{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:36:47Z","timestamp":1791992207492,"version":"4.4.0"},"reference-count":66,"publisher":"Rockefeller University Press","issue":"1","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Women\u2019s Health Research at Yale Pilot Project Program"},{"name":"Mathers Family Foundation"},{"DOI":"10.13039\/100018128","name":"Ludwig Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI157488-01"],"award-info":[{"award-number":["1R01AI157488-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01AI127429-04"],"award-info":[{"award-number":["5R01AI127429-04"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Emergent Ventures"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007019"],"award-info":[{"award-number":["T32AI007019"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["2T32AI007517-16"],"award-info":[{"award-number":["2T32AI007517-16"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08AI163493"],"award-info":[{"award-number":["K08AI163493"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research","award":["019.181EN.004"],"award-info":[{"award-number":["019.181EN.004"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08AI128043"],"award-info":[{"award-number":["K08AI128043"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1,3]]},"abstract":"<jats:p>As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)\u2013dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients.<\/jats:p>","DOI":"10.1084\/jem.20211818","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T02:21:42Z","timestamp":1635474102000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9251-8592","authenticated-orcid":true,"given":"Tianyang","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1308-8246","authenticated-orcid":true,"given":"Benjamin","family":"Israelow","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"},{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4590-2756","authenticated-orcid":true,"given":"Carolina","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0027-6480","authenticated-orcid":true,"given":"Chantal B.F.","family":"Vogels","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3852-9140","authenticated-orcid":true,"given":"Maria Luisa","family":"Gomez-Calvo","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-7358","authenticated-orcid":true,"given":"Olga","family":"Fedorova","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 4"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-9988","authenticated-orcid":true,"given":"Mallery I.","family":"Breban","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3520-2422","authenticated-orcid":true,"given":"Bridget L.","family":"Menasche","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-0868","authenticated-orcid":true,"given":"Huiping","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-4946","authenticated-orcid":true,"given":"Melissa","family":"Linehan","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Yale SARS-CoV-2 Genome Surveillance Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Alpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Brito","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Earnest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Fauver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaney C.","family":"Kalinich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketty","family":"Munyenyembe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel M.","family":"Ott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Petrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Rothman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2495-9403","authenticated-orcid":true,"given":"Craig B.","family":"Wilen","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"},{"name":"Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5543-8366","authenticated-orcid":true,"given":"Marie L.","family":"Landry","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 2"},{"name":"Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2031-1933","authenticated-orcid":true,"given":"Nathan D.","family":"Grubaugh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 3"},{"name":"Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-8872","authenticated-orcid":true,"given":"Anna M.","family":"Pyle","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 4"},{"name":"Department of Chemistry, Yale University, New Haven, CT 7"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7824-9856","authenticated-orcid":true,"given":"Akiko","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, CT 1"},{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 3"},{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 4"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 8"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"2023072812500141900_bib1","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1016\/j.cell.2021.03.061","article-title":"Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States","volume":"184","author":"Alpert","year":"2021","journal-title":"Cell."},{"key":"2023072812500141900_bib2","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1056\/NEJMc2031670","article-title":"Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer","volume":"383","author":"Aydillo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib3","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"Bastard","year":"2020","journal-title":"Science."},{"key":"2023072812500141900_bib4","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the Treatment of Covid-19 - Final Report","volume":"383","author":"Beigel","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib5","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.88a.ccc073","article-title":"Baricitinib and dexamethasone for hospitalized patients with COVID-19","author":"Calabrese","year":"2021","journal-title":"Cleve. Clin. J.                        Med."},{"key":"2023072812500141900_bib6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41577-021-00522-1","article-title":"The first 12 months of COVID-19: a timeline of immunological insights","volume":"21","author":"Carvalho","year":"2021","journal-title":"Nat. Rev.                        Immunol."},{"key":"2023072812500141900_bib7","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/s41586-020-2600-6","article-title":"Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis","volume":"588","author":"Carvelli","year":"2020","journal-title":"Nature."},{"key":"2023072812500141900_bib8","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1056\/NEJMc2031364","article-title":"Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host","volume":"383","author":"Choi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib9","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41586-021-03412-7","article-title":"Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies","volume":"593","author":"Collier","year":"2021","journal-title":"Nature."},{"key":"2023072812500141900_bib71","doi-asserted-by":"publisher","DOI":"10.7326\/M21-1757","article-title":"Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2: A Prospective Cohort Study","author":"Deepak","year":"2021","journal-title":"Ann Intern Med"},{"key":"2023072812500141900_bib11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41586-019-1593-5","article-title":"Harnessing innate immunity in cancer therapy","volume":"574","author":"Demaria","year":"2019","journal-title":"Nature."},{"key":"2023072812500141900_bib12","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1136\/jnnp.73.5.465","article-title":"Neutralising antibodies to interferon beta during the treatment of multiple sclerosis","volume":"73","author":"Giovannoni","year":"2002","journal-title":"J.                        Neurol. Neurosurg. Psychiatry."},{"key":"2023072812500141900_bib13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003298","article-title":"Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity","volume":"9","author":"Goulet","year":"2013","journal-title":"PLoS Pathog."},{"key":"2023072812500141900_bib14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13059-018-1618-7","article-title":"An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar","volume":"20","author":"Grubaugh","year":"2019","journal-title":"Genome Biol."},{"key":"2023072812500141900_bib15","doi-asserted-by":"crossref","unstructured":"Guo,                            K.,                                B.S.Barrett,                                K.L.Mickens,                                K.J.Hasenkrug, and                                M.L.Santiago.                        2021. Interferon Resistance of Emerging SARS-CoV-2 Variants.bioRxiv.10.1101\/2021.03.20.436257 (Preprint posted March 21, 2021)","DOI":"10.1101\/2021.03.20.436257"},{"key":"2023072812500141900_bib16","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.immuni.2021.01.017","article-title":"Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity","volume":"54","author":"Hoagland","year":"2021","journal-title":"Immunity."},{"key":"2023072812500141900_bib17","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1016\/j.cell.2021.03.036","article-title":"SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies","volume":"184","author":"Hoffmann","year":"2021","journal-title":"Cell."},{"key":"2023072812500141900_bib18","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1056\/NEJMoa2021436","article-title":"Dexamethasone in Hospitalized Patients with Covid-19","volume":"384","author":"Horby","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib19","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"2023072812500141900_bib20","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1182\/blood.2020008423","article-title":"Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19","volume":"136","author":"Hueso","year":"2020","journal-title":"Blood."},{"key":"2023072812500141900_bib21","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi9002","article-title":"A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection","volume":"6","author":"Humphries","year":"2021","journal-title":"Sci.                        Immunol."},{"key":"2023072812500141900_bib70","doi-asserted-by":"publisher","first-page":"eabl4509","DOI":"10.1126\/sciimmunol.abl4509","article-title":"Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2","author":"Israelow","year":"2021","journal-title":"Sci. Immunol"},{"key":"2023072812500141900_bib22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201241","article-title":"Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling","volume":"217","author":"Israelow","year":"2020","journal-title":"J.                        Exp. Med."},{"key":"2023072812500141900_bib24","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/ni.3123","article-title":"Control of adaptive immunity by the innate immune system","volume":"16","author":"Iwasaki","year":"2015","journal-title":"Nat. Immunol."},{"key":"2023072812500141900_bib25","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.1084\/jem.20190801","article-title":"Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses","volume":"216","author":"Jiang","year":"2019","journal-title":"J. Exp.                        Med."},{"key":"2023072812500141900_bib26","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1056\/NEJMoa2031994","article-title":"Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19","volume":"384","author":"Kalil","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000869","article-title":"Real-time public health communication of local SARS-CoV-2 genomic epidemiology","volume":"18","author":"Kalinich","year":"2020","journal-title":"PLoS Biol."},{"key":"2023072812500141900_bib28","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41586-021-03291-y","article-title":"SARS-CoV-2 evolution during treatment of chronic infection","volume":"592","author":"Kemp","year":"2021","journal-title":"Nature."},{"key":"2023072812500141900_bib29","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1001\/jama.2020.10044","article-title":"Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial","volume":"324","author":"Li","year":"2020","journal-title":"JAMA."},{"key":"2023072812500141900_bib30","unstructured":"Li,                            B.,                                A.Deng,                                K.Li,                                Y.Hu,                                Z.Li, and                                J.Lu.                        2021a. Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.medRxiv.10.1101\/2021.07.07.21260122 (Preprint posted July 23, 2021)"},{"key":"2023072812500141900_bib31","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi9007","article-title":"Pharmacological activation of STING blocks SARS-CoV-2 infection","volume":"6","author":"Li","year":"2021","journal-title":"Sci. Immunol."},{"key":"2023072812500141900_bib32","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1701854","article-title":"A minimal RNA ligand for potent RIG-I activation in living mice","volume":"4","author":"Linehan","year":"2018","journal-title":"Sci. Adv."},{"key":"2023072812500141900_bib33","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.chom.2021.05.004","article-title":"Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19","volume":"29","author":"Lowery","year":"2021","journal-title":"Cell Host Microbe."},{"key":"2023072812500141900_bib68","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04085-y.","article-title":"Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity","author":"Lucas","year":"2021","journal-title":"Nature"},{"key":"2023072812500141900_bib34","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature."},{"key":"2023072812500141900_bib36","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.cell.2011.09.023","article-title":"Structural insights into RNA recognition by RIG-I","volume":"147","author":"Luo","year":"2011","journal-title":"Cell."},{"key":"2023072812500141900_bib37","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1111\/j.1365-2893.2012.01598.x","article-title":"Anti-interferon-\u03b1 neutralizing antibody is associated with nonresponse to pegylated interferon-\u03b1                        plus ribavirin in chronic hepatitis C","volume":"19","author":"Matsuda","year":"2012","journal-title":"J. Viral Hepat."},{"key":"2023072812500141900_bib38","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1128\/JVI.02012-06","article-title":"Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus","volume":"81","author":"McCray","year":"2007","journal-title":"J. Virol."},{"key":"2023072812500141900_bib39","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/d41586-020-03070-1","article-title":"Interferon deficiency can lead to severe COVID","volume":"587","author":"Meffre","year":"2020","journal-title":"Nature."},{"key":"2023072812500141900_bib40","doi-asserted-by":"publisher","first-page":"129","DOI":"10.12688\/wellcomeopenres.15408.2","article-title":"The direct-medical costs associated with interferon-based treatment for Hepatitis C in Vietnam","volume":"4","author":"Nguyen","year":"2020","journal-title":"Wellcome Open Res."},{"key":"2023072812500141900_bib41","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.chom.2020.05.008","article-title":"Type I and Type III Interferons -                        Induction, Signaling, Evasion, and Application to Combat COVID-19","volume":"27","author":"Park","year":"2020","journal-title":"Cell Host Microbe."},{"key":"2023072812500141900_bib42","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/s41591-021-01318-5","article-title":"Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies","volume":"27","author":"Planas","year":"2021","journal-title":"Nat. Med."},{"key":"2023072812500141900_bib43","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","article-title":"Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization","volume":"596","author":"Planas","year":"2021","journal-title":"Nature."},{"key":"2023072812500141900_bib44","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/s41586-018-0705-y","article-title":"Design of amidobenzimidazole STING receptor agonists with systemic activity","volume":"564","author":"Ramanjulu","year":"2018","journal-title":"Nature."},{"key":"2023072812500141900_bib45","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/s41577-020-0288-3","article-title":"RIG-I-like receptors: their regulation and roles in RNA sensing","volume":"20","author":"Rehwinkel","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"2023072812500141900_bib46","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1056\/NEJMoa2028700","article-title":"Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia","volume":"384","author":"Rosas","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib47","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: a complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"2023072812500141900_bib48","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1056\/NEJMoa2031304","article-title":"A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia","volume":"384","author":"Simonovich","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"2023072812500141900_bib49","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/s41577-021-00542-x","article-title":"Neutralizing monoclonal antibodies for treatment of COVID-19","volume":"21","author":"Taylor","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"2023072812500141900_bib50","doi-asserted-by":"crossref","unstructured":"Thorne,                                L.G.,                                M.Bouhaddou,                                A.K.Reuschl,                                L.Zuliani-Alvarez,                                B.Polacco,                                A.Pelin,                                J.Batra,                                M.V.X.Whelan,                                M.Ummadi,                                A.Rojc, .                        2021. Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant.bioRxiv.10.1101\/2021.06.06.446826 (Preprint posted June 7, 2021)","DOI":"10.1101\/2021.06.06.446826"},{"key":"2023072812500141900_bib51","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1016\/j.celrep.2018.11.030","article-title":"ISRE-Reporter Mouse Reveals High Basal and Induced Type I IFN Responses in Inflammatory Monocytes","volume":"25","author":"Uccellini","year":"2018","journal-title":"Cell Rep."},{"key":"2023072812500141900_bib52","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication:                        implications for SARS-CoV-2","volume":"19","author":"V\u2019kovski","year":"2021","journal-title":"Nat. Rev.                        Microbiol."},{"key":"2023072812500141900_bib53","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41573-019-0043-2","article-title":"Pharmacological modulation of nucleic acid sensors - therapeutic potential and persisting obstacles","volume":"18","author":"Vanpouille-Box","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023072812500141900_bib54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001236","article-title":"Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2","volume":"19","author":"Vogels","year":"2021","journal-title":"PLoS Biol."},{"key":"2023072812500141900_bib55","author":"Vogels","year":"2021"},{"key":"2023072812500141900_bib56","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.dci.2014.03.013","article-title":"Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective","volume":"48","author":"Wang","year":"2015","journal-title":"Dev. Comp.                        Immunol."},{"key":"2023072812500141900_bib67","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41586-021-03631-y","article-title":"Diverse functional autoantibodies in patients with COVID-19","volume":"595","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"2023072812500141900_bib58","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.chom.2020.07.005","article-title":"Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients","volume":"28","author":"Wang","year":"2020","journal-title":"Cell Host Microbe."},{"key":"2023072812500141900_bib59","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1016\/j.cell.2021.03.052","article-title":"Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States","volume":"184","author":"Washington","year":"2021","journal-title":"Cell."},{"key":"2023072812500141900_bib60","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1038\/s41590-020-0778-2","article-title":"SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function","volume":"21","author":"Winkler","year":"2020","journal-title":"Nat. Immunol."},{"key":"2023072812500141900_bib61","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/s41590-021-00942-0","article-title":"RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells","volume":"22","author":"Yamada","year":"2021","journal-title":"Nat.                        Immunol."},{"key":"2023072812500141900_bib62","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108628","article-title":"MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells","volume":"34","author":"Yin","year":"2021","journal-title":"Cell Rep."},{"key":"2023072812500141900_bib63","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4570","article-title":"Inborn errors of type I IFN immunity in patients with life-threatening COVID-19","volume":"370","author":"Zhang","year":"2020","journal-title":"Science."},{"key":"2023072812500141900_bib64","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/s41586-020-2943-z","article-title":"COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice","volume":"589","author":"Zheng","year":"2021","journal-title":"Nature."},{"key":"2023072812500141900_bib65","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1016\/j.cell.2021.02.037","article-title":"Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera","volume":"184","author":"Zhou","year":"2021","journal-title":"Cell."},{"key":"2023072812500141900_bib66","doi-asserted-by":"crossref","unstructured":"Zhou,                            H.,                                B.M.Dcosta,                                M.I.Samanovic,                                M.J.Mulligan,                                N.R.Landau, and                                T.Tada.                        2021b. B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies.bioRxiv.10.1101\/2021.03.24.436620 (Preprint posted March 24, 2021)","DOI":"10.1101\/2021.03.24.436620"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20211818\/1833067\/jem_20211818.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20211818\/1833067\/jem_20211818.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T08:52:18Z","timestamp":1690534338000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/219\/1\/e20211818\/212765\/A-stem-loop-RNA-RIG-I-agonist-protects-against"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,3]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20211818","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.16.448754","asserted-by":"object"}]},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,10]]},"article-number":"e20211818"}}