{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:48:34Z","timestamp":1791236914312,"version":"4.1.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection.<\/jats:p>","DOI":"10.3389\/fcimb.2021.689707","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T06:53:18Z","timestamp":1632207198000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection"],"prefix":"10.3389","volume":"11","author":[{"given":"Matthew","family":"Charman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"McFarlane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna K.","family":"Wojtus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sloan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Dewar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Leeming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al-Saadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles W.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Digard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Hutchinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Boutell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/mi.2017.45","article-title":"An Innate Defense Peptide BPIFA1\/SPLUNC1 Restricts Influenza A Virus Infection","volume":"11","author":"Akram","year":"2018","journal-title":"Mucosal Immunol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02611","article-title":"Host Intrinsic and Innate Intracellular Immunity During Herpes Simplex Virus Type 1 (HSV-1) Infection","volume":"10","author":"Alandijany","year":"2019","journal-title":"Front. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia Enables Predictive Modelling of Anticancer Drug Sensitivity","volume":"483","author":"Barretina","year":"2012","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1000007","DOI":"10.1371\/journal.ppat.1000007","article-title":"The Interferon Response Inhibits HIV Particle Production by Induction of TRIM22","volume":"4","author":"Barr","year":"2008","journal-title":"PloS Pathog."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cells8080922","article-title":"Interplay Between Intrinsic and Innate Immunity During HIV Infection","volume":"8","author":"Bergantz","year":"2019","journal-title":"Cells"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/ni1125","article-title":"Intrinsic Immunity: A Front-Line Defense Against Viral Attack","volume":"5","author":"Bieniasz","year":"2004","journal-title":"Nat. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.celrep.2019.05.105","article-title":"Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect From Influenza Virus Infection","volume":"28","author":"Bradley","year":"2019","journal-title":"Cell Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.cell.2009.12.017","article-title":"The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus","volume":"139","author":"Brass","year":"2009","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1089\/bio.2015.0032","article-title":"A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project","volume":"13","author":"Carithers","year":"2015","journal-title":"Biopreserv. Biobank"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4807","DOI":"10.1128\/JVI.03055-15","article-title":"Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response","volume":"90","author":"Conn","year":"2016","journal-title":"J. Virol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1128\/JVI.02548-12","article-title":"TRIM22 Inhibits Influenza A Virus Infection by Targeting the Viral Nucleoprotein for Degradation","volume":"87","author":"Di Pietro","year":"2013","journal-title":"J. Virol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/imr.12101","article-title":"Interferon Induction and Function at the Mucosal Surface","volume":"255","author":"Durbin","year":"2013","journal-title":"Immunol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/nrmicro3367","article-title":"At the Centre: Influenza A Virus Ribonucleoproteins","volume":"13","author":"Eisfeld","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1099\/vir.0.006288-0","article-title":"TRIM22 E3 Ubiquitin Ligase Activity is Required to Mediate Antiviral Activity Against Encephalomyocarditis Virus","volume":"90","author":"Eldin","year":"2009","journal-title":"J. Gen. Virol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"7995","DOI":"10.1128\/JVI.00734-06","article-title":"PML Contributes to a Cellular Mechanism of Repression of Herpes Simplex Virus Type 1 Infection That is Inactivated by ICP0","volume":"80","author":"Everett","year":"2006","journal-title":"J. Virol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0355-5","article-title":"Cell Composition Analysis of Bulk Genomics Using Single-Cell Data","volume":"16","author":"Frishberg","year":"2019","journal-title":"Nat. Methods"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e1004960","DOI":"10.1371\/journal.ppat.1004960","article-title":"TRIM32 Senses and Restricts Influenza A Virus by Ubiquitination of PB1 Polymerase","volume":"11","author":"Fu","year":"2015","journal-title":"PloS Pathog."},{"key":"B18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/hep.23011","article-title":"Tripartite Motif-Containing 22 Inhibits the Activity of Hepatitis B Virus Core Promoter, Which is Dependent on Nuclear-Located RING Domain","volume":"50","author":"Gao","year":"2009","journal-title":"Hepatology"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1186-3","article-title":"Next-Generation Characterization of the Cancer Cell Line Encyclopedia","volume":"569","author":"Ghandi","year":"2019","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.immuni.2012.01.011","article-title":"Constitutive Type I Interferon Modulates Homeostatic Balance Through Tonic Signaling","volume":"36","author":"Gough","year":"2012","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","first-page":"23","DOI":"10.2217\/fmb.09.108","article-title":"Innate Immune Evasion Strategies of Influenza Viruses","volume":"5","author":"Hale","year":"2010","journal-title":"Future Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"153415","DOI":"10.1155\/2012\/153415","article-title":"TRIM22: A Diverse and Dynamic Antiviral Protein","volume":"2012","author":"Hattlmann","year":"2012","journal-title":"Mol. Biol. Int."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00743","article-title":"Influenza Virus: A Master Tactician in Innate Immune Evasion and Novel Therapeutic Interventions","volume":"9","author":"Hsu","year":"2018","journal-title":"Front. Immunol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2018.05.013","article-title":"Influenza Virus","volume":"26","author":"Hutchinson","year":"2018","journal-title":"Trends Microbiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"11869","DOI":"10.1128\/JVI.01634-08","article-title":"Mutational Analysis of Cis-Acting RNA Signals in Segment 7 of Influenza A Virus","volume":"82","author":"Hutchinson","year":"2008","journal-title":"J. Virol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate Immunity to Influenza Virus Infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.virusres.2015.02.003","article-title":"Influenza Virus Activation of the Interferon System","volume":"209","author":"Killip","year":"2015","journal-title":"Virus Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1099\/jgv.0.000687","article-title":"Single-Cell Studies of IFN-Beta Promoter Activation by Wild-Type and NS1-Defective Influenza A Viruses","volume":"98","author":"Killip","year":"2017","journal-title":"J. Gen. Virol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.mib.2020.07.005","article-title":"The Antiviral Activities of TRIM Proteins","volume":"59","author":"Koepke","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v8100290","article-title":"The Role of Nuclear Antiviral Factors Against Invading DNA Viruses: The Immediate Fate of Incoming Viral Genomes","volume":"8","author":"Komatsu","year":"2016","journal-title":"Viruses"},{"key":"B31","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/sj.icb.7100026","article-title":"A Question of Self-Preservation: Immunopathology in Influenza Virus Infection","volume":"85","author":"La Gruta","year":"2007","journal-title":"Immunol. Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/labinvest.2014.162","article-title":"Gammaherpesvirus Infection Modulates the Temporal and Spatial Expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the Respiratory Tract","volume":"95","author":"Leeming","year":"2015","journal-title":"Lab. Invest."},{"key":"B33","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.molmed.2018.06.004","article-title":"Host-Intrinsic Interferon Status in Infection and Immunity","volume":"24","author":"Liu","year":"2018","journal-title":"Trends Mol. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/cmi.2015.74","article-title":"The Cytokine Storm of Severe Influenza and Development of Immunomodulatory Therapy","volume":"13","author":"Liu","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e0157887","DOI":"10.1371\/journal.pone.0157887","article-title":"Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection","volume":"11","author":"Marriott","year":"2016","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/jmv.20942","article-title":"Microarray Analyses of Differentially Expressed Human Genes and Biological Processes in ECV304 Cells Infected With Rubella Virus","volume":"79","author":"Mo","year":"2007","journal-title":"J. Med. Virol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4050","DOI":"10.1038\/sj.onc.1207524","article-title":"Staf50 is a Novel P53 Target Gene Conferring Reduced Clonogenic Growth of Leukemic U-937 Cells","volume":"23","author":"Obad","year":"2004","journal-title":"Oncogene"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/mSphere.00110-18","article-title":"Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses Between 1918 and 2009","volume":"3","author":"Pagani","year":"2018","journal-title":"mSphere"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/JVI.00905-18","article-title":"TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Influenza A Virus Infection","volume":"92","author":"Patil","year":"2018","journal-title":"J. Virol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/82_2014_405","article-title":"Innate Immune Sensing and Response to Influenza","volume":"386","author":"Pulendran","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"9027","DOI":"10.1158\/0008-5472.CAN-04-3703","article-title":"Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins","volume":"64","author":"Ramirez","year":"2004","journal-title":"Cancer Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e1009281","DOI":"10.1371\/journal.ppat.1009281","article-title":"Tripartite Motif 22 (TRIM22) Protein Restricts Herpes Simplex Virus 1 by Epigenetic Silencing of Viral Immediate-Early Genes","volume":"17","author":"Reddi","year":"2021","journal-title":"PloS Pathog."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00500-19","article-title":"Single-Cell Virus Sequencing of Influenza Infections That Trigger Innate Immunity","volume":"93","author":"Russell","year":"2019","journal-title":"J. Virol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/nature12862","article-title":"Pan-Viral Specificity of IFN-Induced Genes Reveals New Roles for cGAS in Innate Immunity","volume":"505","author":"Schoggins","year":"2014","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature09907","article-title":"A Diverse Range of Gene Products are Effectors of the Type I Interferon Antiviral Response","volume":"472","author":"Schoggins","year":"2011","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e2004086","DOI":"10.1371\/journal.pbio.2004086","article-title":"Fundamental Properties of the Mammalian Innate Immune System Revealed by Multispecies Comparison of Type I Interferon Responses","volume":"15","author":"Shaw","year":"2017","journal-title":"PloS Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v9080223","article-title":"Influenza Virus Infection, Interferon Response, Viral Counter-Response, and Apoptosis","volume":"9","author":"Shim","year":"2017","journal-title":"Viruses"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e58233","DOI":"10.1371\/journal.pone.0058233","article-title":"hTERT Extends the Life of Human Fibroblasts Without Compromising Type I Interferon Signaling","volume":"8","author":"Smith","year":"2013","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.cell.2020.10.047","article-title":"Commensal Microbiota Modulation of Natural Resistance to Virus Infection","volume":"183","author":"Stefan","year":"2020","journal-title":"Cell"},{"key":"B50","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.cels.2018.05.008","article-title":"Dissection of Influenza Infection In Vivo by Single-Cell RNA Sequencing","volume":"6","author":"Steuerman","year":"2018","journal-title":"Cell Syst."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e112014","DOI":"10.1371\/journal.pone.0112014","article-title":"Inhibitors of the Interferon Response Enhance Virus Replication In Vitro","volume":"9","author":"Stewart","year":"2014","journal-title":"PloS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e1003703","DOI":"10.1371\/journal.ppat.1003703","article-title":"Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity","volume":"9","author":"Tapia","year":"2013","journal-title":"PloS Pathog."},{"key":"B53","doi-asserted-by":"publisher","first-page":"5038","DOI":"10.1073\/pnas.84.14.5038","article-title":"Interferon Messenger RNA is Produced Constitutively in the Organs of Normal Individuals","volume":"84","author":"Tovey","year":"1987","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B54","doi-asserted-by":"publisher","first-page":"9263","DOI":"10.1128\/JVI.01205-16","article-title":"Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity","volume":"90","author":"Turnbull","year":"2016","journal-title":"J. Virol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12977-015-0230-0","article-title":"HIV-1 Transcriptional Silencing Caused by TRIM22 Inhibition of Sp1 Binding to the Viral Promoter","volume":"12","author":"Turrini","year":"2015","journal-title":"Retrovirology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-Based Map of the Human Proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/nbt1210-1248","article-title":"Towards a Knowledge-Based Human Protein Atlas","volume":"28","author":"Uhlen","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-092917-043323","article-title":"TRIM Proteins and Their Roles in Antiviral Host Defenses","volume":"5","author":"Van Gent","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/vaccines5030023","article-title":"The TRIMendous Role of TRIMs in Virus-Host Interactions","volume":"5","author":"Van Tol","year":"2017","journal-title":"Vaccines (Basel)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e1006650","DOI":"10.1371\/journal.ppat.1006650","article-title":"Reduced Accumulation of Defective Viral Genomes Contributes to Severe Outcome in Influenza Virus Infected Patients","volume":"13","author":"Vasilijevic","year":"2017","journal-title":"PloS Pathog."},{"key":"B61","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jviromet.2010.04.017","article-title":"Real-Time RT-qPCR Assay for the Analysis of Human Influenza A Virus Transcription and Replication Dynamics","volume":"168","author":"Vester","year":"2010","journal-title":"J. Virol. Methods"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v9120376","article-title":"Host Cell Restriction Factors That Limit Influenza A Infection","volume":"9","author":"Villalon-Letelier","year":"2017","journal-title":"Viruses"},{"key":"B63","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.cell.2017.11.018","article-title":"Intrinsic Immunity Shapes Viral Resistance of Stem Cells","volume":"172","author":"Wu","year":"2018","journal-title":"Cell"},{"key":"B64","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A New Coronavirus Associated With Human Respiratory Disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/cmi.2014.131","article-title":"Interferon Alpha (IFNalpha)-Induced TRIM22 Interrupts HCV Replication by Ubiquitinating NS5A","volume":"13","author":"Yang","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus From Patients With Pneumonia in Chin","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.689707\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T06:53:21Z","timestamp":1632207201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.689707\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,21]]},"references-count":66,"alternative-id":["10.3389\/fcimb.2021.689707"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.689707","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,21]]},"article-number":"689707"}}