Scherer, Nicole; Yang, Flora; Bokinsky, Gregory title: Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date: 2020-08-18 journal: mBio DOI: 10.1128/mbio.02703-19 sha: doc_id: 12487 cord_uid: s920s5wb file: cache/cord-286587-x0wqtlxh.json key: cord-286587-x0wqtlxh authors: Fedson, David S.; Opal, Steven M.; Rordam, Ole Martin title: Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection date: 2020-03-20 journal: mBio DOI: 10.1128/mbio.00398-20 sha: doc_id: 286587 cord_uid: x0wqtlxh file: cache/cord-001528-33f94doo.json key: cord-001528-33f94doo authors: Fouchier, Ron A. M. title: Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited date: 2015-01-23 journal: mBio DOI: 10.1128/mbio.02560-14 sha: doc_id: 1528 cord_uid: 33f94doo file: cache/cord-287487-qeltdch7.json key: cord-287487-qeltdch7 authors: Graepel, Kevin W.; Lu, Xiaotao; Case, James Brett; Sexton, Nicole R.; Smith, Everett Clinton; Denison, Mark R. title: Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations date: 2017-11-07 journal: mBio DOI: 10.1128/mbio.01503-17 sha: doc_id: 287487 cord_uid: qeltdch7 file: cache/cord-297082-2rhoffx2.json key: cord-297082-2rhoffx2 authors: Yu, Changqing; Li, Sunan; Zhang, Xianfeng; Khan, Ilyas; Ahmad, Iqbal; Zhou, Yulong; Li, Shuo; Shi, Jing; Wang, Yu; Zheng, Yong-Hui title: MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date: 2020-09-15 journal: mBio DOI: 10.1128/mbio.01882-20 sha: doc_id: 297082 cord_uid: 2rhoffx2 file: cache/cord-305698-fjd0rsrf.json key: cord-305698-fjd0rsrf authors: Imperiale, Michael J.; Casadevall, Arturo title: Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus date: 2014-12-12 journal: mBio DOI: 10.1128/mbio.02292-14 sha: doc_id: 305698 cord_uid: fjd0rsrf file: cache/cord-327660-p1b07b4t.json key: cord-327660-p1b07b4t authors: Wolf, Yuri I.; Kazlauskas, Darius; Iranzo, Jaime; Lucía-Sanz, Adriana; Kuhn, Jens H.; Krupovic, Mart; Dolja, Valerian V.; Koonin, Eugene V. title: Origins and Evolution of the Global RNA Virome date: 2018-11-27 journal: mBio DOI: 10.1128/mbio.02329-18 sha: doc_id: 327660 cord_uid: p1b07b4t file: cache/cord-278303-lnrgom58.json key: cord-278303-lnrgom58 authors: Björnsdóttir, Sigríður; Harris, Simon R.; Svansson, Vilhjálmur; Gunnarsson, Eggert; Sigurðardóttir, Ólöf G.; Gammeljord, Kristina; Steward, Karen F.; Newton, J. Richard; Robinson, Carl; Charbonneau, Amelia R. L.; Parkhill, Julian; Holden, Matthew T. G.; Waller, Andrew S. title: Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases date: 2017-08-01 journal: mBio DOI: 10.1128/mbio.00826-17 sha: doc_id: 278303 cord_uid: lnrgom58 file: cache/cord-281389-sht0yx4a.json key: cord-281389-sht0yx4a authors: Tal, Michal Caspi; Torrez Dulgeroff, Laughing Bear; Myers, Lara; Cham, Lamin B.; Mayer-Barber, Katrin D.; Bohrer, Andrea C.; Castro, Ehydel; Yiu, Ying Ying; Lopez Angel, Cesar; Pham, Ed; Carmody, Aaron B.; Messer, Ronald J.; Gars, Eric; Kortmann, Jens; Markovic, Maxim; Hasenkrug, Michaela; Peterson, Karin E.; Winkler, Clayton W.; Woods, Tyson A.; Hansen, Paige; Galloway, Sarah; Wagh, Dhananjay; Fram, Benjamin J.; Nguyen, Thai; Corey, Daniel; Kalluru, Raja Sab; Banaei, Niaz; Rajadas, Jayakumar; Monack, Denise M.; Ahmed, Aijaz; Sahoo, Debashis; Davis, Mark M.; Glenn, Jeffrey S.; Adomati, Tom; Lang, Karl S.; Weissman, Irving L.; Hasenkrug, Kim J. title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date: 2020-06-23 journal: mBio DOI: 10.1128/mbio.01293-20 sha: doc_id: 281389 cord_uid: sht0yx4a file: cache/cord-001672-7lh8iqm1.json key: cord-001672-7lh8iqm1 authors: Klotz, Lynn C. title: Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory date: 2015-04-14 journal: mBio DOI: 10.1128/mbio.00268-15 sha: doc_id: 1672 cord_uid: 7lh8iqm1 file: cache/cord-279979-3ecnbqom.json key: cord-279979-3ecnbqom authors: Anthony, S. J.; Gilardi, K.; Menachery, V. D.; Goldstein, T.; Ssebide, B.; Mbabazi, R.; Navarrete-Macias, I.; Liang, E.; Wells, H.; Hicks, A.; Petrosov, A.; Byarugaba, D. K.; Debbink, K.; Dinnon, K. H.; Scobey, T.; Randell, S. H.; Yount, B. L.; Cranfield, M.; Johnson, C. K.; Baric, R. S.; Lipkin, W. I.; Mazet, J. A. K. title: Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus date: 2017-04-04 journal: mBio DOI: 10.1128/mbio.00373-17 sha: doc_id: 279979 cord_uid: 3ecnbqom file: cache/cord-002467-b0p1b4g8.json key: cord-002467-b0p1b4g8 authors: Leyva-Grado, Victor H.; Ermler, Megan E.; Schotsaert, Michael; Gonzalez, Ma G.; Gillespie, Virginia; Lim, Jean K.; García-Sastre, Adolfo title: Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection date: 2017-03-28 journal: mBio DOI: 10.1128/mbio.00229-17 sha: doc_id: 2467 cord_uid: b0p1b4g8 file: cache/cord-326160-mf0vh6iu.json key: cord-326160-mf0vh6iu authors: de Wit, Emmie; Rasmussen, Angela L.; Feldmann, Friederike; Bushmaker, Trenton; Martellaro, Cynthia; Haddock, Elaine; Okumura, Atsushi; Proll, Sean C.; Chang, Jean; Gardner, Don; Katze, Michael G.; Munster, Vincent J.; Feldmann, Heinz title: Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques date: 2014-08-12 journal: mBio DOI: 10.1128/mbio.01331-14 sha: doc_id: 326160 cord_uid: mf0vh6iu file: cache/cord-303915-14yfs4pa.json key: cord-303915-14yfs4pa authors: Almazán, Fernando; DeDiego, Marta L.; Sola, Isabel; Zuñiga, Sonia; Nieto-Torres, Jose L.; Marquez-Jurado, Silvia; Andrés, German; Enjuanes, Luis title: Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate date: 2013-09-10 journal: mBio DOI: 10.1128/mbio.00650-13 sha: doc_id: 303915 cord_uid: 14yfs4pa file: cache/cord-296028-hqrd1e8p.json key: cord-296028-hqrd1e8p authors: Rozell, Daniel J. title: Assessing and Managing the Risks of Potential Pandemic Pathogen Research date: 2015-07-21 journal: mBio DOI: 10.1128/mbio.01075-15 sha: doc_id: 296028 cord_uid: hqrd1e8p file: cache/cord-335432-9aszklx3.json key: cord-335432-9aszklx3 authors: Duprex, W. Paul; Casadevall, Arturo title: Falling down the Rabbit Hole: aTRIP Toward Lexiconic Precision in the “Gain-of-Function” Debate date: 2014-12-12 journal: mBio DOI: 10.1128/mbio.02421-14 sha: doc_id: 335432 cord_uid: 9aszklx3 file: cache/cord-337492-o6sy4zi4.json key: cord-337492-o6sy4zi4 authors: Baric, Ralph S.; Crosson, Sean; Damania, Blossom; Miller, Samuel I.; Rubin, Eric J. title: Next-Generation High-Throughput Functional Annotation of Microbial Genomes date: 2016-10-04 journal: mBio DOI: 10.1128/mbio.01245-16 sha: doc_id: 337492 cord_uid: o6sy4zi4 file: cache/cord-256550-72i1x02f.json key: cord-256550-72i1x02f authors: Klotz, Lynn C. title: Danger of Potential-Pandemic-Pathogen Research Enterprises date: 2015-06-16 journal: mBio DOI: 10.1128/mbio.00815-15 sha: doc_id: 256550 cord_uid: 72i1x02f file: cache/cord-330315-upcf15q5.json key: cord-330315-upcf15q5 authors: Oudshoorn, Diede; Rijs, Kevin; Limpens, Ronald W. A. L.; Groen, Kevin; Koster, Abraham J.; Snijder, Eric J.; Kikkert, Marjolein; Bárcena, Montserrat title: Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication date: 2017-11-21 journal: mBio DOI: 10.1128/mbio.01658-17 sha: doc_id: 330315 cord_uid: upcf15q5 file: cache/cord-353612-9ux181xg.json key: cord-353612-9ux181xg authors: Josset, Laurence; Menachery, Vineet D.; Gralinski, Lisa E.; Agnihothram, Sudhakar; Sova, Pavel; Carter, Victoria S.; Yount, Boyd L.; Graham, Rachel L.; Baric, Ralph S.; Katze, Michael G. title: Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus date: 2013-04-30 journal: mBio DOI: 10.1128/mbio.00165-13 sha: doc_id: 353612 cord_uid: 9ux181xg file: cache/cord-334463-nvu5tqxb.json key: cord-334463-nvu5tqxb authors: Kim, Chonsaeng; Bergelson, Jeffrey M. title: Echovirus 7 Entry into Polarized Intestinal Epithelial Cells Requires Clathrin and Rab7 date: 2012-04-10 journal: mBio DOI: 10.1128/mbio.00304-11 sha: doc_id: 334463 cord_uid: nvu5tqxb file: cache/cord-274663-zyzgk2z3.json key: cord-274663-zyzgk2z3 authors: Chang, Stewart T.; Sova, Pavel; Peng, Xinxia; Weiss, Jeffrey; Law, G. Lynn; Palermo, Robert E.; Katze, Michael G. title: Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line date: 2011-09-20 journal: mBio DOI: 10.1128/mbio.00134-11 sha: doc_id: 274663 cord_uid: zyzgk2z3 file: cache/cord-308848-chvvtr0d.json key: cord-308848-chvvtr0d authors: Fidel, Paul L.; Noverr, Mairi C. title: Reply to Özdemir, “Measles-Mumps-Rubella Vaccine and COVID-19 Relationship” date: 2020-09-22 journal: mBio DOI: 10.1128/mbio.02465-20 sha: doc_id: 308848 cord_uid: chvvtr0d file: cache/cord-287892-bnqmwst8.json key: cord-287892-bnqmwst8 authors: Hyser, Joseph M.; Collinson-Pautz, Matthew R.; Utama, Budi; Estes, Mary K. title: Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity date: 2010-11-30 journal: mBio DOI: 10.1128/mbio.00265-10 sha: doc_id: 287892 cord_uid: bnqmwst8 file: cache/cord-303262-grrd6jmt.json key: cord-303262-grrd6jmt authors: Tournier, Jean-Nicolas title: Pandemic Legion History More Complex than Previously Thought date: 2020-10-09 journal: mBio DOI: 10.1128/mbio.02377-20 sha: doc_id: 303262 cord_uid: grrd6jmt file: cache/cord-289360-h6wvx7gw.json key: cord-289360-h6wvx7gw authors: Imperiale, Michael J.; Casadevall, Arturo title: The Importance of Virology at a Time of Great Need and Great Jeopardy date: 2015-03-10 journal: mBio DOI: 10.1128/mbio.00236-15 sha: doc_id: 289360 cord_uid: h6wvx7gw file: cache/cord-344227-rdlinzrn.json key: cord-344227-rdlinzrn authors: Gralinski, Lisa E.; Sheahan, Timothy P.; Morrison, Thomas E.; Menachery, Vineet D.; Jensen, Kara; Leist, Sarah R.; Whitmore, Alan; Heise, Mark T.; Baric, Ralph S. title: Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis date: 2018-10-09 journal: mBio DOI: 10.1128/mbio.01753-18 sha: doc_id: 344227 cord_uid: rdlinzrn file: cache/cord-348669-mizygp4j.json key: cord-348669-mizygp4j authors: Beall, Anne; Yount, Boyd; Lin, Chun-Ming; Hou, Yixuan; Wang, Qiuhong; Saif, Linda; Baric, Ralph title: Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A date: 2016-01-05 journal: mBio DOI: 10.1128/mbio.01451-15 sha: doc_id: 348669 cord_uid: mizygp4j file: cache/cord-264050-6zpw6itb.json key: cord-264050-6zpw6itb authors: Pirofski, Liise-anne; Casadevall, Arturo title: Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response date: 2017-12-12 journal: mBio DOI: 10.1128/mbio.02063-17 sha: doc_id: 264050 cord_uid: 6zpw6itb file: cache/cord-280001-y7pvj2l1.json key: cord-280001-y7pvj2l1 authors: Patel, Robin; Babady, Esther; Theel, Elitza S.; Storch, Gregory A.; Pinsky, Benjamin A.; St. George, Kirsten; Smith, Tara C.; Bertuzzi, Stefano title: Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19 date: 2020-03-26 journal: mBio DOI: 10.1128/mbio.00722-20 sha: doc_id: 280001 cord_uid: y7pvj2l1 file: cache/cord-331361-pd9lt4n2.json key: cord-331361-pd9lt4n2 authors: Mathieu, Cyrille; Dhondt, Kévin P.; Châlons, Marie; Mély, Stéphane; Raoul, Hervé; Negre, Didier; Cosset, François-Loïc; Gerlier, Denis; Vivès, Romain R.; Horvat, Branka title: Heparan Sulfate-Dependent Enhancement of Henipavirus Infection date: 2015-03-10 journal: mBio DOI: 10.1128/mbio.02427-14 sha: doc_id: 331361 cord_uid: pd9lt4n2 file: cache/cord-348131-pkovyjo6.json key: cord-348131-pkovyjo6 authors: Li, Yize; Dong, Beihua; Wei, Zuzhang; Silverman, Robert H.; Weiss, Susan R. title: Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling date: 2019-11-12 journal: mBio DOI: 10.1128/mbio.02414-19 sha: doc_id: 348131 cord_uid: pkovyjo6 file: cache/cord-273391-vmtfn78x.json key: cord-273391-vmtfn78x authors: Li, Kun; Li, Zhuo; Wohlford-Lenane, Christine; Meyerholz, David K.; Channappanavar, Rudragouda; An, Dong; Perlman, Stanley; McCray, Paul B.; He, Biao title: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection date: 2020-04-07 journal: mBio DOI: 10.1128/mbio.00554-20 sha: doc_id: 273391 cord_uid: vmtfn78x file: cache/cord-341858-uz7vqq3r.json key: cord-341858-uz7vqq3r authors: Davis, C. Todd; Chen, Li-Mei; Pappas, Claudia; Stevens, James; Tumpey, Terrence M.; Gubareva, Larisa V.; Katz, Jacqueline M.; Villanueva, Julie M.; Donis, Ruben O.; Cox, Nancy J. title: Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness date: 2014-12-12 journal: mBio DOI: 10.1128/mbio.02431-14 sha: doc_id: 341858 cord_uid: uz7vqq3r file: cache/cord-290297-efo9f7c5.json key: cord-290297-efo9f7c5 authors: Vaillancourt, Mylene; Jorth, Peter title: The Unrecognized Threat of Secondary Bacterial Infections with COVID-19 date: 2020-08-07 journal: mBio DOI: 10.1128/mbio.01806-20 sha: doc_id: 290297 cord_uid: efo9f7c5 file: cache/cord-305336-wxiazglk.json key: cord-305336-wxiazglk authors: Li, Ji Lian; Cornman, R. Scott; Evans, Jay D.; Pettis, Jeffery S.; Zhao, Yan; Murphy, Charles; Peng, Wen Jun; Wu, Jie; Hamilton, Michele; Boncristiani, Humberto F.; Zhou, Liang; Hammond, John; Chen, Yan Ping title: Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera date: 2014-01-21 journal: mBio DOI: 10.1128/mbio.00898-13 sha: doc_id: 305336 cord_uid: wxiazglk file: cache/cord-274399-cd7cmpoj.json key: cord-274399-cd7cmpoj authors: Barzin, Amir; Schmitz, John L.; Rosin, Samuel; Sirpal, Rameet; Almond, Martha; Robinette, Carole; Wells, Samantha; Hudgens, Michael; Olshan, Andrew; Deen, Stephanie; Krejci, Patrick; Quackenbush, Eugenia; Chronowski, Kevin; Cornaby, Caleb; Goins, Janette; Butler, Linda; Aucoin, Julia; Boyer, Kim; Faulk, Janet; Alston-Johnson, Devena; Page, Cristen; Zhou, Yijun; Fiscus, Lynne; Damania, Blossom; Dittmer, Dirk P.; Peden, David B. title: SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date: 2020-09-29 journal: mBio DOI: 10.1128/mbio.02426-20 sha: doc_id: 274399 cord_uid: cd7cmpoj file: cache/cord-356325-gk5jve0i.json key: cord-356325-gk5jve0i authors: Beaudoin-Bussières, Guillaume; Laumaea, Annemarie; Anand, Sai Priya; Prévost, Jérémie; Gasser, Romain; Goyette, Guillaume; Medjahed, Halima; Perreault, Josée; Tremblay, Tony; Lewin, Antoine; Gokool, Laurie; Morrisseau, Chantal; Bégin, Philippe; Tremblay, Cécile; Martel-Laferrière, Valérie; Kaufmann, Daniel E.; Richard, Jonathan; Bazin, Renée; Finzi, Andrés title: Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals date: 2020-10-16 journal: mBio DOI: 10.1128/mbio.02590-20 sha: doc_id: 356325 cord_uid: gk5jve0i file: cache/cord-324978-9qfhsj3n.json key: cord-324978-9qfhsj3n authors: Alagaili, Abdulaziz N.; Briese, Thomas; Mishra, Nischay; Kapoor, Vishal; Sameroff, Stephen C.; de Wit, Emmie; Munster, Vincent J.; Hensley, Lisa E.; Zalmout, Iyad S.; Kapoor, Amit; Epstein, Jonathan H.; Karesh, William B.; Daszak, Peter; Mohammed, Osama B.; Lipkin, W. Ian title: Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date: 2014-02-25 journal: mBio DOI: 10.1128/mbio.00884-14 sha: doc_id: 324978 cord_uid: 9qfhsj3n file: cache/cord-335938-hscgmis5.json key: cord-335938-hscgmis5 authors: Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S. title: Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury date: 2013-08-06 journal: mBio DOI: 10.1128/mbio.00271-13 sha: doc_id: 335938 cord_uid: hscgmis5 file: cache/cord-351482-hzh5tyoo.json key: cord-351482-hzh5tyoo authors: Peng, Xinxia; Gralinski, Lisa; Ferris, Martin T.; Frieman, Matthew B.; Thomas, Matthew J.; Proll, Sean; Korth, Marcus J.; Tisoncik, Jennifer R.; Heise, Mark; Luo, Shujun; Schroth, Gary P.; Tumpey, Terrence M.; Li, Chengjun; Kawaoka, Yoshihiro; Baric, Ralph S.; Katze, Michael G. title: Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection date: 2011-11-15 journal: mBio DOI: 10.1128/mbio.00198-11 sha: doc_id: 351482 cord_uid: hzh5tyoo file: cache/cord-295946-p9enjxiq.json key: cord-295946-p9enjxiq authors: Hattori, Shin-ichiro; Higshi-Kuwata, Nobuyo; Raghavaiah, Jakka; Das, Debananda; Bulut, Haydar; Davis, David A.; Takamatsu, Yuki; Matsuda, Kouki; Takamune, Nobutoki; Kishimoto, Naoki; Okamura, Tadashi; Misumi, Shogo; Yarchoan, Robert; Maeda, Kenji; Ghosh, Arun K.; Mitsuya, Hiroaki title: GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection date: 2020-08-20 journal: mBio DOI: 10.1128/mbio.01833-20 sha: doc_id: 295946 cord_uid: p9enjxiq file: cache/cord-292742-mio4przi.json key: cord-292742-mio4przi authors: McAloose, Denise; Laverack, Melissa; Wang, Leyi; Killian, Mary Lea; Caserta, Leonardo C.; Yuan, Fangfeng; Mitchell, Patrick K.; Queen, Krista; Mauldin, Matthew R.; Cronk, Brittany D.; Bartlett, Susan L.; Sykes, John M.; Zec, Stephanie; Stokol, Tracy; Ingerman, Karen; Delaney, Martha A.; Fredrickson, Richard; Ivančić, Marina; Jenkins-Moore, Melinda; Mozingo, Katie; Franzen, Kerrie; Bergeson, Nichole Hines; Goodman, Laura; Wang, Haibin; Fang, Ying; Olmstead, Colleen; McCann, Colleen; Thomas, Patrick; Goodrich, Erin; Elvinger, François; Smith, David C.; Tong, Suxiang; Slavinski, Sally; Calle, Paul P.; Terio, Karen; Torchetti, Mia Kim; Diel, Diego G. title: From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date: 2020-10-13 journal: mBio DOI: 10.1128/mbio.02220-20 sha: doc_id: 292742 cord_uid: mio4przi file: cache/cord-350603-ssen3q08.json key: cord-350603-ssen3q08 authors: Albrecht, Randy A.; Liu, Wen-Chun; Sant, Andrea J.; Tompkins, S. Mark; Pekosz, Andrew; Meliopoulos, Victoria; Cherry, Sean; Thomas, Paul G.; Schultz-Cherry, Stacey title: Moving Forward: Recent Developments for the Ferret Biomedical Research Model date: 2018-07-17 journal: mBio DOI: 10.1128/mbio.01113-18 sha: doc_id: 350603 cord_uid: ssen3q08 file: cache/cord-339269-7m53i1h9.json key: cord-339269-7m53i1h9 authors: Pope, Welkin H.; Jacobs-Sera, Deborah; Russell, Daniel A.; Rubin, Daniel H. F.; Kajee, Afsana; Msibi, Zama N. P.; Larsen, Michelle H.; Jacobs, William R.; Lawrence, Jeffrey G.; Hendrix, Roger W.; Hatfull, Graham F. title: Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood date: 2014-12-02 journal: mBio DOI: 10.1128/mbio.02145-14 sha: doc_id: 339269 cord_uid: 7m53i1h9 file: cache/cord-352096-cc3dzycl.json key: cord-352096-cc3dzycl authors: Richman, Douglas D. title: Antiviral Drug Discovery To Address the COVID-19 Pandemic date: 2020-09-25 journal: mBio DOI: 10.1128/mbio.02134-20 sha: doc_id: 352096 cord_uid: cc3dzycl Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-mbio-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: 64118 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-286587-x0wqtlxh author: Fedson, David S. title: Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection date: 2020-03-20 pages: extension: .txt txt: ./txt/cord-286587-x0wqtlxh.txt cache: ./cache/cord-286587-x0wqtlxh.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 1 resourceName b'cord-286587-x0wqtlxh.txt' === file2bib.sh === id: cord-260087-9o9tb28h author: Furmanski, Martin title: The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards date: 2015-09-29 pages: extension: .txt txt: ./txt/cord-260087-9o9tb28h.txt cache: ./cache/cord-260087-9o9tb28h.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-260087-9o9tb28h.txt' === file2bib.sh === id: cord-289360-h6wvx7gw author: Imperiale, Michael J. title: The Importance of Virology at a Time of Great Need and Great Jeopardy date: 2015-03-10 pages: extension: .txt txt: ./txt/cord-289360-h6wvx7gw.txt cache: ./cache/cord-289360-h6wvx7gw.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-289360-h6wvx7gw.txt' === file2bib.sh === id: cord-308848-chvvtr0d author: Fidel, Paul L. title: Reply to Özdemir, “Measles-Mumps-Rubella Vaccine and COVID-19 Relationship” date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-308848-chvvtr0d.txt cache: ./cache/cord-308848-chvvtr0d.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-308848-chvvtr0d.txt' === file2bib.sh === id: cord-350603-ssen3q08 author: Albrecht, Randy A. title: Moving Forward: Recent Developments for the Ferret Biomedical Research Model date: 2018-07-17 pages: extension: .txt txt: ./txt/cord-350603-ssen3q08.txt cache: ./cache/cord-350603-ssen3q08.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-350603-ssen3q08.txt' === file2bib.sh === id: cord-280001-y7pvj2l1 author: Patel, Robin title: Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19 date: 2020-03-26 pages: extension: .txt txt: ./txt/cord-280001-y7pvj2l1.txt cache: ./cache/cord-280001-y7pvj2l1.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-280001-y7pvj2l1.txt' === file2bib.sh === id: cord-303262-grrd6jmt author: Tournier, Jean-Nicolas title: Pandemic Legion History More Complex than Previously Thought date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-303262-grrd6jmt.txt cache: ./cache/cord-303262-grrd6jmt.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 1 resourceName b'cord-303262-grrd6jmt.txt' === file2bib.sh === id: cord-290297-efo9f7c5 author: Vaillancourt, Mylene title: The Unrecognized Threat of Secondary Bacterial Infections with COVID-19 date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-290297-efo9f7c5.txt cache: ./cache/cord-290297-efo9f7c5.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-290297-efo9f7c5.txt' === file2bib.sh === id: cord-296028-hqrd1e8p author: Rozell, Daniel J. title: Assessing and Managing the Risks of Potential Pandemic Pathogen Research date: 2015-07-21 pages: extension: .txt txt: ./txt/cord-296028-hqrd1e8p.txt cache: ./cache/cord-296028-hqrd1e8p.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-296028-hqrd1e8p.txt' === file2bib.sh === id: cord-356325-gk5jve0i author: Beaudoin-Bussières, Guillaume title: Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-356325-gk5jve0i.txt cache: ./cache/cord-356325-gk5jve0i.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-356325-gk5jve0i.txt' === file2bib.sh === id: cord-298773-vnmc6nqd author: Pfeiffer, Julie K. title: Is the Debate and “Pause” on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? date: 2015-01-20 pages: extension: .txt txt: ./txt/cord-298773-vnmc6nqd.txt cache: ./cache/cord-298773-vnmc6nqd.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 1 resourceName b'cord-298773-vnmc6nqd.txt' === file2bib.sh === id: cord-352096-cc3dzycl author: Richman, Douglas D. title: Antiviral Drug Discovery To Address the COVID-19 Pandemic date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-352096-cc3dzycl.txt cache: ./cache/cord-352096-cc3dzycl.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-352096-cc3dzycl.txt' === file2bib.sh === id: cord-263357-krvei97r author: Holmes, Kathryn V. title: The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia date: 2013-01-08 pages: extension: .txt txt: ./txt/cord-263357-krvei97r.txt cache: ./cache/cord-263357-krvei97r.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-263357-krvei97r.txt' === file2bib.sh === id: cord-305698-fjd0rsrf author: Imperiale, Michael J. title: Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus date: 2014-12-12 pages: extension: .txt txt: ./txt/cord-305698-fjd0rsrf.txt cache: ./cache/cord-305698-fjd0rsrf.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-305698-fjd0rsrf.txt' === file2bib.sh === id: cord-335432-9aszklx3 author: Duprex, W. Paul title: Falling down the Rabbit Hole: aTRIP Toward Lexiconic Precision in the “Gain-of-Function” Debate date: 2014-12-12 pages: extension: .txt txt: ./txt/cord-335432-9aszklx3.txt cache: ./cache/cord-335432-9aszklx3.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-335432-9aszklx3.txt' === file2bib.sh === id: cord-001340-kqcx7lrq author: Ladner, Jason T. title: Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing date: 2014-06-17 pages: extension: .txt txt: ./txt/cord-001340-kqcx7lrq.txt cache: ./cache/cord-001340-kqcx7lrq.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-001340-kqcx7lrq.txt' === file2bib.sh === id: cord-001528-33f94doo author: Fouchier, Ron A. M. title: Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited date: 2015-01-23 pages: extension: .txt txt: ./txt/cord-001528-33f94doo.txt cache: ./cache/cord-001528-33f94doo.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 1 resourceName b'cord-001528-33f94doo.txt' === file2bib.sh === id: cord-001672-7lh8iqm1 author: Klotz, Lynn C. title: Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory date: 2015-04-14 pages: extension: .txt txt: ./txt/cord-001672-7lh8iqm1.txt cache: ./cache/cord-001672-7lh8iqm1.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-001672-7lh8iqm1.txt' === file2bib.sh === id: cord-337492-o6sy4zi4 author: Baric, Ralph S. title: Next-Generation High-Throughput Functional Annotation of Microbial Genomes date: 2016-10-04 pages: extension: .txt txt: ./txt/cord-337492-o6sy4zi4.txt cache: ./cache/cord-337492-o6sy4zi4.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-337492-o6sy4zi4.txt' === file2bib.sh === id: cord-264050-6zpw6itb author: Pirofski, Liise-anne title: Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response date: 2017-12-12 pages: extension: .txt txt: ./txt/cord-264050-6zpw6itb.txt cache: ./cache/cord-264050-6zpw6itb.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-264050-6zpw6itb.txt' === file2bib.sh === id: cord-324978-9qfhsj3n author: Alagaili, Abdulaziz N. title: Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date: 2014-02-25 pages: extension: .txt txt: ./txt/cord-324978-9qfhsj3n.txt cache: ./cache/cord-324978-9qfhsj3n.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-324978-9qfhsj3n.txt' === file2bib.sh === id: cord-001450-7vsdqhi0 author: Burgess, Stacey L. title: Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis date: 2014-11-04 pages: extension: .txt txt: ./txt/cord-001450-7vsdqhi0.txt cache: ./cache/cord-001450-7vsdqhi0.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-001450-7vsdqhi0.txt' === file2bib.sh === id: cord-292883-7hvq9qaj author: Nguyen-Contant, Phuong title: S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-292883-7hvq9qaj.txt cache: ./cache/cord-292883-7hvq9qaj.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-292883-7hvq9qaj.txt' === file2bib.sh === id: cord-274399-cd7cmpoj author: Barzin, Amir title: SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-274399-cd7cmpoj.txt cache: ./cache/cord-274399-cd7cmpoj.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-274399-cd7cmpoj.txt' === file2bib.sh === id: cord-001527-x8yswoua author: Lipsitch, Marc title: Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited” date: 2015-01-23 pages: extension: .txt txt: ./txt/cord-001527-x8yswoua.txt cache: ./cache/cord-001527-x8yswoua.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-001527-x8yswoua.txt' === file2bib.sh === id: cord-004469-m2fwefuy author: Rivera-Hernandez, Tania title: Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies date: 2020-03-10 pages: extension: .txt txt: ./txt/cord-004469-m2fwefuy.txt cache: ./cache/cord-004469-m2fwefuy.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-004469-m2fwefuy.txt' === file2bib.sh === id: cord-334463-nvu5tqxb author: Kim, Chonsaeng title: Echovirus 7 Entry into Polarized Intestinal Epithelial Cells Requires Clathrin and Rab7 date: 2012-04-10 pages: extension: .txt txt: ./txt/cord-334463-nvu5tqxb.txt cache: ./cache/cord-334463-nvu5tqxb.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-334463-nvu5tqxb.txt' === file2bib.sh === id: cord-341858-uz7vqq3r author: Davis, C. Todd title: Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness date: 2014-12-12 pages: extension: .txt txt: ./txt/cord-341858-uz7vqq3r.txt cache: ./cache/cord-341858-uz7vqq3r.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-341858-uz7vqq3r.txt' === file2bib.sh === id: cord-273391-vmtfn78x author: Li, Kun title: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection date: 2020-04-07 pages: extension: .txt txt: ./txt/cord-273391-vmtfn78x.txt cache: ./cache/cord-273391-vmtfn78x.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-273391-vmtfn78x.txt' === file2bib.sh === id: cord-297082-2rhoffx2 author: Yu, Changqing title: MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-297082-2rhoffx2.txt cache: ./cache/cord-297082-2rhoffx2.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-297082-2rhoffx2.txt' === file2bib.sh === id: cord-274663-zyzgk2z3 author: Chang, Stewart T. title: Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line date: 2011-09-20 pages: extension: .txt txt: ./txt/cord-274663-zyzgk2z3.txt cache: ./cache/cord-274663-zyzgk2z3.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-274663-zyzgk2z3.txt' === file2bib.sh === id: cord-274396-l611eisi author: Park, Su-Jin title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-274396-l611eisi.txt cache: ./cache/cord-274396-l611eisi.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-274396-l611eisi.txt' === file2bib.sh === id: cord-001152-v6uc0ijw author: Girardi, Erika title: Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells date: 2013-11-19 pages: extension: .txt txt: ./txt/cord-001152-v6uc0ijw.txt cache: ./cache/cord-001152-v6uc0ijw.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-001152-v6uc0ijw.txt' === file2bib.sh === id: cord-001223-6sb3ipab author: Lennemann, Nicholas J. title: Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1 date: 2014-01-28 pages: extension: .txt txt: ./txt/cord-001223-6sb3ipab.txt cache: ./cache/cord-001223-6sb3ipab.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-001223-6sb3ipab.txt' === file2bib.sh === id: cord-002467-b0p1b4g8 author: Leyva-Grado, Victor H. title: Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection date: 2017-03-28 pages: extension: .txt txt: ./txt/cord-002467-b0p1b4g8.txt cache: ./cache/cord-002467-b0p1b4g8.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-002467-b0p1b4g8.txt' === file2bib.sh === id: cord-252671-uf96jgig author: Wang, Yi title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism date: 2016-02-09 pages: extension: .txt txt: ./txt/cord-252671-uf96jgig.txt cache: ./cache/cord-252671-uf96jgig.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-252671-uf96jgig.txt' === file2bib.sh === id: cord-344227-rdlinzrn author: Gralinski, Lisa E. title: Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis date: 2018-10-09 pages: extension: .txt txt: ./txt/cord-344227-rdlinzrn.txt cache: ./cache/cord-344227-rdlinzrn.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-344227-rdlinzrn.txt' === file2bib.sh === id: cord-305336-wxiazglk author: Li, Ji Lian title: Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera date: 2014-01-21 pages: extension: .txt txt: ./txt/cord-305336-wxiazglk.txt cache: ./cache/cord-305336-wxiazglk.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-305336-wxiazglk.txt' === file2bib.sh === id: cord-353612-9ux181xg author: Josset, Laurence title: Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus date: 2013-04-30 pages: extension: .txt txt: ./txt/cord-353612-9ux181xg.txt cache: ./cache/cord-353612-9ux181xg.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-353612-9ux181xg.txt' === file2bib.sh === id: cord-012487-s920s5wb author: Noga, Marek J. title: Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-012487-s920s5wb.txt cache: ./cache/cord-012487-s920s5wb.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-012487-s920s5wb.txt' === file2bib.sh === id: cord-292742-mio4przi author: McAloose, Denise title: From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-292742-mio4przi.txt cache: ./cache/cord-292742-mio4przi.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-292742-mio4przi.txt' === file2bib.sh === id: cord-339269-7m53i1h9 author: Pope, Welkin H. title: Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood date: 2014-12-02 pages: extension: .txt txt: ./txt/cord-339269-7m53i1h9.txt cache: ./cache/cord-339269-7m53i1h9.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-339269-7m53i1h9.txt' === file2bib.sh === id: cord-348669-mizygp4j author: Beall, Anne title: Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A date: 2016-01-05 pages: extension: .txt txt: ./txt/cord-348669-mizygp4j.txt cache: ./cache/cord-348669-mizygp4j.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-348669-mizygp4j.txt' === file2bib.sh === id: cord-331361-pd9lt4n2 author: Mathieu, Cyrille title: Heparan Sulfate-Dependent Enhancement of Henipavirus Infection date: 2015-03-10 pages: extension: .txt txt: ./txt/cord-331361-pd9lt4n2.txt cache: ./cache/cord-331361-pd9lt4n2.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-331361-pd9lt4n2.txt' === file2bib.sh === id: cord-003143-n6b0r92e author: Zhao, Min title: Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses date: 2018-08-07 pages: extension: .txt txt: ./txt/cord-003143-n6b0r92e.txt cache: ./cache/cord-003143-n6b0r92e.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-003143-n6b0r92e.txt' === file2bib.sh === id: cord-287487-qeltdch7 author: Graepel, Kevin W. title: Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations date: 2017-11-07 pages: extension: .txt txt: ./txt/cord-287487-qeltdch7.txt cache: ./cache/cord-287487-qeltdch7.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-287487-qeltdch7.txt' === file2bib.sh === id: cord-279979-3ecnbqom author: Anthony, S. J. title: Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus date: 2017-04-04 pages: extension: .txt txt: ./txt/cord-279979-3ecnbqom.txt cache: ./cache/cord-279979-3ecnbqom.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-279979-3ecnbqom.txt' === file2bib.sh === id: cord-281389-sht0yx4a author: Tal, Michal Caspi title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-281389-sht0yx4a.txt cache: ./cache/cord-281389-sht0yx4a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-281389-sht0yx4a.txt' === file2bib.sh === id: cord-278303-lnrgom58 author: Björnsdóttir, Sigríður title: Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases date: 2017-08-01 pages: extension: .txt txt: ./txt/cord-278303-lnrgom58.txt cache: ./cache/cord-278303-lnrgom58.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-278303-lnrgom58.txt' === file2bib.sh === id: cord-287892-bnqmwst8 author: Hyser, Joseph M. title: Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity date: 2010-11-30 pages: extension: .txt txt: ./txt/cord-287892-bnqmwst8.txt cache: ./cache/cord-287892-bnqmwst8.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-287892-bnqmwst8.txt' === file2bib.sh === id: cord-256970-b8czrq29 author: Ielasi, Francesco S. title: Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins date: 2016-07-12 pages: extension: .txt txt: ./txt/cord-256970-b8czrq29.txt cache: ./cache/cord-256970-b8czrq29.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-256970-b8czrq29.txt' === file2bib.sh === id: cord-326160-mf0vh6iu author: de Wit, Emmie title: Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques date: 2014-08-12 pages: extension: .txt txt: ./txt/cord-326160-mf0vh6iu.txt cache: ./cache/cord-326160-mf0vh6iu.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-326160-mf0vh6iu.txt' === file2bib.sh === id: cord-003092-3owcqt3d author: Iketani, Sho title: Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation date: 2018-07-03 pages: extension: .txt txt: ./txt/cord-003092-3owcqt3d.txt cache: ./cache/cord-003092-3owcqt3d.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-003092-3owcqt3d.txt' === file2bib.sh === id: cord-303915-14yfs4pa author: Almazán, Fernando title: Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate date: 2013-09-10 pages: extension: .txt txt: ./txt/cord-303915-14yfs4pa.txt cache: ./cache/cord-303915-14yfs4pa.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-303915-14yfs4pa.txt' === file2bib.sh === id: cord-335938-hscgmis5 author: Gralinski, Lisa E. title: Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury date: 2013-08-06 pages: extension: .txt txt: ./txt/cord-335938-hscgmis5.txt cache: ./cache/cord-335938-hscgmis5.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-335938-hscgmis5.txt' === file2bib.sh === id: cord-348131-pkovyjo6 author: Li, Yize title: Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling date: 2019-11-12 pages: extension: .txt txt: ./txt/cord-348131-pkovyjo6.txt cache: ./cache/cord-348131-pkovyjo6.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-348131-pkovyjo6.txt' === file2bib.sh === id: cord-295946-p9enjxiq author: Hattori, Shin-ichiro title: GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-295946-p9enjxiq.txt cache: ./cache/cord-295946-p9enjxiq.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-295946-p9enjxiq.txt' === file2bib.sh === id: cord-351482-hzh5tyoo author: Peng, Xinxia title: Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection date: 2011-11-15 pages: extension: .txt txt: ./txt/cord-351482-hzh5tyoo.txt cache: ./cache/cord-351482-hzh5tyoo.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-351482-hzh5tyoo.txt' === file2bib.sh === id: cord-330315-upcf15q5 author: Oudshoorn, Diede title: Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication date: 2017-11-21 pages: extension: .txt txt: ./txt/cord-330315-upcf15q5.txt cache: ./cache/cord-330315-upcf15q5.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-330315-upcf15q5.txt' === file2bib.sh === id: cord-003609-p0ydzjre author: Goodman, Danielle E. title: Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date: 2019-04-23 pages: extension: .txt txt: ./txt/cord-003609-p0ydzjre.txt cache: ./cache/cord-003609-p0ydzjre.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-003609-p0ydzjre.txt' === file2bib.sh === id: cord-327660-p1b07b4t author: Wolf, Yuri I. title: Origins and Evolution of the Global RNA Virome date: 2018-11-27 pages: extension: .txt txt: ./txt/cord-327660-p1b07b4t.txt cache: ./cache/cord-327660-p1b07b4t.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-327660-p1b07b4t.txt' Que is empty; done journal-mbio-cord === reduce.pl bib === id = cord-263357-krvei97r author = Holmes, Kathryn V. title = The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia date = 2013-01-08 pages = extension = .txt mime = text/plain words = 2076 sentences = 83 flesch = 43 summary = Sequencing and bioinformatic analysis of the viral genomic RNA showed that it is a novel virus not previously detected in any other species and that its closest relatives are two Asian bat coronaviruses. demonstrated how state-of-the-art sequencing technology and bioinformatic analysis can quickly provide critical insight into the viral genome sequence, phylogeny, replication strategy, and potential drug and vaccine targets and generate tools to evaluate the possible epidemic risk associated with this novel human virus. In June 2012, a novel coronavirus, tentatively named HCoV-EMC (for Erasmus Medical Center where the initial genome sequence was done), was isolated in a monkey kidney cell line from a sputum specimen from a 60-year-old man from the Kingdom of Saudi Arabia who died of acute severe pneumonia and renal failure. The genomic analysis suggests that HCoV-EMC may be a zoonotic virus that spilled over to infect the 9 laboratory confirmed patients, either directly or indirectly, from an unknown reservoir, possibly a bat. cache = ./cache/cord-263357-krvei97r.txt txt = ./txt/cord-263357-krvei97r.txt === reduce.pl bib === id = cord-256970-b8czrq29 author = Ielasi, Francesco S. title = Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins date = 2016-07-12 pages = extension = .txt mime = text/plain words = 9315 sentences = 446 flesch = 46 summary = We first associated each edge with a relevance depending on the type of its connecting nodes (i.e., protein-glycan) according to the proposed weights (see equations 1 to 3 in the supplemental material) as a function of the lectin binding intensity measured via glycan array screenings. The hierarchical view (see Fig. 1 , 3, and 7) allowed linking of the experimentally determined lectin specificities (i.e., the glycan determinants) with the potential receptors (human or viral glycoproteins) and then linking of these glycoproteins to cell types/tissues and body systems. The LGI network of Candida Als and Epa adhesins N-Als1p has been shown to interact with fucose-containing glycans that are present in blood group antigens and preferentially with antigen H type 2 (22) . cache = ./cache/cord-256970-b8czrq29.txt txt = ./txt/cord-256970-b8czrq29.txt === reduce.pl bib === id = cord-274396-l611eisi author = Park, Su-Jin title = Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date = 2020-05-22 pages = extension = .txt mime = text/plain words = 4355 sentences = 208 flesch = 46 summary = While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. In order to determine the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine (HCQ) sulfate, or emtricitabine-tenofovir for treatment of SARS-CoV-2 infection, SARS-CoV-2 antibody-free ferrets (10/group) were inoculated with 10 5.8 50% tissue culture infective doses (TCID 50 )/ml of an NMC-nCoV02 strain through the intranasal (i.n.) route ( Fig. 1 ). Therefore, although clinical symptoms were attenuated in ferret groups treated with antiviral candidates, we also evaluated virus titers in respiratory and gastrointestinal tracts using nasal washes and stool samples, respectively, from SARS-CoV-2-infected ferrets. cache = ./cache/cord-274396-l611eisi.txt txt = ./txt/cord-274396-l611eisi.txt === reduce.pl bib === id = cord-252671-uf96jgig author = Wang, Yi title = The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism date = 2016-02-09 pages = extension = .txt mime = text/plain words = 7390 sentences = 389 flesch = 52 summary = title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production. The result of a dual-luciferase assay using the Renilla luciferase gene as a transfection control demonstrated that the SARS-CoV M gene rather than the S and E genes markedly increased IFN-␤ promoter activity (Fig. 1D) , whereas the valineto-alanine alteration at residue 68 of M protein completely abolished this induction, indicating that the specificity of M gene products played a role in this process. Taken together, our data indicate for the first time that SARS-CoV M protein may function as a novel cytosolic PAMP to activate IFN-␤ induction through an intracellular TLR-related signaling pathway in a TRAF3-independent manner. cache = ./cache/cord-252671-uf96jgig.txt txt = ./txt/cord-252671-uf96jgig.txt === reduce.pl bib === id = cord-003609-p0ydzjre author = Goodman, Danielle E. title = Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date = 2019-04-23 pages = extension = .txt mime = text/plain words = 8894 sentences = 487 flesch = 55 summary = RNA was purified from fractions containing monosomes MAV-1 Degrades PKR during Infection ® and polysomes and then used to generate cDNA, which we assayed for PKR mRNA by qPCR (Fig. 4C) . Thus, the 18-hpi time point is considered an early time point during MAV-1 infection of CMT93 cells, prior to DNA replication, suggesting the involvement of an early viral protein in PKR depletion. We examined PKR protein levels during MAV-1 infection and found that PKR was depleted from the cells as early as 12 hpi (Fig. 7) . While the PKR mRNAs in C57BL/6 MEFs were depleted 33% at 48 hpi and 40% at 72 hpi compared to mock-infected lysates, this was not sufficient to explain the 84% and 94% reductions, respectively, in PKR protein levels at those time points (Fig. 2B ). cache = ./cache/cord-003609-p0ydzjre.txt txt = ./txt/cord-003609-p0ydzjre.txt === reduce.pl bib === id = cord-001527-x8yswoua author = Lipsitch, Marc title = Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited” date = 2015-01-23 pages = extension = .txt mime = text/plain words = 4673 sentences = 205 flesch = 45 summary = title: Reply to "Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited" Likewise, Yoshihiro Kawaoka described the purpose of his ferret gain-of-transmission studies as "[t]o determine whether H5N1 viruses could be transmitted between humans" (25) , and the original reports of ferret transmission experiments say that pandemic potential is associated with the changes observed. Fouchier asserts that his claims of the likely low human transmissibility and lethality of the ferret-adapted strains should not be interpreted as reducing the likely benefits of the work for public health. In summary, while the possibility that ferret gain-of-transmission strains are attenuated in humans modestly reduces the risk estimate associated with producing and using them, it may nullify and even reverse the utility of such studies for public health. Studies on influenza virus transmission between ferrets; the public health risks revisited cache = ./cache/cord-001527-x8yswoua.txt txt = ./txt/cord-001527-x8yswoua.txt === reduce.pl bib === id = cord-003143-n6b0r92e author = Zhao, Min title = Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses date = 2018-08-07 pages = extension = .txt mime = text/plain words = 7938 sentences = 432 flesch = 55 summary = However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed crossbut biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Thus, to investigate the contribution of different cellular antigens of influenza viruses to biased cross-T-cell reactivities, we compared T-cell responses to H7N9 and pH1N1 among the members of the healthy population using overlapping peptides covering the M1 and NP proteins. Further analysis indicated that these peptides contained previously identified HLA class I-or class II-restricted epitopes (see Fig. S2D and H) and that the immunogenicity can be influenced by the substitutions in different AIVs. Phenotypes of the cross-reactive T-cell. cache = ./cache/cord-003143-n6b0r92e.txt txt = ./txt/cord-003143-n6b0r92e.txt === reduce.pl bib === id = cord-003092-3owcqt3d author = Iketani, Sho title = Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation date = 2018-07-03 pages = extension = .txt mime = text/plain words = 8948 sentences = 392 flesch = 46 summary = These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses. Deep genomic sequencing of nine sets of paired clinical samples (primary nasal swabs in viral transport medium) and culture isolates (culture harvest from zero passage virus) led to discovery of a number of HN mutations associated with rapid evolution in culture. To assess the frequency of mutations identified earlier, we also performed deep sequencing of 118 HPIV-3 clinical samples and culture isolates from the University of Washington Virology Laboratory, allowing us to confirm that the alterations associated with brief exposure to culture for viral isolation were almost entirely found in the sequences of culture isolates and found commonly within populations of viruses in those isolates. cache = ./cache/cord-003092-3owcqt3d.txt txt = ./txt/cord-003092-3owcqt3d.txt === reduce.pl bib === id = cord-001223-6sb3ipab author = Lennemann, Nicholas J. title = Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1 date = 2014-01-28 pages = extension = .txt mime = text/plain words = 5783 sentences = 282 flesch = 54 summary = In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Since complete deglycosylation of the core domains of GP1 did not negatively impact the expression of GP or the transduction of pseudotyped virions, we systematically combined N-linked glycan mutations in the MLD with our 7G mutant. Pseudovirion entry mediated by GP1⌬muc, GP, the 6G mutant, containing a fully deglycosylated glycan cap, and the GPm8G mutant containing a MLD that was fully deglycosylated for N-linked glycans were abrogated by treating Vero cells with the CatB inhibitor CA-074, which profoundly blocked CatB activity (Fig. S4A ). Our findings that deglycosylation of GP pseudovirions enhances the transduction of Vero cells and peritoneal macrophages provides evidence that the N-glycans on GP1 decrease the efficiency of the entry process. cache = ./cache/cord-001223-6sb3ipab.txt txt = ./txt/cord-001223-6sb3ipab.txt === reduce.pl bib === id = cord-001450-7vsdqhi0 author = Burgess, Stacey L. title = Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis date = 2014-11-04 pages = extension = .txt mime = text/plain words = 3996 sentences = 208 flesch = 42 summary = title: Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. It is also quite possible that mediators induced by the intestinal microbiota in the serum might influence the bone marrow in such a way as to prime DCs to provide protection against, or exacerbate, enteropathogen infections (27, 28) . histolytica colitis and that bone marrow dendritic cells (BM-DCs) derived from SFB-colonized mice were able to recapitulate protection in mice that had not been colonized with the bacteria. These data suggest that intestinal colonization with a commensal bacterium can alter bone marrow in such a way as to provide protection against parasite infection. Thus, as SFB increased frequency of intestinal DCs, IL-23, IL-17A expression, and circulating serum SAA, we examined the capacity of bone marrow DCs from SFB-infected mice to produce IL-23 in response to trophozoites. cache = ./cache/cord-001450-7vsdqhi0.txt txt = ./txt/cord-001450-7vsdqhi0.txt === reduce.pl bib === id = cord-004469-m2fwefuy author = Rivera-Hernandez, Tania title = Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies date = 2020-03-10 pages = extension = .txt mime = text/plain words = 5219 sentences = 267 flesch = 44 summary = Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. Groups of humanized plasminogen mice were immunized with Combo5 formulated with alum, Advax-2, Advax-4, SWE, LQ, LMQ, or SMQ adjuvant (Table 1) , while negative-control groups were immunized with phosphate-buffered saline (PBS) plus the corresponding adjuvant. Both Advax-2 and Advax-4 induced high antigen-specific antibody titers; however, the rate of survival of vaccinated mice was not significantly higher than that seen with the PBS-adjuvant control groups. Combo5/SMQ immunization resulted in strong secretion of IL-6 and IL-10 and of Th1-type cytokines IFN-␥ and TNF-␣, suggesting a potential role for Th1 responses in protection against invasive GAS infection following vaccination. cache = ./cache/cord-004469-m2fwefuy.txt txt = ./txt/cord-004469-m2fwefuy.txt === reduce.pl bib === id = cord-292883-7hvq9qaj author = Nguyen-Contant, Phuong title = S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit date = 2020-09-25 pages = extension = .txt mime = text/plain words = 5334 sentences = 264 flesch = 51 summary = RBD-binding MBCs sampled in the convalescent phase of SARS-CoV-2 infection expressed Abs with relatively low numbers of V gene mutations, suggesting that this component of the response largely reflected naive B cell activation by novel epitopes (20) . Approximately one-third of non-SARS-CoV-2-exposed subjects in the healthy donor cohort had low levels of serum IgG against the S and N proteins of SARS-CoV-2, likely reflecting cross-reactivity with seasonal HCoVs (Fig. 1A) . Since the healthy donor samples in our analysis were collected 6 to 10 years before the emergence of SARS-CoV-2, we considered the possibility that a recently circulating HCoV was responsible for the higher anti-OC43 S IgG titers in the convalescent subjects. In contrast, IgG MBCs reactive to the S proteins of the HCoVs OC43 and 229E and the control proteins H1 and TTd were detected in nearly 50% or more of non-SARS-CoV-2-exposed subjects, consistent with the higher levels of serum IgG against these antigens (Fig. 2E to H) . cache = ./cache/cord-292883-7hvq9qaj.txt txt = ./txt/cord-292883-7hvq9qaj.txt === reduce.pl bib === id = cord-260087-9o9tb28h author = Furmanski, Martin title = The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards date = 2015-09-29 pages = extension = .txt mime = text/plain words = 648 sentences = 34 flesch = 45 summary = R ozo and Gronvall, in "The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate" (1), confirmed the laboratory origin of the 1977 influenza pandemic and judged it was unintentional, but they concluded that its "relevance to GoF research is greatly diminished if the 1977 epidemic was the result of a vaccine trial or vaccine development gone awry; these are both more plausible explanations than a single laboratory accident." Rozo and Gronvall also stated that, "in 1977, influenza research was performed without modern biosafety regulations and protective equipment, making the lab accident hypothesis much less relevant to the modern GoF debate." However, the current record of containment of high-consequence pathogens is hardly reassuring. Activities at the select agent laboratory at the Tulane National Primate Research Center remain suspended after Burkholderia pseudomallei, the agent of melioidosis, escaped containment and caused multiple primate infections in an outdoor primate facility (5, 6) . cache = ./cache/cord-260087-9o9tb28h.txt txt = ./txt/cord-260087-9o9tb28h.txt === reduce.pl bib === id = cord-001340-kqcx7lrq author = Ladner, Jason T. title = Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing date = 2014-06-17 pages = extension = .txt mime = text/plain words = 2512 sentences = 121 flesch = 40 summary = Genome sequences play a critical role in our understanding of viral evolution, disease epidemiology, surveillance, diagnosis, and countermeasure development and thus represent valuable resources which must be properly documented and curated to ensure future utility. Here, we outline a set of viral genome quality standards, similar in concept to those proposed for large DNA genomes (4) but focused on the particular challenges of and needs for research on small RNA/ DNA viruses, including characterization of the genomic diversity inherent in all viral samples/populations. Therefore, we have used technology-agnostic criteria to define five standard categories designed to encompass the levels of completeness most often encountered in viral sequencing projects. There is a trend toward requiring a complete genome sequence when a description of a novel virus is being published, and we agree that this is a good goal; however, the amount of time and resources required to complete the last 1 to 2% of a viral genome is often cost and time prohibitive for projects sequencing a large number of samples, and in most cases the very ends of the segments are not essential for proper identification and characterization. cache = ./cache/cord-001340-kqcx7lrq.txt txt = ./txt/cord-001340-kqcx7lrq.txt === reduce.pl bib === id = cord-001152-v6uc0ijw author = Girardi, Erika title = Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells date = 2013-11-19 pages = extension = .txt mime = text/plain words = 7021 sentences = 383 flesch = 52 summary = Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21to 28-nucleotide (nt) species during infection. We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs. Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability. The identification of small RNAs from RNA viruses could be seen either as a result of a productive mechanism for the pathogen (as for virus-encoded miRNAs) or as the consequence of a host response to control the infection by degrading viral RNAs. SINV expresses four enzymes that play key functions during the viral replicative cycle. cache = ./cache/cord-001152-v6uc0ijw.txt txt = ./txt/cord-001152-v6uc0ijw.txt === reduce.pl bib === id = cord-287487-qeltdch7 author = Graepel, Kevin W. title = Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations date = 2017-11-07 pages = extension = .txt mime = text/plain words = 7470 sentences = 467 flesch = 49 summary = Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. High-or low-fidelity variants are described for many RNA viruses infecting animals, including the coronaviruses (CoVs) murine hepatitis virus (MHV-A59) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) (13) (14) (15) (16) (17) , as well as foot-and-mouth disease virus (18) (19) (20) (21) (22) , poliovirus (23) (24) (25) (26) (27) (28) (29) , Chikungunya virus (30, 31) , influenza virus (32) , coxsackievirus B3 (33, 34) , and human enterovirus 71 (35) (36) (37) . The evolved mutations in MHV-ExoN(-) nsp14 and nsp12, which encodes the RdRp, accounted for only part of the increased nucleoside analogue resistance of MHV-ExoN(-) P250, implicating multiple replicase proteins in adaptation for viral fitness. cache = ./cache/cord-287487-qeltdch7.txt txt = ./txt/cord-287487-qeltdch7.txt === reduce.pl bib === id = cord-297082-2rhoffx2 author = Yu, Changqing title = MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date = 2020-09-15 pages = extension = .txt mime = text/plain words = 6423 sentences = 410 flesch = 61 summary = Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. As a control, serine incorporator 5 (SERINC5) protein In addition, FLAG-tagged furin was expressed with HA-tagged human MARCH8 and GPΔMLD in 293T cells. In addition, when the furin-VN/GP-VC pair was expressed with MARCH8, their colocalization was also detected (Fig. 2C ), confirming that these three molecules form a complex in live cells. MARCH8 proteins from different species strongly increased GP 1 and GP 1 ΔMLD expression in cells but completely blocked their secretions (Fig. 7C, lanes 1 to 8) . cache = ./cache/cord-297082-2rhoffx2.txt txt = ./txt/cord-297082-2rhoffx2.txt === reduce.pl bib === id = cord-012487-s920s5wb author = Noga, Marek J. title = Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date = 2020-08-18 pages = extension = .txt mime = text/plain words = 7414 sentences = 391 flesch = 49 summary = By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. In order to understand how the model Gram-negative species Escherichia coli coordinates membrane synthesis with growth, we quantified substrates and enzymes of the fatty acid and PL synthesis pathways under both steady-state and dynamic conditions. The trends in substrate, enzyme, and intermediate concentrations observed in ppGpp-limited cultures are consistent with growth regulating PL flux via posttranslational control-not transcriptional control-of PlsB. To test whether regulation of PlsB activity is sufficient to control steady-state PL synthesis, we constructed a simplified differential equation model that describes fatty acid, LPS initiation, and PL biosynthesis ( Fig. 2A ; see also Text S1 and Table S1 ). cache = ./cache/cord-012487-s920s5wb.txt txt = ./txt/cord-012487-s920s5wb.txt === reduce.pl bib === id = cord-305698-fjd0rsrf author = Imperiale, Michael J. title = Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus date = 2014-12-12 pages = extension = .txt mime = text/plain words = 1528 sentences = 79 flesch = 51 summary = title: Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus We have numerous concerns with this third stoppage, including the timing of the announcement relative to the ongoing debate, the vagueness in the wording of the statement, and the potential effects on the fields of influenza virus and coronavirus research. Second, we worry about the meaning of "reasonably anticipated." Obviously this phrase is very subjective, and similar wording in the definition of dual use research of concern (DURC) has already made assessments of what constitutes DURC very problematic for journals and authors (10) . The current pause affects two dozen studies that include experiments to develop rodent models of coronavirus research (11) . Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness cache = ./cache/cord-305698-fjd0rsrf.txt txt = ./txt/cord-305698-fjd0rsrf.txt === reduce.pl bib === id = cord-286587-x0wqtlxh author = Fedson, David S. title = Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection date = 2020-03-20 pages = extension = .txt mime = text/plain words = 1052 sentences = 72 flesch = 49 summary = Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection. We believe that investigators in China and elsewhere should undertake studies of patients with severe COVID-19 infection to determine whether targeting the host response with widely available and inexpensive generic drugs, like ARBs and statins, will improve their chances of survival. Convincing evidence of the effectiveness of this treatment would suggest a syndromic approach to treating patients with other emerging infectious diseases, like Ebola and pandemic influenza, as well as everyday illnesses, like sepsis and pneumonia (19) . Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola Treating the host response to Ebola virus disease with generic statins and angiotensin receptor blockers cache = ./cache/cord-286587-x0wqtlxh.txt txt = ./txt/cord-286587-x0wqtlxh.txt === reduce.pl bib === id = cord-327660-p1b07b4t author = Wolf, Yuri I. title = Origins and Evolution of the Global RNA Virome date = 2018-11-27 pages = extension = .txt mime = text/plain words = 13927 sentences = 658 flesch = 45 summary = The current RdRp tree topology combined with gene gain-loss reconstruction suggests the following evolutionary scenario for branch 1 ( Fig. 2A) : a levivirus-like ancestor that, like the extant members of the Leviviridae, possessed a capsid protein unrelated to SJR-CP (19, 52) gave rise to naked eukaryotic RNA replicons known as "mitoviruses" and "narnaviruses." These replicons consist of a single RdRp gene (Fig. 2B ) and replicate in mitochondria and in the cytosol of the host cells of fungal and invertebrate hosts, respectively (the latter hosts were identified in metaviromic holobiont analyses) (14, 53) . This genome architecture could hint at an ancestral flavivirus genome that was assembled from genes borrowed from preexisting viruses, one of which possessed a divergent "tombus-like virus" RdRp. Although the origins of branch 3 are murky, major trends in its subsequent evolution clearly included lineage-specific gene capture, starting with helicases and CapEs in the ancestors of the major lineages and followed by diverse genes in smaller groups (Fig. 4B) . cache = ./cache/cord-327660-p1b07b4t.txt txt = ./txt/cord-327660-p1b07b4t.txt === reduce.pl bib === id = cord-298773-vnmc6nqd author = Pfeiffer, Julie K. title = Is the Debate and “Pause” on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? date = 2015-01-20 pages = extension = .txt mime = text/plain words = 1713 sentences = 87 flesch = 50 summary = title: Is the Debate and "Pause" on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? This letter is about the potential impact of the debate and pause on graduate students and postdoctoral fellows and how their future plans may be affected. To gain initial insight into how the debate and research pause have affected trainees, I created an informal survey 2 days before the National Academy of Sciences meeting. These projects involve a subset of "gain of function" experiments designed to create mouse adapted viral strains, generate drug resistant viruses to understand drug mechanisms of action, understand host immunity by analyzing viruses with resistance to certain host immune pathways, and to study factors that influence transmission by the respiratory route (which was made famous by work from the Kawaoka and Fouchier labs in 2012). Third, the debate and research pause are influencing future plans of virology trainees. cache = ./cache/cord-298773-vnmc6nqd.txt txt = ./txt/cord-298773-vnmc6nqd.txt === reduce.pl bib === id = cord-001528-33f94doo author = Fouchier, Ron A. M. title = Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited date = 2015-01-23 pages = extension = .txt mime = text/plain words = 3522 sentences = 141 flesch = 40 summary = Initial calculations of the potential risks associated with research on influenza virus transmission via respiratory droplets or aerosols between ferrets (1-4) used reports on select agent theft, loss, and release collected by the U.S. Centers for Disease Control and Prevention (CDC) from 2004 to 2010 (7) to calculate the probability of occurrence of LAIs. Although these reports have limitations (1, 4, 7) , they provide the most recent account of LAIs in the United States and probably reflect the current state of the art in biosafety and biosecurity practices better than older studies on laboratory incidents (8, 9) , e.g., as a consequence of the implementation of the U.S. select agent program and best practices developed in biosafety and biosecurity in general over the last decades. cache = ./cache/cord-001528-33f94doo.txt txt = ./txt/cord-001528-33f94doo.txt === reduce.pl bib === id = cord-281389-sht0yx4a author = Tal, Michal Caspi title = Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date = 2020-06-23 pages = extension = .txt mime = text/plain words = 7629 sentences = 382 flesch = 46 summary = Examination of a publicly available gene expression data set (Gene Expression Omnibus [GEO] accession number GSE147507) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of A549 human lung cells also showed a significant upregulation of CD47 compared to mock-infected controls (Fig. 1D ). Multiple PBMC subsets showed significantly upregulated CD47 expression in response to Borrelia burgdorferi infection compared to naive cells (Fig. 1E) . Overall, the combined in vivo and in vitro results from multiple pathogen infections in both human and mouse cells indicated that the upregulation of CD47 was a conserved host response possibly related to host sensing mechanisms. Compared to healthy controls, monocytes and DCs from HCV patients demonstrated a sustained upregulation of CD47 at all treatment time points, including the 6-month posttreatment time point ( Fig. 3B (B) CD47 MFI on human total PBMCs from 4 separate donors stimulated with titrated concentrations of R848 from 0.1 g/ml to 10 g/ml, as indicated, for 48 h. cache = ./cache/cord-281389-sht0yx4a.txt txt = ./txt/cord-281389-sht0yx4a.txt === reduce.pl bib === id = cord-002467-b0p1b4g8 author = Leyva-Grado, Victor H. title = Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection date = 2017-03-28 pages = extension = .txt mime = text/plain words = 5948 sentences = 297 flesch = 43 summary = Similarly, in wild-type mice infected with NL/09 virus, we P2X7 Receptor in Influenza Immunopathology ® observed a significant reduction in body weight at days 4 to 8 postinfection (P Ͻ 0.05) (Fig. 2C) . Reduced virus titers were observed in the lungs of the P2X7r KO mice compared to the wild-type mice, particularly in the samples collected on day 7 postinfection, although these differences were not statistically significant (P ϭ 0.1) (Fig. 3A) . In this study, we showed that mice lacking the purinergic receptor P2X7 have a better clinical outcome after influenza A virus infection characterized by an increased survival rate with an overall reduced immunopathology of the lungs compared to the wild-type mice. Activation of the purinergic receptor P2X7 signaling by increased levels of extracellular ATP caused by influenza virus infection leads to an exacerbated immune response characterized by increased production of proinflammatory cytokines, induction of apoptosis, increased influx of neutrophils in the airways, and development of lung histopathology. cache = ./cache/cord-002467-b0p1b4g8.txt txt = ./txt/cord-002467-b0p1b4g8.txt === reduce.pl bib === id = cord-326160-mf0vh6iu author = de Wit, Emmie title = Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques date = 2014-08-12 pages = extension = .txt mime = text/plain words = 6428 sentences = 318 flesch = 42 summary = Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. To elucidate global host responses specifically associated with sites of virus-induced airway injury in influenza virus A/Anhui/1/2013-infected macaques, we used microarrays to assess transcriptional profiles induced in lung lesions compared to the adjacent lung tissue. We identified ten compounds in IPA (Table 1) , four of which were perturbagens listed in CMap. We identified two compounds that met our criteria in IPA and CMap, rosiglitazone and simvastatin, predicted to have inhibitory effects on pathological host responses associated with lesions in influenza virus A/Anhui/1/2013-infected animals ( Table 1) . cache = ./cache/cord-326160-mf0vh6iu.txt txt = ./txt/cord-326160-mf0vh6iu.txt === reduce.pl bib === id = cord-296028-hqrd1e8p author = Rozell, Daniel J. title = Assessing and Managing the Risks of Potential Pandemic Pathogen Research date = 2015-07-21 pages = extension = .txt mime = text/plain words = 2584 sentences = 133 flesch = 45 summary = Ultimately, the purpose of summarizing and critiquing some of the arguments within the GOF/PPP debate is to emphasize the many epistemic and ethical value judgments inherent to RBA and to provide evidence for prior claims that a consensus-building quantitative assessment is unlikely (1). As summarized here, many of the disagreements within the GOF/PPP debate involve epistemic and ethical value judgments that suggest that definitive quantitative risk-benefit analysis is not possible. Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion mBio addresses the pause in gain-offunction (GOF) experiments involving pathogens with pandemic potential (PPP) Conducting risk and benefit analysis on gain-of-function research involving pathogens with pandemic potential An epistemological perspective on the value of gain-of-function experiments involving pathogens with pandemic potential Vagueness and costs of the pause on gain-of-function (GOF) experiments on pathogens with pandemic potential, including influenza virus cache = ./cache/cord-296028-hqrd1e8p.txt txt = ./txt/cord-296028-hqrd1e8p.txt === reduce.pl bib === id = cord-335432-9aszklx3 author = Duprex, W. Paul title = Falling down the Rabbit Hole: aTRIP Toward Lexiconic Precision in the “Gain-of-Function” Debate date = 2014-12-12 pages = extension = .txt mime = text/plain words = 2438 sentences = 122 flesch = 50 summary = (B) Dual-use research of concern (DURC) is a small subset of DUR involving life sciences research that, based on current understanding, can reasonably be anticipated to provide knowledge, information, products, or technologies that could be directly misapplied, posing a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. (D) Although spanning all of microbiological research, much of the DURC debate has focused on virology, where selection processes of circulating and synthetically generated agents have been used to enhance transmission. For some, gain of function causes the most concern, although even for the influenza transmission studies, it is simplistic to focus on only one phenotype/ one function as a range or on infectivity changed during selection of mammal-adapted avian influenza viruses. Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion cache = ./cache/cord-335432-9aszklx3.txt txt = ./txt/cord-335432-9aszklx3.txt === reduce.pl bib === id = cord-303915-14yfs4pa author = Almazán, Fernando title = Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate date = 2013-09-10 pages = extension = .txt mime = text/plain words = 7132 sentences = 336 flesch = 50 summary = The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. Using this clone, recombinant MERS-CoV (rMERS-CoV) deletion mutants were constructed lacking genes nonessential for virus replication. An infectious cDNA clone was assembled as a BAC under the control of the cytomegalovirus (CMV) immediate-early pro-moter, based on the genome sequence of the MERS-CoV-EMC12 strain (GenBank accession number JX869059) (15) . Based on published data showing that the deletion of CoV E protein resulted in either replication-competent, propagation-defective viruses (24) or attenuated viruses (25, 26, 31) , a cDNA clone with the E gene deleted (pBAC-MERS-⌬E) was constructed from pBAC-MERS FL . cache = ./cache/cord-303915-14yfs4pa.txt txt = ./txt/cord-303915-14yfs4pa.txt === reduce.pl bib === id = cord-274663-zyzgk2z3 author = Chang, Stewart T. title = Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line date = 2011-09-20 pages = extension = .txt mime = text/plain words = 6991 sentences = 358 flesch = 48 summary = Using NGS, we detected small but significant changes in host gene expression affecting T cell function that coincided with the initiation of viral RNA production at 12 h postinfection (hpi). In addition, by using NGS, we observed the dramatic expansion of viral mRNA expression and detected new viral splice events occurring during viral replication and differential expression of noncoding RNA species, including microRNA host genes. In our data set, we observed no change in the expression of the Crm1-encoding gene XPO1, but several members of the Ran signaling pathway were downregulated, suggesting that the overall export of unspliced viral RNA was suppressed (see Fig. S5B in the supplemental material; data not shown for XPO1). The regulation of these and transcription factors specific for other functions (e.g., EGR1, KLF13, and MYC) may explain how HIV initiated replication with minimal disruption to host gene expression at 12 hpi but elicited larger-scale changes later in infection. cache = ./cache/cord-274663-zyzgk2z3.txt txt = ./txt/cord-274663-zyzgk2z3.txt === reduce.pl bib === id = cord-337492-o6sy4zi4 author = Baric, Ralph S. title = Next-Generation High-Throughput Functional Annotation of Microbial Genomes date = 2016-10-04 pages = extension = .txt mime = text/plain words = 3026 sentences = 144 flesch = 34 summary = The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community. Unlike large-scale genome-sequencing or structural-genomics efforts, the functional annotation of uncharacterized genes is not well developed technologically, and therefore, the scientific community cannot rely on a well-defined, mature set of experimental approaches. The NIAID has implemented a program aimed at assigning functions to open reading frames (ORFs) and small noncoding RNAs (ncRNAs) that have been discovered by large-scale sequencing efforts to begin addressing this gap in our understanding of bacterial and viral gene function. cache = ./cache/cord-337492-o6sy4zi4.txt txt = ./txt/cord-337492-o6sy4zi4.txt === reduce.pl bib === id = cord-353612-9ux181xg author = Josset, Laurence title = Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus date = 2013-04-30 pages = extension = .txt mime = text/plain words = 6299 sentences = 303 flesch = 49 summary = Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. In addition, several kinase inhibitors (including SB203580, LY294002, and U0126) and a glucocorticoid (dexamethasone) were also predicted to be negative regulators of genes changed similarly after SARS-CoV and HCoV-EMC infection at late times postinfection (see Table S2 in the supplemental material). Importantly, this kinase inhibitor was predicted to regulate genes that were DE similarly by SARS-CoV and HCoV-EMC at late times postinfection (see Table S2 in the supplemental material) and could therefore inhibit both viruses' replication. cache = ./cache/cord-353612-9ux181xg.txt txt = ./txt/cord-353612-9ux181xg.txt === reduce.pl bib === id = cord-330315-upcf15q5 author = Oudshoorn, Diede title = Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication date = 2017-11-21 pages = extension = .txt mime = text/plain words = 7718 sentences = 349 flesch = 50 summary = Using electron tomography, we demonstrate that for both MERS-CoV and SARS-CoV coexpression of nsp3 and nsp4 is required and sufficient to induce DMVs. Coexpression of MERS-CoV nsp3 and nsp4 either as individual proteins or as a self-cleaving nsp3-4 precursor resulted in very similar DMVs, and in both setups we observed proliferation of zippered ER that appeared to wrap into nascent DMVs. Moreover, when inactivating nsp3-4 polyprotein cleavage by mutagenesis, we established that cleavage of the nsp3/nsp4 junction is essential for MERS-CoV DMV formation. To study whether the transmembrane nsp's of MERS-CoV are able to induce DMV formation, we expressed nsp3 and nsp4 from a CAG promoter (43) either by cotransfection of cells with plasmids encoding individual proteins or by transfection with a single plasmid encoding a self-cleaving nsp3-4 polyprotein fragment ( Fig. 1A ; Table S1 ). The observation of maze-like bodies and circular double-membrane profiles, which were interpreted to represent tubular structures, led these authors to conclude that coexpression of SARS-CoV nsp3 and nsp4 was not sufficient for DMV formation. cache = ./cache/cord-330315-upcf15q5.txt txt = ./txt/cord-330315-upcf15q5.txt === reduce.pl bib === id = cord-289360-h6wvx7gw author = Imperiale, Michael J. title = The Importance of Virology at a Time of Great Need and Great Jeopardy date = 2015-03-10 pages = extension = .txt mime = text/plain words = 1290 sentences = 59 flesch = 51 summary = journal: mBio Viruses account for up to 20% of all human cancers, and although a large percentage of new human papillomavirus (HPV) and HBV infections can now be prevented by vaccination, many are already infected, and the vaccines are not being used to their full potential. The tremendous reduction in mortality from such diseases as variola, measles, and rubella came about only because the causative viruses were identified, cultivated, attenuated, and made into effective vaccines by biomedical research. While we scientists cannot directly control funding or regulations, we can take charge of some aspects of the research enterprise in a way to ensure that it continues to benefit society. This requires engaging our elected officials both directly and indirectly by continuing to educate them and the public at large about the importance of fundamental research in infectious diseases. cache = ./cache/cord-289360-h6wvx7gw.txt txt = ./txt/cord-289360-h6wvx7gw.txt === reduce.pl bib === id = cord-308848-chvvtr0d author = Fidel, Paul L. title = Reply to Özdemir, “Measles-Mumps-Rubella Vaccine and COVID-19 Relationship” date = 2020-09-22 pages = extension = .txt mime = text/plain words = 558 sentences = 33 flesch = 52 summary = While the current clinical trials are not investigating this issue directly, we have focused on the MMR vaccine as it is widely available and has the potential for any or all of the three components to induce the MDSCs. However, based on our data in the animal model of fungal/bacterial sepsis, very strong long-lasting protection is afforded from one administration of the attenuated fungal isolate (7) . Finally, while it is true that we do not know how long the trained innate immunity persists, the randomized clinical trial of MMR versus placebo in health care workers and the nonhuman primate study that will test MMR or BCG in a model of COVID-19 infection will go far to answer these questions. To date, the trained innate response with BCG suggests the immunity is functional for approximately 1 year based on infant vaccinations (8) . Immune protection against lethal fungal-bacterial intra-abdominal infections cache = ./cache/cord-308848-chvvtr0d.txt txt = ./txt/cord-308848-chvvtr0d.txt === reduce.pl bib === id = cord-280001-y7pvj2l1 author = Patel, Robin title = Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19 date = 2020-03-26 pages = extension = .txt mime = text/plain words = 1785 sentences = 77 flesch = 46 summary = If the test is positive though, the result is most likely correct, although stray viral RNA that makes its way into the testing process (for example, as the specimen is being collected or as a result of specimen cross-contamination or testing performed by a laboratory worker who is infected with SARS-CoV-2 [these are just some examples]) could conceivably result in a falsely positive result. Testing patients for SARS-CoV-2 helps identify those who are infected, which is useful for individual patient management, as well as for implementation of mitigation strategies to prevent spread in health care facilities and in the community alike (Fig. 1) . Given that SARS-CoV-2 can infect anyone and result in transmission prior to the onset of symptoms or even possibly without individuals ever developing symptoms, testing asymptomatic patients could even be considered. Finally, serologic testing can possibly be used diagnostically to test viral RNA-negative individuals presenting late in their illness. cache = ./cache/cord-280001-y7pvj2l1.txt txt = ./txt/cord-280001-y7pvj2l1.txt === reduce.pl bib === id = cord-264050-6zpw6itb author = Pirofski, Liise-anne title = Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response date = 2017-12-12 pages = extension = .txt mime = text/plain words = 2752 sentences = 121 flesch = 36 summary = The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction. However, the emergence of Cryptococcus gattii in apparently healthy persons in the Pacific Northwest (7) and the unexpected appearance of immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcosis in patients with HIV/AIDS after initiation of antiretroviral therapy (ART) (8, 9) revealed that the host immune response itself can contribute to the pathogenesis of cryptococcosis. The emergence of IRIS-associated cryptococcosis in the setting of ART initiation provided clear evidence that host damage in patients with cryptococcal disease may be driven by inflammation (12) . Chemokine levels and chemokine receptor expression in the blood and the cerebrospinal fluid of HIV-infected patients with cryptococcal meningitis and cryptococcosis-associated immune reconstitution inflammatory syndrome cache = ./cache/cord-264050-6zpw6itb.txt txt = ./txt/cord-264050-6zpw6itb.txt === reduce.pl bib === id = cord-348669-mizygp4j author = Beall, Anne title = Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A date = 2016-01-05 pages = extension = .txt mime = text/plain words = 6021 sentences = 293 flesch = 43 summary = title: Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. While the recombinant icPEDV replicated the clinical phenotypes of parental PC22A in vivo, icPEDV-⌬ORF3-RFP infection resulted in a partial attenuation in pigs based on lower diarrhea scores. Both the parental PEDV PC22A strain and its derivative recombinant cloned virus were genetically stable and fully pathogenic in neonatal gnotobiotic pigs, demonstrating that icPEDV provides not only a strategy that allows for the systematic evaluation of the role of viral genes in pathogenesis, tropism, and virulence but also a translational platform for the development of rationally attenuated live virus vaccines. cache = ./cache/cord-348669-mizygp4j.txt txt = ./txt/cord-348669-mizygp4j.txt === reduce.pl bib === id = cord-334463-nvu5tqxb author = Kim, Chonsaeng title = Echovirus 7 Entry into Polarized Intestinal Epithelial Cells Requires Clathrin and Rab7 date = 2012-04-10 pages = extension = .txt mime = text/plain words = 6207 sentences = 325 flesch = 48 summary = We found that drugs, small interfering RNAs (siRNAs), and dominant negative mutants that target factors required for clathrin-mediated endocytosis, including clathrin and dynamin, inhibited both EV7 infection and internalization of virions from the cell surface. We previously (19) observed that, to infect polarized epithelium, CVB3 binds DAF on the cell surface, moves to the tight junction, and then enters the cell by an unusual mechanism that is independent of both dynamin and clathrin but which requires caveolin; contact with CAR in the tight junction leads to an essential conformational change in the CVB3 virion, but disruption of the capsid does not appear to occur until the virus has moved to an unidentified intracellular compartment. We had previously observed that CVB3 infection of Caco-2 cells occurs by a complex process that depends on caveolin but not dynamin-2, appears to be independent of clathrin-mediated endocytosis, and is inhibited by depletion of membrane cholesterol (19) . cache = ./cache/cord-334463-nvu5tqxb.txt txt = ./txt/cord-334463-nvu5tqxb.txt === reduce.pl bib === id = cord-303262-grrd6jmt author = Tournier, Jean-Nicolas title = Pandemic Legion History More Complex than Previously Thought date = 2020-10-09 pages = extension = .txt mime = text/plain words = 699 sentences = 34 flesch = 47 summary = Morens and colleagues describe in the "early pandemic history" section the story of pathogens emerging around 12,000 years ago at the time of Neolithic agricultural revolution. As such, diseases such as "measles, smallpox, tuberculosis (TB), [and] gastric cancer (caused by Helicobacter pylori)" are cited as consequences of "conditions of intense human-animal proximity and environmental alterations." This assertion of the dating of the origin of these aforementioned pathogens is partially misleading. Both viruses (i.e., those causing measles and smallpox) emerged probably much later, while Mycobacterium tuberculosis and Helicobacter pylori started their association with humans before the agricultural revolution. For smallpox, the exact date of divergence of variola virus (VARV) from a zoonotic strain is more disputed, as molecular data gave an estimation of emergence for the most recent common ancestor between the 16th and the 17th century, while skin lesions seen in the mummy of Ramses V, who died in 1157 BCE, suggested earlier interactions (6) . cache = ./cache/cord-303262-grrd6jmt.txt txt = ./txt/cord-303262-grrd6jmt.txt === reduce.pl bib === id = cord-344227-rdlinzrn author = Gralinski, Lisa E. title = Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis date = 2018-10-09 pages = extension = .txt mime = text/plain words = 6557 sentences = 309 flesch = 43 summary = As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Mice deficient in C3 (C3 -/-), the central protein of the complement signaling pathway, were protected from SARS-CoV-induced weight loss and had reduced pathology, improved respiratory function, and lower levels of inflammatory cytokines/chemokines in the lung and periphery. Immunohistochemical staining revealed that SARS-CoV MA15 infection induced complement deposition in the lung (Fig. 4) , similar to that associated with pathogenesis in Ross River virus-infected mice (41) and some influenza virus infections (34) , and it is likely that complement deposition contributes to pulmonary disease and inflammatory cell recruitment. cache = ./cache/cord-344227-rdlinzrn.txt txt = ./txt/cord-344227-rdlinzrn.txt === reduce.pl bib === id = cord-287892-bnqmwst8 author = Hyser, Joseph M. title = Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity date = 2010-11-30 pages = extension = .txt mime = text/plain words = 7093 sentences = 397 flesch = 49 summary = The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. We previously showed that NSP4 forms a novel vesicular compartment concomitantly with increased [Ca 2ϩ ]cyto (45) and that these structures associate with the autophagy protein LC3 and surround viroplasms, cytoplasmic inclusions in rotavirus-infected cells that support virus replication. cache = ./cache/cord-287892-bnqmwst8.txt txt = ./txt/cord-287892-bnqmwst8.txt === reduce.pl bib === id = cord-278303-lnrgom58 author = Björnsdóttir, Sigríður title = Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases date = 2017-08-01 pages = extension = .txt mime = text/plain words = 6243 sentences = 305 flesch = 51 summary = This study represents the first time that whole-genome sequencing has been used to investigate an epidemic on a national scale to identify the likely causative agent and the link to an associated zoonotic infection. This isolation of the population has meant that Icelandic horses have remained free from most common contagious diseases of Equidae, including equine influenza, equine rhinopneumonitis, equine viral arteritis, Rhodococcus equi infection, and strangles (Streptococcus equi subsp. Removal of strains with identical sequences that were recovered from the same animal on the same date produced a data set of 59 ST209 isolates with 434 polymorphic core genome positions (Table S2 ). zooepidemicus recovered from Icelandic horses in this study are also likely to have caused clinical signs of disease. zooepidemicus likely persisted in the horses at the Icelandic Veterinary Institute, accruing nucleotide diversity over time within this isolated population. cache = ./cache/cord-278303-lnrgom58.txt txt = ./txt/cord-278303-lnrgom58.txt === reduce.pl bib === id = cord-273391-vmtfn78x author = Li, Kun title = Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection date = 2020-04-07 pages = extension = .txt mime = text/plain words = 5258 sentences = 291 flesch = 53 summary = title: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. As shown in Fig. 3B to D, we observed a significant increase in the Immunization with PIV5 Expressing MERS-CoV Spike ® percentage and total number of CD8 ϩ -IFN-␥ ϩ cells in the lungs of PIV5-MERS-Simmunized mice in comparison to those infected with PIV5-GFP virus, consistent with a MERS-S-specific primary CD8 T cell response in the lungs. The finding that PIV5 expressing MERS S protected mice against lethal MERS-CoV challenge at a single low dose of 10 4 PFU suggests its potential use as a vaccine vector for emerging viruses such as SARS-CoV-2. cache = ./cache/cord-273391-vmtfn78x.txt txt = ./txt/cord-273391-vmtfn78x.txt === reduce.pl bib === id = cord-279979-3ecnbqom author = Anthony, S. J. title = Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus date = 2017-04-04 pages = extension = .txt mime = text/plain words = 5345 sentences = 247 flesch = 48 summary = Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Predicting the interactions of virus binding domains with a particular host receptor (for example, the human MERS-CoV receptor DPP4) is possible through the use of structural modeling and the generation of infectious clones. This virus (PREDICT/PDF-2180) shares the same putative S1 subunit recombination that was observed in NeoCoV, allowing us to also consider whether the spike recombination was critical for the emergence of MERS-CoV in humans. Based on the current criteria for species demarcation established by the International Committee for the Taxonomy of Viruses (Ͼ90% amino acid sequence identity in the replicase proteins), PREDICT/PDF-2180 shares sufficient genetic identity to MERS-CoV to be considered a member of the MERS-like Coronavirus species. cache = ./cache/cord-279979-3ecnbqom.txt txt = ./txt/cord-279979-3ecnbqom.txt === reduce.pl bib === id = cord-341858-uz7vqq3r author = Davis, C. Todd title = Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness date = 2014-12-12 pages = extension = .txt mime = text/plain words = 4133 sentences = 163 flesch = 31 summary = Influenza virus GOF studies have focused on several research areas: in vitro and/or in vivo replication in mammalian cell culture or animal hosts, adaptive mutations conferring changes in host susceptibility, alteration of receptor binding profiles and/or tropism for mammalian airway tissues, enhanced polymerase activity, changes in host antiviral response (e.g., cell signaling pathways), susceptibility to antiviral drugs, and pathogenesis and/or transmissibility in mammalian animal models. In both instances, molecularly based surveillance identified naturally occurring mutations in avian influenza viruses isolated from humans that had been demonstrated by GOF studies to increase transmissibility in the ferret model, prompting the public health actions described below. At the same time that increased case numbers were detected, public sequence database mining by researchers identified viruses from several 2013 human infections that possessed the same mutations shown by GOF studies to alter receptor-binding specificity toward an ␣2,6 preference (K189R and Q222L) and enhanced respiratory droplet transmission of a clade 1 virus in ferrets (N220K with Q222L) (42) . cache = ./cache/cord-341858-uz7vqq3r.txt txt = ./txt/cord-341858-uz7vqq3r.txt === reduce.pl bib === id = cord-290297-efo9f7c5 author = Vaillancourt, Mylene title = The Unrecognized Threat of Secondary Bacterial Infections with COVID-19 date = 2020-08-07 pages = extension = .txt mime = text/plain words = 1354 sentences = 72 flesch = 37 summary = In recent studies on COVID-19 patients, secondary bacterial infections were significantly associated with worse outcomes and death despite antimicrobial therapies. In the past, the intensive use of antibiotics during the severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic led to increases in the prevalence of multidrug-resistant bacteria. T he outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the greatest pandemic of our generation, with 16 million people infected and 650,000 deaths worldwide so far (1) . In a multicenter study that included 476 COVID-19 patients, secondary bacterial infections were significantly associated with outcome severity (2) . During the first SARS-CoV outbreak in 2003, up to 30% of patients were diagnosed with secondary bacterial infections and coinfection was positively associated with disease severity (5, 6) . Increase in methicillin-resistant Staphylococcus aureus acquisition rate and change in pathogen pattern associated with an outbreak of severe acute respiratory syndrome cache = ./cache/cord-290297-efo9f7c5.txt txt = ./txt/cord-290297-efo9f7c5.txt === reduce.pl bib === id = cord-001672-7lh8iqm1 author = Klotz, Lynn C. title = Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory date = 2015-04-14 pages = extension = .txt mime = text/plain words = 1348 sentences = 80 flesch = 63 summary = I n a Letter to the Editor of mBio, Professor Ron Fouchier published a calculation (1) in which he finds a very low probability, P 1 , for a laboratory-acquired infection (LAI) for a single lab for a single year. Fouchier uses a simplistic formula, y ϭ 1/P 1 , to calculate the elapsed time in years for an LAI to escape from his laboratory, y ϭ 1/(1 ϫ 10 -6 ) ϭ 1 ϫ 10 6 , that is, the million years stated in his Letter. I suggest attaching little weight to this elapsed time calculation and instead concentrating on risk ϭ likelihood ϫ consequences, starting with the P 1 probability, specifically: potential pandemic fatalities ϭ (probability of a community LAI) ϫ (probability that the community LAI leads to a pandemic) ϫ (estimated fatalities in a pandemic). My risk calculation estimates the likelihood of a community LAI for both a single laboratory and n laboratories conducting this research over y years. cache = ./cache/cord-001672-7lh8iqm1.txt txt = ./txt/cord-001672-7lh8iqm1.txt === reduce.pl bib === id = cord-274399-cd7cmpoj author = Barzin, Amir title = SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date = 2020-09-29 pages = extension = .txt mime = text/plain words = 3304 sentences = 189 flesch = 47 summary = This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This study identifies a very limited seroprevalence of SARS-CoV-2 among asymptomatic individuals accessing the UNC Health system. This study employed an EUA assay performed in a CLIA-certified laboratory on a venous blood sample, with demonstrated specificity to detect antibodies only to SARS-CoV-2, not to seasonal coronaviruses. Upon arrival for SARS-CoV-2 Seroprevalence in North Carolina ® routine care or scheduled visits for enrollment into the study, patients performed a consent procedure that included reviewing recent COVID-19 clinical history using UNC IRB-approved questionnaires. cache = ./cache/cord-274399-cd7cmpoj.txt txt = ./txt/cord-274399-cd7cmpoj.txt === reduce.pl bib === id = cord-348131-pkovyjo6 author = Li, Yize title = Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling date = 2019-11-12 pages = extension = .txt mime = text/plain words = 7680 sentences = 421 flesch = 60 summary = The mRNA level of RNase L did not change upon IFN treatment in RoNi/7 cells, indicating that, similarly to the human RNASEL gene, bat RNASEL is not an ISG ( Fig. 2A) , consistent with the lack of an ISRE in its promoter region (data not shown). Upon infection with SINV, degradation of rRNA, as assessed by Bioanalyzer, was detected in wild-type (WT) and bOAS1-KO and bOAS2-KO cells but not in bOAS3-KO and bRNase L-KO cells (Fig. 6C) , indicating that the activation of RNase L during SINV infection in RoNi/7 cells is dependent on bOAS3 expression, similar to our previous findings in human cells. bOASL2 shares high sequence similarity with mouse OASL2 (see Fig. S2 in the supplemental material), suggesting that Activation of Bat RNase L Depends on OAS3 but Not MAVS ® like the mouse protein, bOASL2 may have catalytic activity. cache = ./cache/cord-348131-pkovyjo6.txt txt = ./txt/cord-348131-pkovyjo6.txt === reduce.pl bib === id = cord-305336-wxiazglk author = Li, Ji Lian title = Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera date = 2014-01-21 pages = extension = .txt mime = text/plain words = 6907 sentences = 319 flesch = 50 summary = In the present study, we showed that a plant-pathogenic RNA virus, tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees, Apis mellifera, resulting in infections that were found throughout the entire body. While intracellular life cycle, species-level genetic variation, and pathogenesis of the virus in honeybee hosts remain to be determined, the increasing prevalence of TRSV in conjunction with other bee viruses from spring toward winter in infected colonies was associated with gradual decline of host populations and winter colony collapse, suggesting the negative impact of the virus on colony survival. Conventional RT-PCR was performed on RNA samples extracted from adult bees, Varroa mites, different tissues, and bee bread collected from the same colony for the presence and distribution of TRSV. cache = ./cache/cord-305336-wxiazglk.txt txt = ./txt/cord-305336-wxiazglk.txt === reduce.pl bib === id = cord-292742-mio4przi author = McAloose, Denise title = From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date = 2020-10-13 pages = extension = .txt mime = text/plain words = 6364 sentences = 309 flesch = 47 summary = KEYWORDS One Health, Panthera leo, Panthera tigris, SARS-CoV-2, in situ hybridization, lion, rRT-PCR, tiger, virus isolation, whole-genome sequencing, zoo, zoonotic infection C oronaviruses are a recognized cause of disease in humans and animals (1) . Subsequent to confirmation of SARS-CoV-2 infection in the animals, an epidemiologic investigation of zoo staff identified 10 zoo keepers and two managers who provided care for and had close (Յ1.8-m) but not direct contact with the tigers or lions between 16 March 2020 (the date on which the zoo was closed to the public due to the pandemic) and 27 March to 3 April 2020 (timeline of disease onset in the animals). Nine complete SARS-CoV-2 genome sequences (from four tigers, three lions, and two keepers) and eight full-length S gene sequences (from seven symptomatic animals and one asymptomatic animal) were generated directly from respiratory and/or fecal samples (Data Sets 3 and 4). cache = ./cache/cord-292742-mio4przi.txt txt = ./txt/cord-292742-mio4przi.txt === reduce.pl bib === id = cord-351482-hzh5tyoo author = Peng, Xinxia title = Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection date = 2011-11-15 pages = extension = .txt mime = text/plain words = 7697 sentences = 348 flesch = 49 summary = The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. In total, of 4,473,273 start positions in the genome with at least one uniquely mapped read, we found that about 5% (233,236) gave at least 4 reads of the same length in a sample, resulting in 16,054 nonredundant candidate loci for putative small RNAs. About 1.7% (276/16,054) of the candidate loci (median length, 39 nt) were differentially expressed during SARS-CoV and/or influenza virus infection (see Table S2 and Fig. S4a in the supplemental material); 46 of those candidate loci overlapped with annotated miRNA precursors (miRBase version 16). cache = ./cache/cord-351482-hzh5tyoo.txt txt = ./txt/cord-351482-hzh5tyoo.txt === reduce.pl bib === id = cord-339269-7m53i1h9 author = Pope, Welkin H. title = Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood date = 2014-12-02 pages = extension = .txt mime = text/plain words = 5517 sentences = 246 flesch = 51 summary = smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. Proteomic analysis using mass spectrometry provides evidence for expression of at least 83 Patience proteins, two of which are from cryptic open reading frames (ORFs) embedded within annotated genes. Genome annotation of Patience indicates that all open reading frames and one tRNA gene are transcribed in the same direction ( Fig. 5 ; Table 1 ). A similar scenario is seen within Patience gene 20, where two peptides corresponding to a 171-bp open reading frame on the same strand were identified with high confidence (see Fig. S1B in the supplemental material). Their codon usage profiles (see Fig. S6 in the supplemental material) more closely reflect those of the lower-GC mycobacteriophages such as Patience. cache = ./cache/cord-339269-7m53i1h9.txt txt = ./txt/cord-339269-7m53i1h9.txt === reduce.pl bib === id = cord-324978-9qfhsj3n author = Alagaili, Abdulaziz N. title = Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date = 2014-02-25 pages = extension = .txt mime = text/plain words = 3565 sentences = 165 flesch = 53 summary = The presence of viral nucleic acids in rectal and nasal swabs and a subset of serum and whole blood samples was assayed by reverse transcriptionquantitative PCR (RT-qPCR) with primers targeting the upE and ORF1a genome regions of MERS-CoV (16, 17) . Rectal and nasal swabs collected in parallel with serum samples from the same animals were assayed for MERS-CoV nucleic acids by RT-qPCR. PCR analysis of a random selection of serum and whole blood samples collected from nasal or rectal swab PCR-positive, seropositive, and seronegative DC revealed no evidence of viremia (see Table S1 in the supplemental material). Definitive evidence that DC can be infected with MERS-CoV was obtained when viral sequences were detected in nasal swabs from DC sampled in close proximity to outbreaks of the disease among humans in Qatar (11) and Jeddah, KSA (10) . cache = ./cache/cord-324978-9qfhsj3n.txt txt = ./txt/cord-324978-9qfhsj3n.txt === reduce.pl bib === id = cord-335938-hscgmis5 author = Gralinski, Lisa E. title = Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury date = 2013-08-06 pages = extension = .txt mime = text/plain words = 7816 sentences = 370 flesch = 42 summary = The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. To model system-wide behaviors following SARS-CoV infection, we performed a dose-response study that included biological sampling at multiple time points, transcriptional and proteomic systems biology data, and mathematical modeling algorithms to identify signaling networks associated with progression from severe to lethal disease outcomes. These data demonstrate the successful use of highly refined modeling algorithms to identify and validate novel genes and pathways that play critical roles in SARS-CoV pathogenesis and the development of ALI following virus infection in the lung. Similar changes in the urokinase, coagulation, and fibrinolysin pathway expression signatures are noted following highly pathogenic SARS-CoV and influenza virus infections (see Fig. S5B and S6 in the supplemental material), arguing for a con-served role for these pathways in virus-induced end-stage lung diseases, like ALI and ARDS. cache = ./cache/cord-335938-hscgmis5.txt txt = ./txt/cord-335938-hscgmis5.txt === reduce.pl bib === id = cord-352096-cc3dzycl author = Richman, Douglas D. title = Antiviral Drug Discovery To Address the COVID-19 Pandemic date = 2020-09-25 pages = extension = .txt mime = text/plain words = 1520 sentences = 70 flesch = 35 summary = Regardless of whether or when a vaccine becomes available, antivirals for SARS-CoV-2 will still be needed for several reasons: the unlikelihood that a vaccine will be 100% effective, the incompleteness of vaccine coverage because of both vaccine hesitancy and the numerous logistical challenges to accomplishing prompt large-scale immunization of the majority of the population, the possibility of limited durability of vaccine protection, the need for additional prophylaxis for high-risk subjects and poor vaccine responders, and the future value of effective antiviral treatment for Middle East respiratory syndrome (MERS) and new coronaviruses that will likely emerge from zoonoses. suggest that the purported activity against SARS-CoV-2 of the two HIV protease inhibitors, lopinavir and nelfinavir, is probably attributable to cellular toxicity. Structurebased design of antiviral drug candidates targeting the SARS-CoV-2 main protease AT-527 is a potent in vitro replication inhibitor of SARS-CoV-2, the virus responsible for the COVID-19 pandemic cache = ./cache/cord-352096-cc3dzycl.txt txt = ./txt/cord-352096-cc3dzycl.txt === reduce.pl bib === id = cord-295946-p9enjxiq author = Hattori, Shin-ichiro title = GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection date = 2020-08-20 pages = extension = .txt mime = text/plain words = 7044 sentences = 390 flesch = 54 summary = We assessed various newly generated compounds that target the main protease (M(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various previously known compounds reportedly active against SARS-CoV-2, employing RNA quantitative PCR (RNA-qPCR), cytopathicity assays, and immunocytochemistry. When VeroE6 cells were exposed to SARS-CoV-2 WK-521 at a multiplicity of infection (MOI) of 0.05 and cultured in the presence of various concentrations of the two indole chloropyridinyl esters GRL-0820 and GRL-0920, the compounds were found to be highly potent against SARS-CoV-2 WK-521 with 50% effective concentration (EC 50 ) values of 15 Ϯ 18 and 2.8 Ϯ 0.3 M, respectively, using RNA-qPCR (Table 1) . When VeroE6 TMPRSS2 cells were exposed to SARS-CoV-2 WK-521 and cultured in the presence of various concentrations of lopinavir and nelfinavir, many virus-infected cells were seen at 1 and 10 M and stained in green, indicating that these two compounds had no detectable antiviral activity in the assay. cache = ./cache/cord-295946-p9enjxiq.txt txt = ./txt/cord-295946-p9enjxiq.txt === reduce.pl bib === === reduce.pl bib === id = cord-331361-pd9lt4n2 author = Mathieu, Cyrille title = Heparan Sulfate-Dependent Enhancement of Henipavirus Infection date = 2015-03-10 pages = extension = .txt mime = text/plain words = 5837 sentences = 291 flesch = 49 summary = Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Strikingly, heparin was also active when applied after contact with the virus, and both pretreatment and posttreatment with heparin were effective in inhibiting human PBL-mediated trans-infection of either NiV or HeV (Fig. 2B ). Heparin treatment modestly, but significantly, reduced the percentage of infected cells from both cell lines, indicating that this molecule may also directly inhibit or delay the binding of NiV to its entry receptors EFN-B2 and -B3. Nipah virus (isolate UMMC1; Gen-Bank accession number AY029767) (42), recombinant NiV expressing enhanced green fluorescent protein (45) , and Hendra virus (Australia/ horse/1994) obtained from Porton Down Laboratory, United Kingdom, were prepared on Vero-E6 cells as described previously (46) , and infection virus was used in the INSERM Jean Mérieux BSL4 laboratory in Lyon, France. cache = ./cache/cord-331361-pd9lt4n2.txt txt = ./txt/cord-331361-pd9lt4n2.txt === reduce.pl bib === id = cord-350603-ssen3q08 author = Albrecht, Randy A. title = Moving Forward: Recent Developments for the Ferret Biomedical Research Model date = 2018-07-17 pages = extension = .txt mime = text/plain words = 1607 sentences = 80 flesch = 37 summary = While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. To resolve this, a group of researchers from around the world are working together to develop validated reagents and assays to improve our understanding of the innate and adaptive immune responses in the ferret. Flow Cytometric and cytokine ELISPOT approaches to characterize the cell-mediated immune response in ferrets following influenza virus Infection Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection Infection of ferrets with influenza virus elicits a light chain-biased antibody response against hemagglutinin Ferrets as a novel animal model for studying human respiratory syncytial virus infections in immunocompetent and immunocompromised hosts A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute Nipah virus infection cache = ./cache/cord-350603-ssen3q08.txt txt = ./txt/cord-350603-ssen3q08.txt === reduce.pl bib === id = cord-356325-gk5jve0i author = Beaudoin-Bussières, Guillaume title = Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals date = 2020-10-16 pages = extension = .txt mime = text/plain words = 2143 sentences = 120 flesch = 50 summary = Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. Of note, while we observed enhanced infectivity for the D614G variant compared to its WT SARS-CoV-2 S counterpart (see Fig. S2A in the supplemental material), no major differences in neutralization with convalescent plasma were detected at either time point (Fig. S2B) , thus suggesting that the D614G change does not affect the overall conformation of the Spike, in agreement with recent findings (17, 22) . The capacity to neutralize SARS-CoV-2 S WT-or D614G-pseudotyped particles significantly correlated with the presence of RBD-specific IgG, IgM, IgA, and anti-S antibodies (Fig. S3) . Interestingly, we observed a pronounced (20% to 30%) decrease in the proportion of convalescent individuals able to neutralize pseudoparticles bearing SARS-CoV-2 S glycoprotein between 6 and 10 weeks after the onset of symptoms. cache = ./cache/cord-356325-gk5jve0i.txt txt = ./txt/cord-356325-gk5jve0i.txt ===== Reducing email addresses Creating transaction Updating adr table ===== Reducing keywords cord-001152-v6uc0ijw cord-292883-7hvq9qaj cord-001450-7vsdqhi0 cord-001527-x8yswoua cord-256970-b8czrq29 cord-260087-9o9tb28h cord-287487-qeltdch7 cord-327660-p1b07b4t cord-003143-n6b0r92e cord-252671-uf96jgig cord-297082-2rhoffx2 cord-286587-x0wqtlxh cord-004469-m2fwefuy cord-003092-3owcqt3d cord-305698-fjd0rsrf cord-274396-l611eisi cord-279979-3ecnbqom cord-298773-vnmc6nqd cord-001528-33f94doo cord-278303-lnrgom58 cord-263357-krvei97r cord-003609-p0ydzjre cord-002467-b0p1b4g8 cord-326160-mf0vh6iu cord-303915-14yfs4pa cord-001672-7lh8iqm1 cord-337492-o6sy4zi4 cord-353612-9ux181xg cord-296028-hqrd1e8p cord-335432-9aszklx3 cord-281389-sht0yx4a cord-308848-chvvtr0d cord-274663-zyzgk2z3 cord-289360-h6wvx7gw cord-348669-mizygp4j cord-303262-grrd6jmt cord-256550-72i1x02f cord-330315-upcf15q5 cord-334463-nvu5tqxb cord-287892-bnqmwst8 cord-290297-efo9f7c5 cord-305336-wxiazglk cord-001223-6sb3ipab cord-264050-6zpw6itb cord-274399-cd7cmpoj cord-348131-pkovyjo6 cord-280001-y7pvj2l1 cord-344227-rdlinzrn cord-331361-pd9lt4n2 cord-351482-hzh5tyoo cord-324978-9qfhsj3n cord-292742-mio4przi cord-295946-p9enjxiq cord-273391-vmtfn78x cord-335938-hscgmis5 cord-352096-cc3dzycl cord-341858-uz7vqq3r cord-339269-7m53i1h9 cord-350603-ssen3q08 cord-356325-gk5jve0i cord-012487-s920s5wb cord-001340-kqcx7lrq Creating transaction Updating wrd table ===== Reducing urls cord-001450-7vsdqhi0 cord-001223-6sb3ipab cord-001152-v6uc0ijw cord-003143-n6b0r92e cord-003609-p0ydzjre cord-305698-fjd0rsrf cord-256970-b8czrq29 cord-274396-l611eisi cord-298773-vnmc6nqd cord-012487-s920s5wb cord-281389-sht0yx4a cord-287487-qeltdch7 cord-278303-lnrgom58 cord-003092-3owcqt3d cord-279979-3ecnbqom cord-353612-9ux181xg cord-327660-p1b07b4t cord-326160-mf0vh6iu cord-002467-b0p1b4g8 cord-348131-pkovyjo6 cord-289360-h6wvx7gw cord-287892-bnqmwst8 cord-351482-hzh5tyoo cord-274663-zyzgk2z3 cord-350603-ssen3q08 cord-292742-mio4przi cord-295946-p9enjxiq cord-324978-9qfhsj3n cord-264050-6zpw6itb cord-335938-hscgmis5 cord-339269-7m53i1h9 cord-344227-rdlinzrn cord-280001-y7pvj2l1 cord-334463-nvu5tqxb Creating transaction Updating url table ===== Reducing named entities cord-001223-6sb3ipab cord-274396-l611eisi cord-286587-x0wqtlxh cord-001528-33f94doo cord-281389-sht0yx4a cord-278303-lnrgom58 cord-279979-3ecnbqom cord-256970-b8czrq29 cord-305698-fjd0rsrf cord-263357-krvei97r cord-297082-2rhoffx2 cord-001152-v6uc0ijw cord-003092-3owcqt3d cord-002467-b0p1b4g8 cord-003609-p0ydzjre cord-003143-n6b0r92e cord-298773-vnmc6nqd cord-001672-7lh8iqm1 cord-001340-kqcx7lrq cord-001527-x8yswoua cord-001450-7vsdqhi0 cord-303915-14yfs4pa cord-260087-9o9tb28h cord-252671-uf96jgig cord-004469-m2fwefuy cord-330315-upcf15q5 cord-353612-9ux181xg cord-287487-qeltdch7 cord-337492-o6sy4zi4 cord-335432-9aszklx3 cord-327660-p1b07b4t cord-012487-s920s5wb cord-292883-7hvq9qaj cord-326160-mf0vh6iu cord-296028-hqrd1e8p cord-256550-72i1x02f cord-348669-mizygp4j cord-287892-bnqmwst8 cord-344227-rdlinzrn cord-331361-pd9lt4n2 cord-290297-efo9f7c5 cord-295946-p9enjxiq cord-274399-cd7cmpoj cord-335938-hscgmis5 cord-334463-nvu5tqxb cord-351482-hzh5tyoo cord-350603-ssen3q08 cord-352096-cc3dzycl cord-305336-wxiazglk cord-348131-pkovyjo6 cord-273391-vmtfn78x cord-303262-grrd6jmt cord-292742-mio4przi cord-356325-gk5jve0i cord-324978-9qfhsj3n cord-341858-uz7vqq3r cord-264050-6zpw6itb cord-289360-h6wvx7gw cord-308848-chvvtr0d cord-280001-y7pvj2l1 cord-339269-7m53i1h9 cord-274663-zyzgk2z3 Creating transaction Updating ent table ===== Reducing parts of speech cord-305698-fjd0rsrf cord-298773-vnmc6nqd cord-263357-krvei97r cord-001152-v6uc0ijw cord-256970-b8czrq29 cord-003092-3owcqt3d cord-292883-7hvq9qaj cord-012487-s920s5wb cord-004469-m2fwefuy cord-001450-7vsdqhi0 cord-001223-6sb3ipab cord-001340-kqcx7lrq cord-274396-l611eisi cord-001527-x8yswoua cord-252671-uf96jgig cord-260087-9o9tb28h cord-286587-x0wqtlxh cord-002467-b0p1b4g8 cord-287487-qeltdch7 cord-296028-hqrd1e8p cord-003143-n6b0r92e cord-001528-33f94doo cord-001672-7lh8iqm1 cord-297082-2rhoffx2 cord-281389-sht0yx4a cord-278303-lnrgom58 cord-303915-14yfs4pa cord-335432-9aszklx3 cord-274663-zyzgk2z3 cord-256550-72i1x02f cord-330315-upcf15q5 cord-308848-chvvtr0d cord-353612-9ux181xg cord-303262-grrd6jmt cord-348669-mizygp4j cord-273391-vmtfn78x cord-003609-p0ydzjre cord-290297-efo9f7c5 cord-264050-6zpw6itb cord-341858-uz7vqq3r cord-331361-pd9lt4n2 cord-344227-rdlinzrn cord-337492-o6sy4zi4 cord-287892-bnqmwst8 cord-348131-pkovyjo6 cord-305336-wxiazglk cord-351482-hzh5tyoo cord-326160-mf0vh6iu cord-274399-cd7cmpoj cord-324978-9qfhsj3n cord-289360-h6wvx7gw cord-350603-ssen3q08 cord-356325-gk5jve0i cord-334463-nvu5tqxb cord-295946-p9enjxiq cord-292742-mio4przi cord-339269-7m53i1h9 cord-352096-cc3dzycl cord-279979-3ecnbqom cord-280001-y7pvj2l1 cord-335938-hscgmis5 cord-327660-p1b07b4t Creating transaction Updating pos table Building ./etc/reader.txt cord-327660-p1b07b4t cord-287487-qeltdch7 cord-003609-p0ydzjre cord-273391-vmtfn78x cord-003143-n6b0r92e cord-326160-mf0vh6iu number of items: 62 sum of words: 306,988 average size in words: 5,032 average readability score: 47 nouns: virus; cells; infection; viruses; protein; cell; expression; influenza; mice; analysis; data; host; genes; gene; proteins; coronavirus; replication; genome; response; disease; samples; activity; levels; time; type; study; membrane; receptor; results; lung; sequence; studies; syndrome; transmission; sequences; °; research; antibody; responses; culture; vaccine; number; infections; rnas; assay; patients; mouse; material; activation; model verbs: using; showed; infect; including; increased; suggest; binding; indicate; induced; expressed; associated; identified; detected; see; follow; providing; performed; observing; containing; determine; describing; find; based; mediated; compared; generate; requires; reduced; known; treated; result; inhibit; report; demonstrated; occur; predicted; confirmed; causing; analyzing; collected; testing; represent; derived; regulate; obtained; encodes; revealed; remained; targeted; isolated adjectives: viral; human; respiratory; small; specific; immune; clinical; high; different; acute; severe; antiviral; anti; similar; novel; supplemental; potential; like; infected; infectious; important; low; several; many; new; significant; positive; cellular; single; multiple; genomic; present; large; molecular; higher; dependent; functional; negative; wild; recombinant; pathogenic; full; first; early; additional; genetic; lower; consistent; available; critical adverbs: also; however; previously; well; highly; significantly; respectively; therefore; directly; likely; even; first; together; recently; strongly; specifically; rather; prior; interestingly; furthermore; indeed; finally; closely; still; often; much; alone; less; similarly; differentially; relatively; least; approximately; double; subsequently; generally; currently; notably; especially; almost; rapidly; moreover; importantly; completely; clearly; already; overnight; additionally; primarily; briefly pronouns: we; it; our; their; its; they; i; his; us; them; my; he; itself; me; one; themselves; your; you; ourselves; nsp4; mine; her; y499; y322; nsp15; nsp10; hmgl; him; -luc proper nouns: Fig; SARS; RNA; CoV; CoV-2; MERS; M; PKR; T; PCR; H5N1; C; CD47; IFN-; GP; HCoV; S; EMC; hpi; PBS; NSP4; MHV; HN; H7N9; N; F; L; RNase; Table; WT; HIV-1; Vero; HIV; S1; E.; A; RT; East; ϩ; Middle; PEDV; MAV-1; HA; miRNAs; ⌬; S2; SINV; RdRp; S.; H1N1 keywords: sars; rna; virus; mers; h5n1; h7n9; gof; covid-19; cov-2; small; sinv; pcr; function; fouchier; emc; cell; Ϫrna; Ϫ/Ϫ; wk-521; viroporin; viral; varroa; vaccine; unc; trsv; tiger; st209; spr; smq; sjr; sirp; sfb; serpine1; sequence; saa; rbd; predict; ppp; pkr; piv5-mers; piv5; pfu; pedv; pdf-2180; pc22a; pbs; pause; patience; p250; orf3-rfp one topic; one dimension: virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950510/ titles(s): Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1 three topics; one dimension: cells; cells; virus file(s): https://www.ncbi.nlm.nih.gov/pubmed/30482837/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479006/, https://doi.org/10.1128/mbio.00826-17 titles(s): Origins and Evolution of the Global RNA Virome | Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) | Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases five topics; three dimensions: cells virus rna; cells virus pkr; cov sars virus; virus viruses influenza; cells virus infection file(s): https://www.ncbi.nlm.nih.gov/pubmed/30482837/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030562/, https://doi.org/10.1128/mbio.00271-13, https://doi.org/10.1128/mbio.00826-17, https://www.ncbi.nlm.nih.gov/pubmed/27406561/ titles(s): Origins and Evolution of the Global RNA Virome | Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation | Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury | Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases | Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins Type: cord title: journal-mbio-cord date: 2021-05-30 time: 16:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"mBio" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-324978-9qfhsj3n author: Alagaili, Abdulaziz N. title: Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date: 2014-02-25 words: 3565.0 sentences: 165.0 pages: flesch: 53.0 cache: ./cache/cord-324978-9qfhsj3n.txt txt: ./txt/cord-324978-9qfhsj3n.txt summary: The presence of viral nucleic acids in rectal and nasal swabs and a subset of serum and whole blood samples was assayed by reverse transcriptionquantitative PCR (RT-qPCR) with primers targeting the upE and ORF1a genome regions of MERS-CoV (16, 17) . Rectal and nasal swabs collected in parallel with serum samples from the same animals were assayed for MERS-CoV nucleic acids by RT-qPCR. PCR analysis of a random selection of serum and whole blood samples collected from nasal or rectal swab PCR-positive, seropositive, and seronegative DC revealed no evidence of viremia (see Table S1 in the supplemental material). Definitive evidence that DC can be infected with MERS-CoV was obtained when viral sequences were detected in nasal swabs from DC sampled in close proximity to outbreaks of the disease among humans in Qatar (11) and Jeddah, KSA (10) . abstract: The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats. url: https://doi.org/10.1128/mbio.00884-14 doi: 10.1128/mbio.00884-14 id: cord-350603-ssen3q08 author: Albrecht, Randy A. title: Moving Forward: Recent Developments for the Ferret Biomedical Research Model date: 2018-07-17 words: 1607.0 sentences: 80.0 pages: flesch: 37.0 cache: ./cache/cord-350603-ssen3q08.txt txt: ./txt/cord-350603-ssen3q08.txt summary: While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. To resolve this, a group of researchers from around the world are working together to develop validated reagents and assays to improve our understanding of the innate and adaptive immune responses in the ferret. Flow Cytometric and cytokine ELISPOT approaches to characterize the cell-mediated immune response in ferrets following influenza virus Infection Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection Infection of ferrets with influenza virus elicits a light chain-biased antibody response against hemagglutinin Ferrets as a novel animal model for studying human respiratory syncytial virus infections in immunocompetent and immunocompromised hosts A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute Nipah virus infection abstract: Since the initial report in 1911, the domestic ferret has become an invaluable biomedical research model. While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. However, there are limitations to the model that must be overcome for maximal utility for the scientific community. Here, we describe important recent advances that will accelerate biomedical research with this animal model. url: https://doi.org/10.1128/mbio.01113-18 doi: 10.1128/mbio.01113-18 id: cord-303915-14yfs4pa author: Almazán, Fernando title: Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate date: 2013-09-10 words: 7132.0 sentences: 336.0 pages: flesch: 50.0 cache: ./cache/cord-303915-14yfs4pa.txt txt: ./txt/cord-303915-14yfs4pa.txt summary: The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. Using this clone, recombinant MERS-CoV (rMERS-CoV) deletion mutants were constructed lacking genes nonessential for virus replication. An infectious cDNA clone was assembled as a BAC under the control of the cytomegalovirus (CMV) immediate-early pro-moter, based on the genome sequence of the MERS-CoV-EMC12 strain (GenBank accession number JX869059) (15) . Based on published data showing that the deletion of CoV E protein resulted in either replication-competent, propagation-defective viruses (24) or attenuated viruses (25, 26, 31) , a cDNA clone with the E gene deleted (pBAC-MERS-⌬E) was constructed from pBAC-MERS FL . abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. Following transfection with the cDNA clone, infectious virus was rescued in both Vero A66 and Huh-7 cells. Recombinant MERS-CoVs (rMERS-CoVs) lacking the accessory genes 3, 4a, 4b, and 5 were successfully rescued from cDNA clones with these genes deleted. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. In contrast, an engineered mutant virus lacking the structural E protein (rMERS-CoV-ΔE) was not successfully rescued, since viral infectivity was lost at early passages. Interestingly, the rMERS-CoV-ΔE genome replicated after cDNA clone was transfected into cells. The infectious virus was rescued and propagated in cells expressing the E protein in trans, indicating that this virus was replication competent and propagation defective. Therefore, the rMERS-CoV-ΔE mutant virus is potentially a safe and promising vaccine candidate to prevent MERS-CoV infection. IMPORTANCE Since the emergence of MERS-CoV in the Arabian Peninsula during the summer of 2012, it has already spread to 10 different countries, infecting around 94 persons and showing a mortality rate higher than 50%. This article describes the development of the first reverse genetics system for MERS-CoV, based on the construction of an infectious cDNA clone inserted into a bacterial artificial chromosome. Using this system, a collection of rMERS-CoV deletion mutants has been generated. Interestingly, one of the mutants with the E gene deleted was a replication-competent, propagation-defective virus that could only be grown in the laboratory by providing E protein in trans, whereas it would only survive a single virus infection cycle in vivo. This virus constitutes a vaccine candidate that may represent a balance between safety and efficacy for the induction of mucosal immunity, which is needed to prevent MERS-CoV infection. url: https://doi.org/10.1128/mbio.00650-13 doi: 10.1128/mbio.00650-13 id: cord-279979-3ecnbqom author: Anthony, S. J. title: Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus date: 2017-04-04 words: 5345.0 sentences: 247.0 pages: flesch: 48.0 cache: ./cache/cord-279979-3ecnbqom.txt txt: ./txt/cord-279979-3ecnbqom.txt summary: Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Predicting the interactions of virus binding domains with a particular host receptor (for example, the human MERS-CoV receptor DPP4) is possible through the use of structural modeling and the generation of infectious clones. This virus (PREDICT/PDF-2180) shares the same putative S1 subunit recombination that was observed in NeoCoV, allowing us to also consider whether the spike recombination was critical for the emergence of MERS-CoV in humans. Based on the current criteria for species demarcation established by the International Committee for the Taxonomy of Viruses (Ͼ90% amino acid sequence identity in the replicase proteins), PREDICT/PDF-2180 shares sufficient genetic identity to MERS-CoV to be considered a member of the MERS-like Coronavirus species. abstract: The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans. url: https://www.ncbi.nlm.nih.gov/pubmed/28377531/ doi: 10.1128/mbio.00373-17 id: cord-337492-o6sy4zi4 author: Baric, Ralph S. title: Next-Generation High-Throughput Functional Annotation of Microbial Genomes date: 2016-10-04 words: 3026.0 sentences: 144.0 pages: flesch: 34.0 cache: ./cache/cord-337492-o6sy4zi4.txt txt: ./txt/cord-337492-o6sy4zi4.txt summary: The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community. Unlike large-scale genome-sequencing or structural-genomics efforts, the functional annotation of uncharacterized genes is not well developed technologically, and therefore, the scientific community cannot rely on a well-defined, mature set of experimental approaches. The NIAID has implemented a program aimed at assigning functions to open reading frames (ORFs) and small noncoding RNAs (ncRNAs) that have been discovered by large-scale sequencing efforts to begin addressing this gap in our understanding of bacterial and viral gene function. abstract: Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community. url: https://doi.org/10.1128/mbio.01245-16 doi: 10.1128/mbio.01245-16 id: cord-274399-cd7cmpoj author: Barzin, Amir title: SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date: 2020-09-29 words: 3304.0 sentences: 189.0 pages: flesch: 47.0 cache: ./cache/cord-274399-cd7cmpoj.txt txt: ./txt/cord-274399-cd7cmpoj.txt summary: This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This study identifies a very limited seroprevalence of SARS-CoV-2 among asymptomatic individuals accessing the UNC Health system. This study employed an EUA assay performed in a CLIA-certified laboratory on a venous blood sample, with demonstrated specificity to detect antibodies only to SARS-CoV-2, not to seasonal coronaviruses. Upon arrival for SARS-CoV-2 Seroprevalence in North Carolina ® routine care or scheduled visits for enrollment into the study, patients performed a consent procedure that included reviewing recent COVID-19 clinical history using UNC IRB-approved questionnaires. abstract: Characterizing the asymptomatic spread of SARS-CoV-2 is important for understanding the COVID-19 pandemic. This study was aimed at determining asymptomatic spread of SARS-CoV-2 in a suburban, Southern U.S. population during a period of state restrictions and physical distancing mandates. This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. To estimate point seroprevalence of SARS-CoV-2 among asymptomatic individuals over time, two cohort studies were examined. The first cohort study, named ScreenNC, was comprised of outpatient clinics, and the second cohort study, named ScreenNC2, was comprised of inpatients unrelated to COVID-19. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This assay as performed under CLIA had a reported specificity/sensitivity of 100%/99.6%. ScreenNC identified 24 out of 2,973 (0.8%) positive individuals among asymptomatic participants accessing health care during 28 April to 19 June 2020, which was increasing over time. A separate cohort, ScreenNC2, sampled from 3 March to 4 June 2020, identified 10 out of 1,449 (0.7%) positive participants. url: https://doi.org/10.1128/mbio.02426-20 doi: 10.1128/mbio.02426-20 id: cord-348669-mizygp4j author: Beall, Anne title: Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A date: 2016-01-05 words: 6021.0 sentences: 293.0 pages: flesch: 43.0 cache: ./cache/cord-348669-mizygp4j.txt txt: ./txt/cord-348669-mizygp4j.txt summary: title: Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. While the recombinant icPEDV replicated the clinical phenotypes of parental PC22A in vivo, icPEDV-⌬ORF3-RFP infection resulted in a partial attenuation in pigs based on lower diarrhea scores. Both the parental PEDV PC22A strain and its derivative recombinant cloned virus were genetically stable and fully pathogenic in neonatal gnotobiotic pigs, demonstrating that icPEDV provides not only a strategy that allows for the systematic evaluation of the role of viral genes in pathogenesis, tropism, and virulence but also a translational platform for the development of rationally attenuated live virus vaccines. abstract: Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic alphacoronavirus. In the United States, highly virulent PEDV strains cause between 80 and 100% mortality in suckling piglets and are rapidly transmitted between animals and farms. To study the genetic factors that regulate pathogenesis and transmission, we developed a molecular clone of PEDV strain PC22A. The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. Using reverse genetics, we removed open reading frame 3 (ORF3) and replaced this region with a red fluorescent protein (RFP) gene to generate icPEDV-ΔORF3-RFP. icPEDV-ΔORF3-RFP replicated efficiently in vitro and in vivo, was efficiently transmitted among pigs, and produced lethal disease outcomes. However, the diarrheic scores in icPEDV-ΔORF3-RFP-infected pigs were lower than those in wild-type-virus- or icPEDV-infected pigs, and the virus formed smaller plaques than those of PC22A. Together, these data describe the development of a robust reverse-genetics platform for identifying genetic factors that regulate pathogenic outcomes and transmission efficiency in vivo, providing key infrastructural developments for developing and evaluating the efficacy of live attenuated vaccines and therapeutics in a clinical setting. url: https://doi.org/10.1128/mbio.01451-15 doi: 10.1128/mbio.01451-15 id: cord-356325-gk5jve0i author: Beaudoin-Bussières, Guillaume title: Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals date: 2020-10-16 words: 2143.0 sentences: 120.0 pages: flesch: 50.0 cache: ./cache/cord-356325-gk5jve0i.txt txt: ./txt/cord-356325-gk5jve0i.txt summary: Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. Of note, while we observed enhanced infectivity for the D614G variant compared to its WT SARS-CoV-2 S counterpart (see Fig. S2A in the supplemental material), no major differences in neutralization with convalescent plasma were detected at either time point (Fig. S2B) , thus suggesting that the D614G change does not affect the overall conformation of the Spike, in agreement with recent findings (17, 22) . The capacity to neutralize SARS-CoV-2 S WT-or D614G-pseudotyped particles significantly correlated with the presence of RBD-specific IgG, IgM, IgA, and anti-S antibodies (Fig. S3) . Interestingly, we observed a pronounced (20% to 30%) decrease in the proportion of convalescent individuals able to neutralize pseudoparticles bearing SARS-CoV-2 S glycoprotein between 6 and 10 weeks after the onset of symptoms. abstract: In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms. url: https://www.ncbi.nlm.nih.gov/pubmed/33067385/ doi: 10.1128/mbio.02590-20 id: cord-278303-lnrgom58 author: Björnsdóttir, Sigríður title: Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases date: 2017-08-01 words: 6243.0 sentences: 305.0 pages: flesch: 51.0 cache: ./cache/cord-278303-lnrgom58.txt txt: ./txt/cord-278303-lnrgom58.txt summary: This study represents the first time that whole-genome sequencing has been used to investigate an epidemic on a national scale to identify the likely causative agent and the link to an associated zoonotic infection. This isolation of the population has meant that Icelandic horses have remained free from most common contagious diseases of Equidae, including equine influenza, equine rhinopneumonitis, equine viral arteritis, Rhodococcus equi infection, and strangles (Streptococcus equi subsp. Removal of strains with identical sequences that were recovered from the same animal on the same date produced a data set of 59 ST209 isolates with 434 polymorphic core genome positions (Table S2 ). zooepidemicus recovered from Icelandic horses in this study are also likely to have caused clinical signs of disease. zooepidemicus likely persisted in the horses at the Icelandic Veterinary Institute, accruing nucleotide diversity over time within this isolated population. abstract: Iceland is free of the major infectious diseases of horses. However, in 2010 an epidemic of respiratory disease of unknown cause spread through the country’s native horse population of 77,000. Microbiological investigations ruled out known viral agents but identified the opportunistic pathogen Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) in diseased animals. We sequenced the genomes of 257 isolates of S. zooepidemicus to differentiate epidemic from endemic strains. We found that although multiple endemic clones of S. zooepidemicus were present, one particular clone, sequence type 209 (ST209), was likely to have been responsible for the epidemic. Concurrent with the epidemic, ST209 was also recovered from a human case of septicemia, highlighting the pathogenic potential of this strain. Epidemiological investigation revealed that the incursion of this strain into one training yard during February 2010 provided a nidus for the infection of multiple horses that then transmitted the strain to farms throughout Iceland. This study represents the first time that whole-genome sequencing has been used to investigate an epidemic on a national scale to identify the likely causative agent and the link to an associated zoonotic infection. Our data highlight the importance of national biosecurity to protect vulnerable populations of animals and also demonstrate the potential impact of S. zooepidemicus transmission to other animals, including humans. url: https://doi.org/10.1128/mbio.00826-17 doi: 10.1128/mbio.00826-17 id: cord-001450-7vsdqhi0 author: Burgess, Stacey L. title: Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis date: 2014-11-04 words: 3996.0 sentences: 208.0 pages: flesch: 42.0 cache: ./cache/cord-001450-7vsdqhi0.txt txt: ./txt/cord-001450-7vsdqhi0.txt summary: title: Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. It is also quite possible that mediators induced by the intestinal microbiota in the serum might influence the bone marrow in such a way as to prime DCs to provide protection against, or exacerbate, enteropathogen infections (27, 28) . histolytica colitis and that bone marrow dendritic cells (BM-DCs) derived from SFB-colonized mice were able to recapitulate protection in mice that had not been colonized with the bacteria. These data suggest that intestinal colonization with a commensal bacterium can alter bone marrow in such a way as to provide protection against parasite infection. Thus, as SFB increased frequency of intestinal DCs, IL-23, IL-17A expression, and circulating serum SAA, we examined the capacity of bone marrow DCs from SFB-infected mice to produce IL-23 in response to trophozoites. abstract: There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(−) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222101/ doi: 10.1128/mbio.01817-14 id: cord-274663-zyzgk2z3 author: Chang, Stewart T. title: Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4(+) T Cell Line date: 2011-09-20 words: 6991.0 sentences: 358.0 pages: flesch: 48.0 cache: ./cache/cord-274663-zyzgk2z3.txt txt: ./txt/cord-274663-zyzgk2z3.txt summary: Using NGS, we detected small but significant changes in host gene expression affecting T cell function that coincided with the initiation of viral RNA production at 12 h postinfection (hpi). In addition, by using NGS, we observed the dramatic expansion of viral mRNA expression and detected new viral splice events occurring during viral replication and differential expression of noncoding RNA species, including microRNA host genes. In our data set, we observed no change in the expression of the Crm1-encoding gene XPO1, but several members of the Ran signaling pathway were downregulated, suggesting that the overall export of unspliced viral RNA was suppressed (see Fig. S5B in the supplemental material; data not shown for XPO1). The regulation of these and transcription factors specific for other functions (e.g., EGR1, KLF13, and MYC) may explain how HIV initiated replication with minimal disruption to host gene expression at 12 hpi but elicited larger-scale changes later in infection. abstract: Next-generation sequencing (NGS) enables the highly sensitive measurement of whole transcriptomes. We report the first application to our knowledge of this technology to the analysis of RNA from a CD4(+) T cell line infected with intact HIV. We sequenced the total mRNA from infected cells and detected differences in the expression of both host and viral mRNA. Viral reads represented a large portion of the total mapped sequencing reads: approximately 20% at 12 h postinfection (hpi) and 40% at 24 hpi. We also detected a small but significant suppression of T cell activation-related genes at 12 hpi. This suppression persisted and expanded by 24 hpi, providing new possible markers of virus-induced T cell cytopathology. By 24 hpi, the expression of over 50% of detectable host loci was also altered, indicating widespread alteration of host processes, including RNA processing, splicing, and transport to an extent not previously reported. In addition, next-generation sequencing provided insights into alternative viral RNA splice events and the expression of noncoding RNAs, including microRNA host genes. url: https://www.ncbi.nlm.nih.gov/pubmed/21933919/ doi: 10.1128/mbio.00134-11 id: cord-341858-uz7vqq3r author: Davis, C. Todd title: Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness date: 2014-12-12 words: 4133.0 sentences: 163.0 pages: flesch: 31.0 cache: ./cache/cord-341858-uz7vqq3r.txt txt: ./txt/cord-341858-uz7vqq3r.txt summary: Influenza virus GOF studies have focused on several research areas: in vitro and/or in vivo replication in mammalian cell culture or animal hosts, adaptive mutations conferring changes in host susceptibility, alteration of receptor binding profiles and/or tropism for mammalian airway tissues, enhanced polymerase activity, changes in host antiviral response (e.g., cell signaling pathways), susceptibility to antiviral drugs, and pathogenesis and/or transmissibility in mammalian animal models. In both instances, molecularly based surveillance identified naturally occurring mutations in avian influenza viruses isolated from humans that had been demonstrated by GOF studies to increase transmissibility in the ferret model, prompting the public health actions described below. At the same time that increased case numbers were detected, public sequence database mining by researchers identified viruses from several 2013 human infections that possessed the same mutations shown by GOF studies to alter receptor-binding specificity toward an ␣2,6 preference (K189R and Q222L) and enhanced respiratory droplet transmission of a clade 1 virus in ferrets (N220K with Q222L) (42) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25505125/ doi: 10.1128/mbio.02431-14 id: cord-335432-9aszklx3 author: Duprex, W. Paul title: Falling down the Rabbit Hole: aTRIP Toward Lexiconic Precision in the “Gain-of-Function” Debate date: 2014-12-12 words: 2438.0 sentences: 122.0 pages: flesch: 50.0 cache: ./cache/cord-335432-9aszklx3.txt txt: ./txt/cord-335432-9aszklx3.txt summary: (B) Dual-use research of concern (DURC) is a small subset of DUR involving life sciences research that, based on current understanding, can reasonably be anticipated to provide knowledge, information, products, or technologies that could be directly misapplied, posing a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. (D) Although spanning all of microbiological research, much of the DURC debate has focused on virology, where selection processes of circulating and synthetically generated agents have been used to enhance transmission. For some, gain of function causes the most concern, although even for the influenza transmission studies, it is simplistic to focus on only one phenotype/ one function as a range or on infectivity changed during selection of mammal-adapted avian influenza viruses. Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion abstract: nan url: https://doi.org/10.1128/mbio.02421-14 doi: 10.1128/mbio.02421-14 id: cord-286587-x0wqtlxh author: Fedson, David S. title: Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection date: 2020-03-20 words: 1052.0 sentences: 72.0 pages: flesch: 49.0 cache: ./cache/cord-286587-x0wqtlxh.txt txt: ./txt/cord-286587-x0wqtlxh.txt summary: Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection. We believe that investigators in China and elsewhere should undertake studies of patients with severe COVID-19 infection to determine whether targeting the host response with widely available and inexpensive generic drugs, like ARBs and statins, will improve their chances of survival. Convincing evidence of the effectiveness of this treatment would suggest a syndromic approach to treating patients with other emerging infectious diseases, like Ebola and pandemic influenza, as well as everyday illnesses, like sepsis and pneumonia (19) . Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola Treating the host response to Ebola virus disease with generic statins and angiotensin receptor blockers abstract: Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection. url: https://doi.org/10.1128/mbio.00398-20 doi: 10.1128/mbio.00398-20 id: cord-308848-chvvtr0d author: Fidel, Paul L. title: Reply to Özdemir, “Measles-Mumps-Rubella Vaccine and COVID-19 Relationship” date: 2020-09-22 words: 558.0 sentences: 33.0 pages: flesch: 52.0 cache: ./cache/cord-308848-chvvtr0d.txt txt: ./txt/cord-308848-chvvtr0d.txt summary: While the current clinical trials are not investigating this issue directly, we have focused on the MMR vaccine as it is widely available and has the potential for any or all of the three components to induce the MDSCs. However, based on our data in the animal model of fungal/bacterial sepsis, very strong long-lasting protection is afforded from one administration of the attenuated fungal isolate (7) . Finally, while it is true that we do not know how long the trained innate immunity persists, the randomized clinical trial of MMR versus placebo in health care workers and the nonhuman primate study that will test MMR or BCG in a model of COVID-19 infection will go far to answer these questions. To date, the trained innate response with BCG suggests the immunity is functional for approximately 1 year based on infant vaccinations (8) . Immune protection against lethal fungal-bacterial intra-abdominal infections abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32963010/ doi: 10.1128/mbio.02465-20 id: cord-001528-33f94doo author: Fouchier, Ron A. M. title: Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited date: 2015-01-23 words: 3522.0 sentences: 141.0 pages: flesch: 40.0 cache: ./cache/cord-001528-33f94doo.txt txt: ./txt/cord-001528-33f94doo.txt summary: Initial calculations of the potential risks associated with research on influenza virus transmission via respiratory droplets or aerosols between ferrets (1-4) used reports on select agent theft, loss, and release collected by the U.S. Centers for Disease Control and Prevention (CDC) from 2004 to 2010 (7) to calculate the probability of occurrence of LAIs. Although these reports have limitations (1, 4, 7) , they provide the most recent account of LAIs in the United States and probably reflect the current state of the art in biosafety and biosecurity practices better than older studies on laboratory incidents (8, 9) , e.g., as a consequence of the implementation of the U.S. select agent program and best practices developed in biosafety and biosecurity in general over the last decades. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323420/ doi: 10.1128/mbio.02560-14 id: cord-260087-9o9tb28h author: Furmanski, Martin title: The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards date: 2015-09-29 words: 648.0 sentences: 34.0 pages: flesch: 45.0 cache: ./cache/cord-260087-9o9tb28h.txt txt: ./txt/cord-260087-9o9tb28h.txt summary: R ozo and Gronvall, in "The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate" (1), confirmed the laboratory origin of the 1977 influenza pandemic and judged it was unintentional, but they concluded that its "relevance to GoF research is greatly diminished if the 1977 epidemic was the result of a vaccine trial or vaccine development gone awry; these are both more plausible explanations than a single laboratory accident." Rozo and Gronvall also stated that, "in 1977, influenza research was performed without modern biosafety regulations and protective equipment, making the lab accident hypothesis much less relevant to the modern GoF debate." However, the current record of containment of high-consequence pathogens is hardly reassuring. Activities at the select agent laboratory at the Tulane National Primate Research Center remain suspended after Burkholderia pseudomallei, the agent of melioidosis, escaped containment and caused multiple primate infections in an outdoor primate facility (5, 6) . abstract: nan url: https://doi.org/10.1128/mbio.01434-15 doi: 10.1128/mbio.01434-15 id: cord-001152-v6uc0ijw author: Girardi, Erika title: Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells date: 2013-11-19 words: 7021.0 sentences: 383.0 pages: flesch: 52.0 cache: ./cache/cord-001152-v6uc0ijw.txt txt: ./txt/cord-001152-v6uc0ijw.txt summary: Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21to 28-nucleotide (nt) species during infection. We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs. Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability. The identification of small RNAs from RNA viruses could be seen either as a result of a productive mechanism for the pathogen (as for virus-encoded miRNAs) or as the consequence of a host response to control the infection by degrading viral RNAs. SINV expresses four enzymes that play key functions during the viral replicative cycle. abstract: Small RNAs play a critical role in host-pathogen interaction. Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity. Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has not been clearly proven in higher vertebrates. However, it is well established that their response to viral infection relies on the recognition of viral RNAs by host pattern recognition receptors (PRRs) to trigger activation of the interferon pathway. In the present work, we report the existence of a novel small noncoding RNA population produced in mammalian cells upon RNA virus infection. Using Sindbis virus (SINV) as a prototypic arbovirus model, we profiled the small RNA population of infected cells in both human and African green monkey cell lines. Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21- to 28-nucleotide (nt) species during infection. We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs. Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability. Altogether, our findings show that stable modified small viral RNAs could represent a novel way to modulate host-virus interaction upon SINV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870239/ doi: 10.1128/mbio.00698-13 id: cord-003609-p0ydzjre author: Goodman, Danielle E. title: Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date: 2019-04-23 words: 8894.0 sentences: 487.0 pages: flesch: 55.0 cache: ./cache/cord-003609-p0ydzjre.txt txt: ./txt/cord-003609-p0ydzjre.txt summary: RNA was purified from fractions containing monosomes MAV-1 Degrades PKR during Infection ® and polysomes and then used to generate cDNA, which we assayed for PKR mRNA by qPCR (Fig. 4C) . Thus, the 18-hpi time point is considered an early time point during MAV-1 infection of CMT93 cells, prior to DNA replication, suggesting the involvement of an early viral protein in PKR depletion. We examined PKR protein levels during MAV-1 infection and found that PKR was depleted from the cells as early as 12 hpi (Fig. 7) . While the PKR mRNAs in C57BL/6 MEFs were depleted 33% at 48 hpi and 40% at 72 hpi compared to mock-infected lysates, this was not sufficient to explain the 84% and 94% reductions, respectively, in PKR protein levels at those time points (Fig. 2B ). abstract: Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479006/ doi: 10.1128/mbio.00668-19 id: cord-287487-qeltdch7 author: Graepel, Kevin W. title: Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations date: 2017-11-07 words: 7470.0 sentences: 467.0 pages: flesch: 49.0 cache: ./cache/cord-287487-qeltdch7.txt txt: ./txt/cord-287487-qeltdch7.txt summary: Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. High-or low-fidelity variants are described for many RNA viruses infecting animals, including the coronaviruses (CoVs) murine hepatitis virus (MHV-A59) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) (13) (14) (15) (16) (17) , as well as foot-and-mouth disease virus (18) (19) (20) (21) (22) , poliovirus (23) (24) (25) (26) (27) (28) (29) , Chikungunya virus (30, 31) , influenza virus (32) , coxsackievirus B3 (33, 34) , and human enterovirus 71 (35) (36) (37) . The evolved mutations in MHV-ExoN(-) nsp14 and nsp12, which encodes the RdRp, accounted for only part of the increased nucleoside analogue resistance of MHV-ExoN(-) P250, implicating multiple replicase proteins in adaptation for viral fitness. abstract: The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3′-to-5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication. url: https://www.ncbi.nlm.nih.gov/pubmed/29114026/ doi: 10.1128/mbio.01503-17 id: cord-335938-hscgmis5 author: Gralinski, Lisa E. title: Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury date: 2013-08-06 words: 7816.0 sentences: 370.0 pages: flesch: 42.0 cache: ./cache/cord-335938-hscgmis5.txt txt: ./txt/cord-335938-hscgmis5.txt summary: The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. To model system-wide behaviors following SARS-CoV infection, we performed a dose-response study that included biological sampling at multiple time points, transcriptional and proteomic systems biology data, and mathematical modeling algorithms to identify signaling networks associated with progression from severe to lethal disease outcomes. These data demonstrate the successful use of highly refined modeling algorithms to identify and validate novel genes and pathways that play critical roles in SARS-CoV pathogenesis and the development of ALI following virus infection in the lung. Similar changes in the urokinase, coagulation, and fibrinolysin pathway expression signatures are noted following highly pathogenic SARS-CoV and influenza virus infections (see Fig. S5B and S6 in the supplemental material), arguing for a con-served role for these pathways in virus-induced end-stage lung diseases, like ALI and ARDS. abstract: Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. url: https://doi.org/10.1128/mbio.00271-13 doi: 10.1128/mbio.00271-13 id: cord-344227-rdlinzrn author: Gralinski, Lisa E. title: Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis date: 2018-10-09 words: 6557.0 sentences: 309.0 pages: flesch: 43.0 cache: ./cache/cord-344227-rdlinzrn.txt txt: ./txt/cord-344227-rdlinzrn.txt summary: As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Mice deficient in C3 (C3 -/-), the central protein of the complement signaling pathway, were protected from SARS-CoV-induced weight loss and had reduced pathology, improved respiratory function, and lower levels of inflammatory cytokines/chemokines in the lung and periphery. Immunohistochemical staining revealed that SARS-CoV MA15 infection induced complement deposition in the lung (Fig. 4) , similar to that associated with pathogenesis in Ross River virus-infected mice (41) and some influenza virus infections (34) , and it is likely that complement deposition contributes to pulmonary disease and inflammatory cell recruitment. abstract: Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3(–/–)), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3(–/–) mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3(–/–) mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3(–/–) mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic. url: https://doi.org/10.1128/mbio.01753-18 doi: 10.1128/mbio.01753-18 id: cord-295946-p9enjxiq author: Hattori, Shin-ichiro title: GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection date: 2020-08-20 words: 7044.0 sentences: 390.0 pages: flesch: 54.0 cache: ./cache/cord-295946-p9enjxiq.txt txt: ./txt/cord-295946-p9enjxiq.txt summary: We assessed various newly generated compounds that target the main protease (M(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various previously known compounds reportedly active against SARS-CoV-2, employing RNA quantitative PCR (RNA-qPCR), cytopathicity assays, and immunocytochemistry. When VeroE6 cells were exposed to SARS-CoV-2 WK-521 at a multiplicity of infection (MOI) of 0.05 and cultured in the presence of various concentrations of the two indole chloropyridinyl esters GRL-0820 and GRL-0920, the compounds were found to be highly potent against SARS-CoV-2 WK-521 with 50% effective concentration (EC 50 ) values of 15 Ϯ 18 and 2.8 Ϯ 0.3 M, respectively, using RNA-qPCR (Table 1) . When VeroE6 TMPRSS2 cells were exposed to SARS-CoV-2 WK-521 and cultured in the presence of various concentrations of lopinavir and nelfinavir, many virus-infected cells were seen at 1 and 10 M and stained in green, indicating that these two compounds had no detectable antiviral activity in the assay. abstract: We assessed various newly generated compounds that target the main protease (M(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various previously known compounds reportedly active against SARS-CoV-2, employing RNA quantitative PCR (RNA-qPCR), cytopathicity assays, and immunocytochemistry. Here, we show that two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, exerted potent activity against SARS-CoV-2 in cell-based assays performed using VeroE6 cells and TMPRSS2-overexpressing VeroE6 cells. While GRL-0820 and the nucleotide analog remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred. No significant anti-SARS-CoV-2 activity was found for several compounds reportedly active against SARS-CoV-2 such as lopinavir, nelfinavir, nitazoxanide, favipiravir, and hydroxychroloquine. In contrast, GRL-0920 exerted potent activity against SARS-CoV-2 (50% effective concentration [EC(50)] = 2.8 μM) and dramatically reduced the infectivity, replication, and cytopathic effect of SARS-CoV-2 without significant toxicity as examined with immunocytochemistry. Structural modeling shows that indole and chloropyridinyl of the derivatives interact with two catalytic dyad residues of M(pro), Cys145 and His41, resulting in covalent bonding, which was verified using high-performance liquid chromatography–mass spectrometry (HPLC/MS), suggesting that the indole moiety is critical for the anti-SARS-CoV-2 activity of the derivatives. GRL-0920 might serve as a potential therapeutic for coronavirus disease 2019 (COVID-19) and might be optimized to generate more-potent anti-SARS-CoV-2 compounds. url: https://doi.org/10.1128/mbio.01833-20 doi: 10.1128/mbio.01833-20 id: cord-263357-krvei97r author: Holmes, Kathryn V. title: The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia date: 2013-01-08 words: 2076.0 sentences: 83.0 pages: flesch: 43.0 cache: ./cache/cord-263357-krvei97r.txt txt: ./txt/cord-263357-krvei97r.txt summary: Sequencing and bioinformatic analysis of the viral genomic RNA showed that it is a novel virus not previously detected in any other species and that its closest relatives are two Asian bat coronaviruses. demonstrated how state-of-the-art sequencing technology and bioinformatic analysis can quickly provide critical insight into the viral genome sequence, phylogeny, replication strategy, and potential drug and vaccine targets and generate tools to evaluate the possible epidemic risk associated with this novel human virus. In June 2012, a novel coronavirus, tentatively named HCoV-EMC (for Erasmus Medical Center where the initial genome sequence was done), was isolated in a monkey kidney cell line from a sputum specimen from a 60-year-old man from the Kingdom of Saudi Arabia who died of acute severe pneumonia and renal failure. The genomic analysis suggests that HCoV-EMC may be a zoonotic virus that spilled over to infect the 9 laboratory confirmed patients, either directly or indirectly, from an unknown reservoir, possibly a bat. abstract: A new human betacoronavirus in lineage c, tentatively called HCoV-EMC, was isolated from a patient from the Kingdom of Saudi Arabia who died from acute severe pneumonia and renal failure. The viral RNA has been detected in eight additional cases. Sequencing and bioinformatic analysis of the viral genomic RNA showed that it is a novel virus not previously detected in any other species and that its closest relatives are two Asian bat coronaviruses. HCoV-EMC may represent a sporadic spillover to humans from an unknown animal reservoir. In a recent article, van Boheemen et al. demonstrated how state-of-the-art sequencing technology and bioinformatic analysis can quickly provide critical insight into the viral genome sequence, phylogeny, replication strategy, and potential drug and vaccine targets and generate tools to evaluate the possible epidemic risk associated with this novel human virus. url: https://www.ncbi.nlm.nih.gov/pubmed/23300251/ doi: 10.1128/mbio.00548-12 id: cord-287892-bnqmwst8 author: Hyser, Joseph M. title: Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity date: 2010-11-30 words: 7093.0 sentences: 397.0 pages: flesch: 49.0 cache: ./cache/cord-287892-bnqmwst8.txt txt: ./txt/cord-287892-bnqmwst8.txt summary: The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. We previously showed that NSP4 forms a novel vesicular compartment concomitantly with increased [Ca 2ϩ ]cyto (45) and that these structures associate with the autophagy protein LC3 and surround viroplasms, cytoplasmic inclusions in rotavirus-infected cells that support virus replication. abstract: Many viruses alter intracellular calcium homeostasis. The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. However, the NSP4 domain and mechanism that increases [Ca(2+)]cyto are unknown. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. Mutational analysis showed that NSP4 viroporin activity was mediated by an amphipathic α-helical domain downstream of a conserved lysine cluster. The lysine cluster directed integral membrane insertion of the viroporin domain and was critical for viroporin activity. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. When [Ca(2+)]cyto was increased pharmacologically with thapsigargin, viroporin mutants formed puncta, showing that elevation of calcium levels and puncta formation are distinct functions of NSP4 and indicating that NSP4 directly or indirectly responds to elevated cytoplasmic calcium levels. NSP4 viroporin activity establishes the mechanism for NSP4-mediated elevation of [Ca(2+)]cyto, a critical event that regulates rotavirus replication and virion assembly. url: https://doi.org/10.1128/mbio.00265-10 doi: 10.1128/mbio.00265-10 id: cord-256970-b8czrq29 author: Ielasi, Francesco S. title: Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins date: 2016-07-12 words: 9315.0 sentences: 446.0 pages: flesch: 46.0 cache: ./cache/cord-256970-b8czrq29.txt txt: ./txt/cord-256970-b8czrq29.txt summary: We first associated each edge with a relevance depending on the type of its connecting nodes (i.e., protein-glycan) according to the proposed weights (see equations 1 to 3 in the supplemental material) as a function of the lectin binding intensity measured via glycan array screenings. The hierarchical view (see Fig. 1 , 3, and 7) allowed linking of the experimentally determined lectin specificities (i.e., the glycan determinants) with the potential receptors (human or viral glycoproteins) and then linking of these glycoproteins to cell types/tissues and body systems. The LGI network of Candida Als and Epa adhesins N-Als1p has been shown to interact with fucose-containing glycans that are present in blood group antigens and preferentially with antigen H type 2 (22) . abstract: The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity. url: https://www.ncbi.nlm.nih.gov/pubmed/27406561/ doi: 10.1128/mbio.00584-16 id: cord-003092-3owcqt3d author: Iketani, Sho title: Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation date: 2018-07-03 words: 8948.0 sentences: 392.0 pages: flesch: 46.0 cache: ./cache/cord-003092-3owcqt3d.txt txt: ./txt/cord-003092-3owcqt3d.txt summary: These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses. Deep genomic sequencing of nine sets of paired clinical samples (primary nasal swabs in viral transport medium) and culture isolates (culture harvest from zero passage virus) led to discovery of a number of HN mutations associated with rapid evolution in culture. To assess the frequency of mutations identified earlier, we also performed deep sequencing of 118 HPIV-3 clinical samples and culture isolates from the University of Washington Virology Laboratory, allowing us to confirm that the alterations associated with brief exposure to culture for viral isolation were almost entirely found in the sequences of culture isolates and found commonly within populations of viruses in those isolates. abstract: Human parainfluenza viruses cause a large burden of human respiratory illness. While much research relies upon viruses grown in cultured immortalized cells, human parainfluenza virus 3 (HPIV-3) evolves in culture. Cultured viruses differ in their properties compared to clinical strains. We present a genome-wide survey of HPIV-3 adaptations to culture using metagenomic next-generation sequencing of matched pairs of clinical samples and primary culture isolates (zero passage virus). Nonsynonymous changes arose during primary viral isolation, almost entirely in the genes encoding the two surface glycoproteins—the receptor binding protein hemagglutinin-neuraminidase (HN) or the fusion protein (F). We recovered genomes from 95 HPIV-3 primary culture isolates and 23 HPIV-3 strains directly from clinical samples. HN mutations arising during primary viral isolation resulted in substitutions at HN’s dimerization/F-interaction site, a site critical for activation of viral fusion. Alterations in HN dimer interface residues known to favor infection in culture occurred within 4 days (H552 and N556). A novel cluster of residues at a different face of the HN dimer interface emerged (P241 and R242) and imply a role in HPIV-3-mediated fusion. Functional characterization of these culture-associated HN mutations in a clinical isolate background revealed acquisition of the fusogenic phenotype associated with cultured HPIV-3; the HN-F complex showed enhanced fusion and decreased receptor-cleaving activity. These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030562/ doi: 10.1128/mbio.00898-18 id: cord-289360-h6wvx7gw author: Imperiale, Michael J. title: The Importance of Virology at a Time of Great Need and Great Jeopardy date: 2015-03-10 words: 1290.0 sentences: 59.0 pages: flesch: 51.0 cache: ./cache/cord-289360-h6wvx7gw.txt txt: ./txt/cord-289360-h6wvx7gw.txt summary: journal: mBio Viruses account for up to 20% of all human cancers, and although a large percentage of new human papillomavirus (HPV) and HBV infections can now be prevented by vaccination, many are already infected, and the vaccines are not being used to their full potential. The tremendous reduction in mortality from such diseases as variola, measles, and rubella came about only because the causative viruses were identified, cultivated, attenuated, and made into effective vaccines by biomedical research. While we scientists cannot directly control funding or regulations, we can take charge of some aspects of the research enterprise in a way to ensure that it continues to benefit society. This requires engaging our elected officials both directly and indirectly by continuing to educate them and the public at large about the importance of fundamental research in infectious diseases. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25759503/ doi: 10.1128/mbio.00236-15 id: cord-305698-fjd0rsrf author: Imperiale, Michael J. title: Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus date: 2014-12-12 words: 1528.0 sentences: 79.0 pages: flesch: 51.0 cache: ./cache/cord-305698-fjd0rsrf.txt txt: ./txt/cord-305698-fjd0rsrf.txt summary: title: Vagueness and Costs of the Pause on Gain-of-Function (GOF) Experiments on Pathogens with Pandemic Potential, Including Influenza Virus We have numerous concerns with this third stoppage, including the timing of the announcement relative to the ongoing debate, the vagueness in the wording of the statement, and the potential effects on the fields of influenza virus and coronavirus research. Second, we worry about the meaning of "reasonably anticipated." Obviously this phrase is very subjective, and similar wording in the definition of dual use research of concern (DURC) has already made assessments of what constitutes DURC very problematic for journals and authors (10) . The current pause affects two dozen studies that include experiments to develop rodent models of coronavirus research (11) . Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25505121/ doi: 10.1128/mbio.02292-14 id: cord-353612-9ux181xg author: Josset, Laurence title: Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus date: 2013-04-30 words: 6299.0 sentences: 303.0 pages: flesch: 49.0 cache: ./cache/cord-353612-9ux181xg.txt txt: ./txt/cord-353612-9ux181xg.txt summary: Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. In addition, several kinase inhibitors (including SB203580, LY294002, and U0126) and a glucocorticoid (dexamethasone) were also predicted to be negative regulators of genes changed similarly after SARS-CoV and HCoV-EMC infection at late times postinfection (see Table S2 in the supplemental material). Importantly, this kinase inhibitor was predicted to regulate genes that were DE similarly by SARS-CoV and HCoV-EMC at late times postinfection (see Table S2 in the supplemental material) and could therefore inhibit both viruses'' replication. abstract: A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. url: https://doi.org/10.1128/mbio.00165-13 doi: 10.1128/mbio.00165-13 id: cord-334463-nvu5tqxb author: Kim, Chonsaeng title: Echovirus 7 Entry into Polarized Intestinal Epithelial Cells Requires Clathrin and Rab7 date: 2012-04-10 words: 6207.0 sentences: 325.0 pages: flesch: 48.0 cache: ./cache/cord-334463-nvu5tqxb.txt txt: ./txt/cord-334463-nvu5tqxb.txt summary: We found that drugs, small interfering RNAs (siRNAs), and dominant negative mutants that target factors required for clathrin-mediated endocytosis, including clathrin and dynamin, inhibited both EV7 infection and internalization of virions from the cell surface. We previously (19) observed that, to infect polarized epithelium, CVB3 binds DAF on the cell surface, moves to the tight junction, and then enters the cell by an unusual mechanism that is independent of both dynamin and clathrin but which requires caveolin; contact with CAR in the tight junction leads to an essential conformational change in the CVB3 virion, but disruption of the capsid does not appear to occur until the virus has moved to an unidentified intracellular compartment. We had previously observed that CVB3 infection of Caco-2 cells occurs by a complex process that depends on caveolin but not dynamin-2, appears to be independent of clathrin-mediated endocytosis, and is inhibited by depletion of membrane cholesterol (19) . abstract: Enteroviruses invade the host by crossing the intestinal mucosa, which is lined by polarized epithelium. A number of enteroviruses, including echoviruses (EV) and group B coxsackieviruses (CVB), initiate infection by attaching to decay-accelerating factor (DAF), a molecule that is highly expressed on the apical surface of polarized epithelial cells. We previously observed that entry of DAF-binding CVB3 into polarized intestinal epithelial cells occurs by an unusual endocytic mechanism that requires caveolin but does not involve clathrin or dynamin. Here we examined the entry of a DAF-binding echovirus, EV7. We found that drugs, small interfering RNAs (siRNAs), and dominant negative mutants that target factors required for clathrin-mediated endocytosis, including clathrin and dynamin, inhibited both EV7 infection and internalization of virions from the cell surface. Once virus had entered the cell, it colocalized with markers of early endosomes (EEA1) and then late endosomes (LAMP-2). Inhibition of endosomal maturation—with siRNAs or dominant negative mutants targeting Rab5 and Rab7—inhibited infection and prevented release of viral RNA into the cell. These results indicate that EV7 is internalized by clathrin-mediated endocytosis and then moves to early and late endosomes before releasing its RNA. Trafficking through endosomes is known to be important for viruses that depend on low pH or endosomal cathepsin proteases to complete the entry process. However, we found that EV7 infection required neither low pH nor cathepsins. url: https://doi.org/10.1128/mbio.00304-11 doi: 10.1128/mbio.00304-11 id: cord-001672-7lh8iqm1 author: Klotz, Lynn C. title: Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory date: 2015-04-14 words: 1348.0 sentences: 80.0 pages: flesch: 63.0 cache: ./cache/cord-001672-7lh8iqm1.txt txt: ./txt/cord-001672-7lh8iqm1.txt summary: I n a Letter to the Editor of mBio, Professor Ron Fouchier published a calculation (1) in which he finds a very low probability, P 1 , for a laboratory-acquired infection (LAI) for a single lab for a single year. Fouchier uses a simplistic formula, y ϭ 1/P 1 , to calculate the elapsed time in years for an LAI to escape from his laboratory, y ϭ 1/(1 ϫ 10 -6 ) ϭ 1 ϫ 10 6 , that is, the million years stated in his Letter. I suggest attaching little weight to this elapsed time calculation and instead concentrating on risk ϭ likelihood ϫ consequences, starting with the P 1 probability, specifically: potential pandemic fatalities ϭ (probability of a community LAI) ϫ (probability that the community LAI leads to a pandemic) ϫ (estimated fatalities in a pandemic). My risk calculation estimates the likelihood of a community LAI for both a single laboratory and n laboratories conducting this research over y years. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453553/ doi: 10.1128/mbio.00268-15 id: cord-256550-72i1x02f author: Klotz, Lynn C. title: Danger of Potential-Pandemic-Pathogen Research Enterprises date: 2015-06-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://doi.org/10.1128/mbio.00815-15 doi: 10.1128/mbio.00815-15 id: cord-001340-kqcx7lrq author: Ladner, Jason T. title: Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing date: 2014-06-17 words: 2512.0 sentences: 121.0 pages: flesch: 40.0 cache: ./cache/cord-001340-kqcx7lrq.txt txt: ./txt/cord-001340-kqcx7lrq.txt summary: Genome sequences play a critical role in our understanding of viral evolution, disease epidemiology, surveillance, diagnosis, and countermeasure development and thus represent valuable resources which must be properly documented and curated to ensure future utility. Here, we outline a set of viral genome quality standards, similar in concept to those proposed for large DNA genomes (4) but focused on the particular challenges of and needs for research on small RNA/ DNA viruses, including characterization of the genomic diversity inherent in all viral samples/populations. Therefore, we have used technology-agnostic criteria to define five standard categories designed to encompass the levels of completeness most often encountered in viral sequencing projects. There is a trend toward requiring a complete genome sequence when a description of a novel virus is being published, and we agree that this is a good goal; however, the amount of time and resources required to complete the last 1 to 2% of a viral genome is often cost and time prohibitive for projects sequencing a large number of samples, and in most cases the very ends of the segments are not essential for proper identification and characterization. abstract: Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five “standard” categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068259/ doi: 10.1128/mbio.01360-14 id: cord-001223-6sb3ipab author: Lennemann, Nicholas J. title: Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1 date: 2014-01-28 words: 5783.0 sentences: 282.0 pages: flesch: 54.0 cache: ./cache/cord-001223-6sb3ipab.txt txt: ./txt/cord-001223-6sb3ipab.txt summary: In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Since complete deglycosylation of the core domains of GP1 did not negatively impact the expression of GP or the transduction of pseudotyped virions, we systematically combined N-linked glycan mutations in the MLD with our 7G mutant. Pseudovirion entry mediated by GP1⌬muc, GP, the 6G mutant, containing a fully deglycosylated glycan cap, and the GPm8G mutant containing a MLD that was fully deglycosylated for N-linked glycans were abrogated by treating Vero cells with the CatB inhibitor CA-074, which profoundly blocked CatB activity (Fig. S4A ). Our findings that deglycosylation of GP pseudovirions enhances the transduction of Vero cells and peritoneal macrophages provides evidence that the N-glycans on GP1 decrease the efficiency of the entry process. abstract: Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950510/ doi: 10.1128/mbio.00862-13 id: cord-002467-b0p1b4g8 author: Leyva-Grado, Victor H. title: Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection date: 2017-03-28 words: 5948.0 sentences: 297.0 pages: flesch: 43.0 cache: ./cache/cord-002467-b0p1b4g8.txt txt: ./txt/cord-002467-b0p1b4g8.txt summary: Similarly, in wild-type mice infected with NL/09 virus, we P2X7 Receptor in Influenza Immunopathology ® observed a significant reduction in body weight at days 4 to 8 postinfection (P Ͻ 0.05) (Fig. 2C) . Reduced virus titers were observed in the lungs of the P2X7r KO mice compared to the wild-type mice, particularly in the samples collected on day 7 postinfection, although these differences were not statistically significant (P ϭ 0.1) (Fig. 3A) . In this study, we showed that mice lacking the purinergic receptor P2X7 have a better clinical outcome after influenza A virus infection characterized by an increased survival rate with an overall reduced immunopathology of the lungs compared to the wild-type mice. Activation of the purinergic receptor P2X7 signaling by increased levels of extracellular ATP caused by influenza virus infection leads to an exacerbated immune response characterized by increased production of proinflammatory cytokines, induction of apoptosis, increased influx of neutrophils in the airways, and development of lung histopathology. abstract: An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virus-infected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b(+) macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals. Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371412/ doi: 10.1128/mbio.00229-17 id: cord-305336-wxiazglk author: Li, Ji Lian title: Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera date: 2014-01-21 words: 6907.0 sentences: 319.0 pages: flesch: 50.0 cache: ./cache/cord-305336-wxiazglk.txt txt: ./txt/cord-305336-wxiazglk.txt summary: In the present study, we showed that a plant-pathogenic RNA virus, tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees, Apis mellifera, resulting in infections that were found throughout the entire body. While intracellular life cycle, species-level genetic variation, and pathogenesis of the virus in honeybee hosts remain to be determined, the increasing prevalence of TRSV in conjunction with other bee viruses from spring toward winter in infected colonies was associated with gradual decline of host populations and winter colony collapse, suggesting the negative impact of the virus on colony survival. Conventional RT-PCR was performed on RNA samples extracted from adult bees, Varroa mites, different tissues, and bee bread collected from the same colony for the presence and distribution of TRSV. abstract: Emerging and reemerging diseases that result from pathogen host shifts are a threat to the health of humans and their domesticates. RNA viruses have extremely high mutation rates and thus represent a significant source of these infectious diseases. In the present study, we showed that a plant-pathogenic RNA virus, tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees, Apis mellifera, resulting in infections that were found throughout the entire body. Additionally, we showed that TRSV-infected individuals were continually present in some monitored colonies. While intracellular life cycle, species-level genetic variation, and pathogenesis of the virus in honeybee hosts remain to be determined, the increasing prevalence of TRSV in conjunction with other bee viruses from spring toward winter in infected colonies was associated with gradual decline of host populations and winter colony collapse, suggesting the negative impact of the virus on colony survival. Furthermore, we showed that TRSV was also found in ectoparasitic Varroa mites that feed on bee hemolymph, but in those instances the virus was restricted to the gastric cecum of Varroa mites, suggesting that Varroa mites may facilitate the spread of TRSV in bees but do not experience systemic invasion. Finally, our phylogenetic analysis revealed that TRSV isolates from bees, bee pollen, and Varroa mites clustered together, forming a monophyletic clade. The tree topology indicated that the TRSVs from arthropod hosts shared a common ancestor with those from plant hosts and subsequently evolved as a distinct lineage after transkingdom host alteration. This study represents a unique example of viruses with host ranges spanning both the plant and animal kingdoms. url: https://www.ncbi.nlm.nih.gov/pubmed/24449751/ doi: 10.1128/mbio.00898-13 id: cord-273391-vmtfn78x author: Li, Kun title: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection date: 2020-04-07 words: 5258.0 sentences: 291.0 pages: flesch: 53.0 cache: ./cache/cord-273391-vmtfn78x.txt txt: ./txt/cord-273391-vmtfn78x.txt summary: title: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. As shown in Fig. 3B to D, we observed a significant increase in the Immunization with PIV5 Expressing MERS-CoV Spike ® percentage and total number of CD8 ϩ -IFN-␥ ϩ cells in the lungs of PIV5-MERS-Simmunized mice in comparison to those infected with PIV5-GFP virus, consistent with a MERS-S-specific primary CD8 T cell response in the lungs. The finding that PIV5 expressing MERS S protected mice against lethal MERS-CoV challenge at a single low dose of 10 4 PFU suggests its potential use as a vaccine vector for emerging viruses such as SARS-CoV-2. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10(4) PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS(MA)6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10(6) PFU UV-inactivated MERS(MA)6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection. url: https://doi.org/10.1128/mbio.00554-20 doi: 10.1128/mbio.00554-20 id: cord-348131-pkovyjo6 author: Li, Yize title: Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling date: 2019-11-12 words: 7680.0 sentences: 421.0 pages: flesch: 60.0 cache: ./cache/cord-348131-pkovyjo6.txt txt: ./txt/cord-348131-pkovyjo6.txt summary: The mRNA level of RNase L did not change upon IFN treatment in RoNi/7 cells, indicating that, similarly to the human RNASEL gene, bat RNASEL is not an ISG ( Fig. 2A) , consistent with the lack of an ISRE in its promoter region (data not shown). Upon infection with SINV, degradation of rRNA, as assessed by Bioanalyzer, was detected in wild-type (WT) and bOAS1-KO and bOAS2-KO cells but not in bOAS3-KO and bRNase L-KO cells (Fig. 6C) , indicating that the activation of RNase L during SINV infection in RoNi/7 cells is dependent on bOAS3 expression, similar to our previous findings in human cells. bOASL2 shares high sequence similarity with mouse OASL2 (see Fig. S2 in the supplemental material), suggesting that Activation of Bat RNase L Depends on OAS3 but Not MAVS ® like the mouse protein, bOASL2 may have catalytic activity. abstract: Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. During infection, OASs, upon sensing double-stranded RNA (dsRNA), produce 2′-5′ oligoadenylates (2-5A), leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Humans encode three active OASs (OAS1 to -3). Analysis of the Egyptian Rousette bat genome combined with mRNA sequencing from bat RoNi/7 cells revealed three homologous OAS proteins. Interferon alpha treatment or viral infection induced all three OAS mRNAs, but RNase L mRNA is constitutively expressed. Sindbis virus (SINV) or vaccinia virus (VACVΔE3L) infection of wild-type (WT) or OAS1-KO (knockout), OAS2-KO, or MAVS-KO RoNi/7 cells, but not RNase L-KO or OAS3-KO cells, induces robust RNase L activation. SINV replication is 100- to 200-fold higher in the absence of RNase L or OAS3 than in WT cells. However, MAVS-KO had no detectable effect on RNA degradation or replication. Thus, in RoNi/7 bat cells, as in human cells, activation of RNase L during infection and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required for the activation of RNase L and restriction of infection. Our findings indicate that OAS proteins serve as pattern recognition receptors (PRRs) to recognize viral dsRNA and that this pathway is a primary response to virus rather than a secondary effect of interferon signaling. url: https://doi.org/10.1128/mbio.02414-19 doi: 10.1128/mbio.02414-19 id: cord-001527-x8yswoua author: Lipsitch, Marc title: Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited” date: 2015-01-23 words: 4673.0 sentences: 205.0 pages: flesch: 45.0 cache: ./cache/cord-001527-x8yswoua.txt txt: ./txt/cord-001527-x8yswoua.txt summary: title: Reply to "Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited" Likewise, Yoshihiro Kawaoka described the purpose of his ferret gain-of-transmission studies as "[t]o determine whether H5N1 viruses could be transmitted between humans" (25) , and the original reports of ferret transmission experiments say that pandemic potential is associated with the changes observed. Fouchier asserts that his claims of the likely low human transmissibility and lethality of the ferret-adapted strains should not be interpreted as reducing the likely benefits of the work for public health. In summary, while the possibility that ferret gain-of-transmission strains are attenuated in humans modestly reduces the risk estimate associated with producing and using them, it may nullify and even reverse the utility of such studies for public health. Studies on influenza virus transmission between ferrets; the public health risks revisited abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323416/ doi: 10.1128/mbio.00041-15 id: cord-331361-pd9lt4n2 author: Mathieu, Cyrille title: Heparan Sulfate-Dependent Enhancement of Henipavirus Infection date: 2015-03-10 words: 5837.0 sentences: 291.0 pages: flesch: 49.0 cache: ./cache/cord-331361-pd9lt4n2.txt txt: ./txt/cord-331361-pd9lt4n2.txt summary: Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Strikingly, heparin was also active when applied after contact with the virus, and both pretreatment and posttreatment with heparin were effective in inhibiting human PBL-mediated trans-infection of either NiV or HeV (Fig. 2B ). Heparin treatment modestly, but significantly, reduced the percentage of infected cells from both cell lines, indicating that this molecule may also directly inhibit or delay the binding of NiV to its entry receptors EFN-B2 and -B3. Nipah virus (isolate UMMC1; Gen-Bank accession number AY029767) (42), recombinant NiV expressing enhanced green fluorescent protein (45) , and Hendra virus (Australia/ horse/1994) obtained from Porton Down Laboratory, United Kingdom, were prepared on Vero-E6 cells as described previously (46) , and infection virus was used in the INSERM Jean Mérieux BSL4 laboratory in Lyon, France. abstract: Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirus trans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cells in vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections. url: https://www.ncbi.nlm.nih.gov/pubmed/25759505/ doi: 10.1128/mbio.02427-14 id: cord-292742-mio4przi author: McAloose, Denise title: From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date: 2020-10-13 words: 6364.0 sentences: 309.0 pages: flesch: 47.0 cache: ./cache/cord-292742-mio4przi.txt txt: ./txt/cord-292742-mio4przi.txt summary: KEYWORDS One Health, Panthera leo, Panthera tigris, SARS-CoV-2, in situ hybridization, lion, rRT-PCR, tiger, virus isolation, whole-genome sequencing, zoo, zoonotic infection C oronaviruses are a recognized cause of disease in humans and animals (1) . Subsequent to confirmation of SARS-CoV-2 infection in the animals, an epidemiologic investigation of zoo staff identified 10 zoo keepers and two managers who provided care for and had close (Յ1.8-m) but not direct contact with the tigers or lions between 16 March 2020 (the date on which the zoo was closed to the public due to the pandemic) and 27 March to 3 April 2020 (timeline of disease onset in the animals). Nine complete SARS-CoV-2 genome sequences (from four tigers, three lions, and two keepers) and eight full-length S gene sequences (from seven symptomatic animals and one asymptomatic animal) were generated directly from respiratory and/or fecal samples (Data Sets 3 and 4). abstract: Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species. url: https://doi.org/10.1128/mbio.02220-20 doi: 10.1128/mbio.02220-20 id: cord-292883-7hvq9qaj author: Nguyen-Contant, Phuong title: S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit date: 2020-09-25 words: 5334.0 sentences: 264.0 pages: flesch: 51.0 cache: ./cache/cord-292883-7hvq9qaj.txt txt: ./txt/cord-292883-7hvq9qaj.txt summary: RBD-binding MBCs sampled in the convalescent phase of SARS-CoV-2 infection expressed Abs with relatively low numbers of V gene mutations, suggesting that this component of the response largely reflected naive B cell activation by novel epitopes (20) . Approximately one-third of non-SARS-CoV-2-exposed subjects in the healthy donor cohort had low levels of serum IgG against the S and N proteins of SARS-CoV-2, likely reflecting cross-reactivity with seasonal HCoVs (Fig. 1A) . Since the healthy donor samples in our analysis were collected 6 to 10 years before the emergence of SARS-CoV-2, we considered the possibility that a recently circulating HCoV was responsible for the higher anti-OC43 S IgG titers in the convalescent subjects. In contrast, IgG MBCs reactive to the S proteins of the HCoVs OC43 and 229E and the control proteins H1 and TTd were detected in nearly 50% or more of non-SARS-CoV-2-exposed subjects, consistent with the higher levels of serum IgG against these antigens (Fig. 2E to H) . abstract: The high susceptibility of humans to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and peripheral blood mononuclear cells (PBMCs) from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBC levels. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG, and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 were higher in convalescent subjects than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane. url: https://www.ncbi.nlm.nih.gov/pubmed/32978311/ doi: 10.1128/mbio.01991-20 id: cord-012487-s920s5wb author: Noga, Marek J. title: Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date: 2020-08-18 words: 7414.0 sentences: 391.0 pages: flesch: 49.0 cache: ./cache/cord-012487-s920s5wb.txt txt: ./txt/cord-012487-s920s5wb.txt summary: By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. In order to understand how the model Gram-negative species Escherichia coli coordinates membrane synthesis with growth, we quantified substrates and enzymes of the fatty acid and PL synthesis pathways under both steady-state and dynamic conditions. The trends in substrate, enzyme, and intermediate concentrations observed in ppGpp-limited cultures are consistent with growth regulating PL flux via posttranslational control-not transcriptional control-of PlsB. To test whether regulation of PlsB activity is sufficient to control steady-state PL synthesis, we constructed a simplified differential equation model that describes fatty acid, LPS initiation, and PL biosynthesis ( Fig. 2A ; see also Text S1 and Table S1 ). abstract: Every cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyzes the committed step of lipopolysaccharide synthesis (LpxC) do not differ across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we found that responses to environmental perturbations are triggered directly via changes in acetyl coenzyme A (acetyl-CoA) concentrations, which enable rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon posttranslational regulation ensures both the reliability and the responsiveness of membrane synthesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439487/ doi: 10.1128/mbio.02703-19 id: cord-330315-upcf15q5 author: Oudshoorn, Diede title: Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication date: 2017-11-21 words: 7718.0 sentences: 349.0 pages: flesch: 50.0 cache: ./cache/cord-330315-upcf15q5.txt txt: ./txt/cord-330315-upcf15q5.txt summary: Using electron tomography, we demonstrate that for both MERS-CoV and SARS-CoV coexpression of nsp3 and nsp4 is required and sufficient to induce DMVs. Coexpression of MERS-CoV nsp3 and nsp4 either as individual proteins or as a self-cleaving nsp3-4 precursor resulted in very similar DMVs, and in both setups we observed proliferation of zippered ER that appeared to wrap into nascent DMVs. Moreover, when inactivating nsp3-4 polyprotein cleavage by mutagenesis, we established that cleavage of the nsp3/nsp4 junction is essential for MERS-CoV DMV formation. To study whether the transmembrane nsp''s of MERS-CoV are able to induce DMV formation, we expressed nsp3 and nsp4 from a CAG promoter (43) either by cotransfection of cells with plasmids encoding individual proteins or by transfection with a single plasmid encoding a self-cleaving nsp3-4 polyprotein fragment ( Fig. 1A ; Table S1 ). The observation of maze-like bodies and circular double-membrane profiles, which were interpreted to represent tubular structures, led these authors to conclude that coexpression of SARS-CoV nsp3 and nsp4 was not sufficient for DMV formation. abstract: Betacoronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), are important pathogens causing potentially lethal infections in humans and animals. Coronavirus RNA synthesis is thought to be associated with replication organelles (ROs) consisting of modified endoplasmic reticulum (ER) membranes. These are transformed into double-membrane vesicles (DMVs) containing viral double-stranded RNA and into other membranous elements such as convoluted membranes, together forming a reticulovesicular network. Previous evidence suggested that the nonstructural proteins (nsp’s) 3, 4, and 6 of the severe acute respiratory syndrome coronavirus (SARS-CoV), which contain transmembrane domains, would all be required for DMV formation. We have now expressed MERS-CoV replicase self-cleaving polyprotein fragments encompassing nsp3-4 or nsp3-6, as well as coexpressed nsp3 and nsp4 of either MERS-CoV or SARS-CoV, to characterize the membrane structures induced. Using electron tomography, we demonstrate that for both MERS-CoV and SARS-CoV coexpression of nsp3 and nsp4 is required and sufficient to induce DMVs. Coexpression of MERS-CoV nsp3 and nsp4 either as individual proteins or as a self-cleaving nsp3-4 precursor resulted in very similar DMVs, and in both setups we observed proliferation of zippered ER that appeared to wrap into nascent DMVs. Moreover, when inactivating nsp3-4 polyprotein cleavage by mutagenesis, we established that cleavage of the nsp3/nsp4 junction is essential for MERS-CoV DMV formation. Addition of the third MERS-CoV transmembrane protein, nsp6, did not noticeably affect DMV formation. These findings provide important insight into the biogenesis of coronavirus DMVs, establish strong similarities with other nidoviruses (specifically, the arteriviruses), and highlight possible general principles in viral DMV formation. url: https://doi.org/10.1128/mbio.01658-17 doi: 10.1128/mbio.01658-17 id: cord-274396-l611eisi author: Park, Su-Jin title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date: 2020-05-22 words: 4355.0 sentences: 208.0 pages: flesch: 46.0 cache: ./cache/cord-274396-l611eisi.txt txt: ./txt/cord-274396-l611eisi.txt summary: While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. In order to determine the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine (HCQ) sulfate, or emtricitabine-tenofovir for treatment of SARS-CoV-2 infection, SARS-CoV-2 antibody-free ferrets (10/group) were inoculated with 10 5.8 50% tissue culture infective doses (TCID 50 )/ml of an NMC-nCoV02 strain through the intranasal (i.n.) route ( Fig. 1 ). Therefore, although clinical symptoms were attenuated in ferret groups treated with antiviral candidates, we also evaluated virus titers in respiratory and gastrointestinal tracts using nasal washes and stool samples, respectively, from SARS-CoV-2-infected ferrets. abstract: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32444382/ doi: 10.1128/mbio.01114-20 id: cord-280001-y7pvj2l1 author: Patel, Robin title: Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19 date: 2020-03-26 words: 1785.0 sentences: 77.0 pages: flesch: 46.0 cache: ./cache/cord-280001-y7pvj2l1.txt txt: ./txt/cord-280001-y7pvj2l1.txt summary: If the test is positive though, the result is most likely correct, although stray viral RNA that makes its way into the testing process (for example, as the specimen is being collected or as a result of specimen cross-contamination or testing performed by a laboratory worker who is infected with SARS-CoV-2 [these are just some examples]) could conceivably result in a falsely positive result. Testing patients for SARS-CoV-2 helps identify those who are infected, which is useful for individual patient management, as well as for implementation of mitigation strategies to prevent spread in health care facilities and in the community alike (Fig. 1) . Given that SARS-CoV-2 can infect anyone and result in transmission prior to the onset of symptoms or even possibly without individuals ever developing symptoms, testing asymptomatic patients could even be considered. Finally, serologic testing can possibly be used diagnostically to test viral RNA-negative individuals presenting late in their illness. abstract: nan url: https://doi.org/10.1128/mbio.00722-20 doi: 10.1128/mbio.00722-20 id: cord-351482-hzh5tyoo author: Peng, Xinxia title: Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection date: 2011-11-15 words: 7697.0 sentences: 348.0 pages: flesch: 49.0 cache: ./cache/cord-351482-hzh5tyoo.txt txt: ./txt/cord-351482-hzh5tyoo.txt summary: The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. In total, of 4,473,273 start positions in the genome with at least one uniquely mapped read, we found that about 5% (233,236) gave at least 4 reads of the same length in a sample, resulting in 16,054 nonredundant candidate loci for putative small RNAs. About 1.7% (276/16,054) of the candidate loci (median length, 39 nt) were differentially expressed during SARS-CoV and/or influenza virus infection (see Table S2 and Fig. S4a in the supplemental material); 46 of those candidate loci overlapped with annotated miRNA precursors (miRBase version 16). abstract: We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection. url: https://www.ncbi.nlm.nih.gov/pubmed/22086488/ doi: 10.1128/mbio.00198-11 id: cord-298773-vnmc6nqd author: Pfeiffer, Julie K. title: Is the Debate and “Pause” on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? date: 2015-01-20 words: 1713.0 sentences: 87.0 pages: flesch: 50.0 cache: ./cache/cord-298773-vnmc6nqd.txt txt: ./txt/cord-298773-vnmc6nqd.txt summary: title: Is the Debate and "Pause" on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? This letter is about the potential impact of the debate and pause on graduate students and postdoctoral fellows and how their future plans may be affected. To gain initial insight into how the debate and research pause have affected trainees, I created an informal survey 2 days before the National Academy of Sciences meeting. These projects involve a subset of "gain of function" experiments designed to create mouse adapted viral strains, generate drug resistant viruses to understand drug mechanisms of action, understand host immunity by analyzing viruses with resistance to certain host immune pathways, and to study factors that influence transmission by the respiratory route (which was made famous by work from the Kawaoka and Fouchier labs in 2012). Third, the debate and research pause are influencing future plans of virology trainees. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25604793/ doi: 10.1128/mbio.02525-14 id: cord-264050-6zpw6itb author: Pirofski, Liise-anne title: Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response date: 2017-12-12 words: 2752.0 sentences: 121.0 pages: flesch: 36.0 cache: ./cache/cord-264050-6zpw6itb.txt txt: ./txt/cord-264050-6zpw6itb.txt summary: The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction. However, the emergence of Cryptococcus gattii in apparently healthy persons in the Pacific Northwest (7) and the unexpected appearance of immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcosis in patients with HIV/AIDS after initiation of antiretroviral therapy (ART) (8, 9) revealed that the host immune response itself can contribute to the pathogenesis of cryptococcosis. The emergence of IRIS-associated cryptococcosis in the setting of ART initiation provided clear evidence that host damage in patients with cryptococcal disease may be driven by inflammation (12) . Chemokine levels and chemokine receptor expression in the blood and the cerebrospinal fluid of HIV-infected patients with cryptococcal meningitis and cryptococcosis-associated immune reconstitution inflammatory syndrome abstract: Cryptococcosis occurs most frequently in immunocompromised individuals. This has led to the prevailing view that this disease is the result of weak immune responses that cannot control the fungus. However, increasingly, clinical and experimental studies have revealed that the host immune response can contribute to cryptococcal pathogenesis, including the recent study of L. M. Neal et al. (mBio 8:e01415-17, 2017, https://doi.org/10.1128/mBio.01415-17) that reports that CD4(+) T cells mediate tissue damage in experimental murine cryptococcosis. This finding has fundamental implications for our understanding of the pathogenesis of cryptococcal disease; it helps explain why immunotherapy has been largely unsuccessful in treatment and provides insight into the paradoxical observation that HIV-associated cryptococcosis may have a better prognosis than cryptococcosis in those with no known immune impairment. The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction. url: https://www.ncbi.nlm.nih.gov/pubmed/29233901/ doi: 10.1128/mbio.02063-17 id: cord-339269-7m53i1h9 author: Pope, Welkin H. title: Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood date: 2014-12-02 words: 5517.0 sentences: 246.0 pages: flesch: 51.0 cache: ./cache/cord-339269-7m53i1h9.txt txt: ./txt/cord-339269-7m53i1h9.txt summary: smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. Proteomic analysis using mass spectrometry provides evidence for expression of at least 83 Patience proteins, two of which are from cryptic open reading frames (ORFs) embedded within annotated genes. Genome annotation of Patience indicates that all open reading frames and one tRNA gene are transcribed in the same direction ( Fig. 5 ; Table 1 ). A similar scenario is seen within Patience gene 20, where two peptides corresponding to a 171-bp open reading frame on the same strand were identified with high confidence (see Fig. S1B in the supplemental material). Their codon usage profiles (see Fig. S6 in the supplemental material) more closely reflect those of the lower-GC mycobacteriophages such as Patience. abstract: Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host. url: https://www.ncbi.nlm.nih.gov/pubmed/25467442/ doi: 10.1128/mbio.02145-14 id: cord-352096-cc3dzycl author: Richman, Douglas D. title: Antiviral Drug Discovery To Address the COVID-19 Pandemic date: 2020-09-25 words: 1520.0 sentences: 70.0 pages: flesch: 35.0 cache: ./cache/cord-352096-cc3dzycl.txt txt: ./txt/cord-352096-cc3dzycl.txt summary: Regardless of whether or when a vaccine becomes available, antivirals for SARS-CoV-2 will still be needed for several reasons: the unlikelihood that a vaccine will be 100% effective, the incompleteness of vaccine coverage because of both vaccine hesitancy and the numerous logistical challenges to accomplishing prompt large-scale immunization of the majority of the population, the possibility of limited durability of vaccine protection, the need for additional prophylaxis for high-risk subjects and poor vaccine responders, and the future value of effective antiviral treatment for Middle East respiratory syndrome (MERS) and new coronaviruses that will likely emerge from zoonoses. suggest that the purported activity against SARS-CoV-2 of the two HIV protease inhibitors, lopinavir and nelfinavir, is probably attributable to cellular toxicity. Structurebased design of antiviral drug candidates targeting the SARS-CoV-2 main protease AT-527 is a potent in vitro replication inhibitor of SARS-CoV-2, the virus responsible for the COVID-19 pandemic abstract: The magnitude of the morbidity and mortality inflicted upon the global population in less than 1 year has driven the inescapable conclusion that the discovery and development of effective antiviral drugs for COVID-19 are urgent and should be prioritized. The antiviral drug discovery programs that emerged for HIV and hepatitis C virus have enabled technology and expertise to accelerate this process for SARS-CoV-2. The description of candidate lead inhibitors for the viral main protease (M(pro)) exemplifies this accelerated approach and reminds us of the needs and opportunities for addressing this pandemic. url: https://doi.org/10.1128/mbio.02134-20 doi: 10.1128/mbio.02134-20 id: cord-004469-m2fwefuy author: Rivera-Hernandez, Tania title: Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies date: 2020-03-10 words: 5219.0 sentences: 267.0 pages: flesch: 44.0 cache: ./cache/cord-004469-m2fwefuy.txt txt: ./txt/cord-004469-m2fwefuy.txt summary: Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. Groups of humanized plasminogen mice were immunized with Combo5 formulated with alum, Advax-2, Advax-4, SWE, LQ, LMQ, or SMQ adjuvant (Table 1) , while negative-control groups were immunized with phosphate-buffered saline (PBS) plus the corresponding adjuvant. Both Advax-2 and Advax-4 induced high antigen-specific antibody titers; however, the rate of survival of vaccinated mice was not significantly higher than that seen with the PBS-adjuvant control groups. Combo5/SMQ immunization resulted in strong secretion of IL-6 and IL-10 and of Th1-type cytokines IFN-␥ and TNF-␣, suggesting a potential role for Th1 responses in protection against invasive GAS infection following vaccination. abstract: Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-γ), and tumor necrosis alpha (TNF-α) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064752/ doi: 10.1128/mbio.00122-20 id: cord-296028-hqrd1e8p author: Rozell, Daniel J. title: Assessing and Managing the Risks of Potential Pandemic Pathogen Research date: 2015-07-21 words: 2584.0 sentences: 133.0 pages: flesch: 45.0 cache: ./cache/cord-296028-hqrd1e8p.txt txt: ./txt/cord-296028-hqrd1e8p.txt summary: Ultimately, the purpose of summarizing and critiquing some of the arguments within the GOF/PPP debate is to emphasize the many epistemic and ethical value judgments inherent to RBA and to provide evidence for prior claims that a consensus-building quantitative assessment is unlikely (1). As summarized here, many of the disagreements within the GOF/PPP debate involve epistemic and ethical value judgments that suggest that definitive quantitative risk-benefit analysis is not possible. Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion mBio addresses the pause in gain-offunction (GOF) experiments involving pathogens with pandemic potential (PPP) Conducting risk and benefit analysis on gain-of-function research involving pathogens with pandemic potential An epistemological perspective on the value of gain-of-function experiments involving pathogens with pandemic potential Vagueness and costs of the pause on gain-of-function (GOF) experiments on pathogens with pandemic potential, including influenza virus abstract: nan url: https://doi.org/10.1128/mbio.01075-15 doi: 10.1128/mbio.01075-15 id: cord-281389-sht0yx4a author: Tal, Michal Caspi title: Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition date: 2020-06-23 words: 7629.0 sentences: 382.0 pages: flesch: 46.0 cache: ./cache/cord-281389-sht0yx4a.txt txt: ./txt/cord-281389-sht0yx4a.txt summary: Examination of a publicly available gene expression data set (Gene Expression Omnibus [GEO] accession number GSE147507) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of A549 human lung cells also showed a significant upregulation of CD47 compared to mock-infected controls (Fig. 1D ). Multiple PBMC subsets showed significantly upregulated CD47 expression in response to Borrelia burgdorferi infection compared to naive cells (Fig. 1E) . Overall, the combined in vivo and in vitro results from multiple pathogen infections in both human and mouse cells indicated that the upregulation of CD47 was a conserved host response possibly related to host sensing mechanisms. Compared to healthy controls, monocytes and DCs from HCV patients demonstrated a sustained upregulation of CD47 at all treatment time points, including the 6-month posttreatment time point ( Fig. 3B (B) CD47 MFI on human total PBMCs from 4 separate donors stimulated with titrated concentrations of R848 from 0.1 g/ml to 10 g/ml, as indicated, for 48 h. abstract: It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 “don’t eat me” signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis. Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents. url: https://www.ncbi.nlm.nih.gov/pubmed/32576678/ doi: 10.1128/mbio.01293-20 id: cord-303262-grrd6jmt author: Tournier, Jean-Nicolas title: Pandemic Legion History More Complex than Previously Thought date: 2020-10-09 words: 699.0 sentences: 34.0 pages: flesch: 47.0 cache: ./cache/cord-303262-grrd6jmt.txt txt: ./txt/cord-303262-grrd6jmt.txt summary: Morens and colleagues describe in the "early pandemic history" section the story of pathogens emerging around 12,000 years ago at the time of Neolithic agricultural revolution. As such, diseases such as "measles, smallpox, tuberculosis (TB), [and] gastric cancer (caused by Helicobacter pylori)" are cited as consequences of "conditions of intense human-animal proximity and environmental alterations." This assertion of the dating of the origin of these aforementioned pathogens is partially misleading. Both viruses (i.e., those causing measles and smallpox) emerged probably much later, while Mycobacterium tuberculosis and Helicobacter pylori started their association with humans before the agricultural revolution. For smallpox, the exact date of divergence of variola virus (VARV) from a zoonotic strain is more disputed, as molecular data gave an estimation of emergence for the most recent common ancestor between the 16th and the 17th century, while skin lesions seen in the mummy of Ramses V, who died in 1157 BCE, suggested earlier interactions (6) . abstract: nan url: https://doi.org/10.1128/mbio.02377-20 doi: 10.1128/mbio.02377-20 id: cord-290297-efo9f7c5 author: Vaillancourt, Mylene title: The Unrecognized Threat of Secondary Bacterial Infections with COVID-19 date: 2020-08-07 words: 1354.0 sentences: 72.0 pages: flesch: 37.0 cache: ./cache/cord-290297-efo9f7c5.txt txt: ./txt/cord-290297-efo9f7c5.txt summary: In recent studies on COVID-19 patients, secondary bacterial infections were significantly associated with worse outcomes and death despite antimicrobial therapies. In the past, the intensive use of antibiotics during the severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic led to increases in the prevalence of multidrug-resistant bacteria. T he outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the greatest pandemic of our generation, with 16 million people infected and 650,000 deaths worldwide so far (1) . In a multicenter study that included 476 COVID-19 patients, secondary bacterial infections were significantly associated with outcome severity (2) . During the first SARS-CoV outbreak in 2003, up to 30% of patients were diagnosed with secondary bacterial infections and coinfection was positively associated with disease severity (5, 6) . Increase in methicillin-resistant Staphylococcus aureus acquisition rate and change in pathogen pattern associated with an outbreak of severe acute respiratory syndrome abstract: Coronavirus disease 2019 (COVID-19) is the greatest pandemic of our generation, with 16 million people affected and 650,000 deaths worldwide so far. One of the risk factors associated with COVID-19 is secondary bacterial pneumonia. In recent studies on COVID-19 patients, secondary bacterial infections were significantly associated with worse outcomes and death despite antimicrobial therapies. In the past, the intensive use of antibiotics during the severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic led to increases in the prevalence of multidrug-resistant bacteria. The rising number of antibiotic-resistant bacteria and our decreasing capacity to eradicate them not only render us more vulnerable to bacterial infections but also weaken us during viral pandemics. The COVID-19 pandemic reminds us of the great health challenges we are facing, especially regarding antibiotic-resistant bacteria. url: https://www.ncbi.nlm.nih.gov/pubmed/32769090/ doi: 10.1128/mbio.01806-20 id: cord-252671-uf96jgig author: Wang, Yi title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism date: 2016-02-09 words: 7390.0 sentences: 389.0 pages: flesch: 52.0 cache: ./cache/cord-252671-uf96jgig.txt txt: ./txt/cord-252671-uf96jgig.txt summary: title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production. The result of a dual-luciferase assay using the Renilla luciferase gene as a transfection control demonstrated that the SARS-CoV M gene rather than the S and E genes markedly increased IFN-␤ promoter activity (Fig. 1D) , whereas the valineto-alanine alteration at residue 68 of M protein completely abolished this induction, indicating that the specificity of M gene products played a role in this process. Taken together, our data indicate for the first time that SARS-CoV M protein may function as a novel cytosolic PAMP to activate IFN-␤ induction through an intracellular TLR-related signaling pathway in a TRAF3-independent manner. abstract: Most of the intracellular pattern recognition receptors (PRRs) reside in either the endolysosome or the cytoplasm to sense pathogen-derived RNAs, DNAs, or synthetic analogs of double-stranded RNA (dsRNA), such as poly(I:C). However, it remains elusive whether or not a pathogen-derived protein can function as a cytosolic pathogen-associated molecular pattern (PAMP). In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production. Both NF-κB and TBK1-IRF3 signaling cascades are activated by M gene products. M protein rather than M mRNA is responsible for M-mediated IFN-β induction that is preferentially associated with the activation of the Toll-like receptor (TLR) adaptor proteins MyD88, TIRAP, and TICAM2 but not the RIG-I signaling cascade. Blocking the secretion of M protein by brefeldin A (BFA) failed to reverse the M-mediated IFN-β induction. The antagonist of both TLR2 and TLR4 did not impede M-mediated IFN-β induction, indicating that the driving force for the activation of IFN-β production was generated from inside the cells. Inhibition of TRAF3 expression by specific small interfering RNA (siRNA) did not prevent M-mediated IFN-β induction. SARS-CoV pseudovirus could induce IFN-β production in an M rather than M(V68A) dependent manner, since the valine-to-alanine alteration at residue 68 in M protein markedly inhibited IFN-β production. Overall, our study indicates for the first time that a pathogen-derived protein is able to function as a cytosolic PAMP to stimulate type I interferon production by activating a noncanonical TLR signaling cascade in a TRAF3-independent manner. url: https://www.ncbi.nlm.nih.gov/pubmed/26861016/ doi: 10.1128/mbio.01872-15 id: cord-327660-p1b07b4t author: Wolf, Yuri I. title: Origins and Evolution of the Global RNA Virome date: 2018-11-27 words: 13927.0 sentences: 658.0 pages: flesch: 45.0 cache: ./cache/cord-327660-p1b07b4t.txt txt: ./txt/cord-327660-p1b07b4t.txt summary: The current RdRp tree topology combined with gene gain-loss reconstruction suggests the following evolutionary scenario for branch 1 ( Fig. 2A) : a levivirus-like ancestor that, like the extant members of the Leviviridae, possessed a capsid protein unrelated to SJR-CP (19, 52) gave rise to naked eukaryotic RNA replicons known as "mitoviruses" and "narnaviruses." These replicons consist of a single RdRp gene (Fig. 2B ) and replicate in mitochondria and in the cytosol of the host cells of fungal and invertebrate hosts, respectively (the latter hosts were identified in metaviromic holobiont analyses) (14, 53) . This genome architecture could hint at an ancestral flavivirus genome that was assembled from genes borrowed from preexisting viruses, one of which possessed a divergent "tombus-like virus" RdRp. Although the origins of branch 3 are murky, major trends in its subsequent evolution clearly included lineage-specific gene capture, starting with helicases and CapEs in the ancestors of the major lineages and followed by diverse genes in smaller groups (Fig. 4B) . abstract: Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy. url: https://www.ncbi.nlm.nih.gov/pubmed/30482837/ doi: 10.1128/mbio.02329-18 id: cord-297082-2rhoffx2 author: Yu, Changqing title: MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date: 2020-09-15 words: 6423.0 sentences: 410.0 pages: flesch: 61.0 cache: ./cache/cord-297082-2rhoffx2.txt txt: ./txt/cord-297082-2rhoffx2.txt summary: Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. As a control, serine incorporator 5 (SERINC5) protein In addition, FLAG-tagged furin was expressed with HA-tagged human MARCH8 and GPΔMLD in 293T cells. In addition, when the furin-VN/GP-VC pair was expressed with MARCH8, their colocalization was also detected (Fig. 2C ), confirming that these three molecules form a complex in live cells. MARCH8 proteins from different species strongly increased GP 1 and GP 1 ΔMLD expression in cells but completely blocked their secretions (Fig. 7C, lanes 1 to 8) . abstract: Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We now report that MARCH8 also blocks the Ebola virus (EBOV) glycoprotein (GP) incorporation via surface downregulation. To understand how these viral fusion proteins are downregulated, we investigated the effects of MARCH8 on EBOV GP maturation and externalization via the conventional secretion pathway. MARCH8 interacted with EBOV GP and furin when detected by immunoprecipitation and retained the GP/furin complex in the Golgi when their location was tracked by a bimolecular fluorescence complementation (BiFC) assay. MARCH8 did not reduce the GP expression or affect the GP modification by high-mannose N-glycans in the endoplasmic reticulum (ER), but it inhibited the formation of complex N-glycans on the GP in the Golgi. Additionally, the GP O-glycosylation and furin-mediated proteolytic cleavage were also inhibited. Moreover, we identified a novel furin cleavage site on EBOV GP and found that only those fully glycosylated GPs were processed by furin and incorporated into virions. Furthermore, the GP shedding and secretion were all blocked by MARCH8. MARCH8 also blocked the furin-mediated cleavage of HIV-1 Env (gp160) and the highly pathogenic avian influenza virus H5N1 hemagglutinin (HA). We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. url: https://www.ncbi.nlm.nih.gov/pubmed/32934085/ doi: 10.1128/mbio.01882-20 id: cord-003143-n6b0r92e author: Zhao, Min title: Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses date: 2018-08-07 words: 7938.0 sentences: 432.0 pages: flesch: 55.0 cache: ./cache/cord-003143-n6b0r92e.txt txt: ./txt/cord-003143-n6b0r92e.txt summary: However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed crossbut biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Thus, to investigate the contribution of different cellular antigens of influenza viruses to biased cross-T-cell reactivities, we compared T-cell responses to H7N9 and pH1N1 among the members of the healthy population using overlapping peptides covering the M1 and NP proteins. Further analysis indicated that these peptides contained previously identified HLA class I-or class II-restricted epitopes (see Fig. S2D and H) and that the immunogenicity can be influenced by the substitutions in different AIVs. Phenotypes of the cross-reactive T-cell. abstract: Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083907/ doi: 10.1128/mbio.01408-18 id: cord-326160-mf0vh6iu author: de Wit, Emmie title: Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques date: 2014-08-12 words: 6428.0 sentences: 318.0 pages: flesch: 42.0 cache: ./cache/cord-326160-mf0vh6iu.txt txt: ./txt/cord-326160-mf0vh6iu.txt summary: Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. To elucidate global host responses specifically associated with sites of virus-induced airway injury in influenza virus A/Anhui/1/2013-infected macaques, we used microarrays to assess transcriptional profiles induced in lung lesions compared to the adjacent lung tissue. We identified ten compounds in IPA (Table 1) , four of which were perturbagens listed in CMap. We identified two compounds that met our criteria in IPA and CMap, rosiglitazone and simvastatin, predicted to have inhibitory effects on pathological host responses associated with lesions in influenza virus A/Anhui/1/2013-infected animals ( Table 1) . abstract: In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584). url: https://www.ncbi.nlm.nih.gov/pubmed/25118237/ doi: 10.1128/mbio.01331-14 ==== 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