{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:40:27Z","timestamp":1790746827237,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R151-2013-14668"],"award-info":[{"award-number":["R151-2013-14668"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008267","name":"Kong Christian den Tiendes Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008267","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Christian Larsen og Dommer Ellen Larsens Legat"},{"DOI":"10.13039\/501100004836","name":"Danish Council for Independent Research","doi-asserted-by":"publisher","award":["4004-00047B"],"award-info":[{"award-number":["4004-00047B"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002739","name":"Aarhus University Research Fund","doi-asserted-by":"publisher","award":["AUFF-E-2015-FLS-66"],"award-info":[{"award-number":["AUFF-E-2015-FLS-66"]}],"id":[{"id":"10.13039\/501100002739","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Simon Fougner Hartmanns Fond"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,25]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Influenza virus infection causes worldwide seasonal epidemics. Although influenza is usually a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in anti-viral responses during influenza. So far, however, IFN regulatory factor (IRF)7 deficiency is the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 swine flu pandemic. By whole exome sequencing we identified two variants, p.R71H and p.P885S, located in the caspase activation and recruitment domain (CARD) and RNA binding domains, respectively, of DExD\/H-box helicase 58 (DDX58) encoding the RNA sensor retinoic acid inducible gene 1 (RIG-I). These variants significantly impair the signalling activity of RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG-I ligands as well as increased proinflammatory responses to IAV, suggesting dysregulation of the innate immune response with increased immunopathology. We suggest that these RIG-I variants may have contributed to severe influenza in this patient and advocate that RIG-I variants should be sought in future studies of genetic factors influencing single-stranded RNA virus infections.<\/jats:p>","DOI":"10.1111\/cei.13120","type":"journal-article","created":{"date-parts":[[2018,2,17]],"date-time":"2018-02-17T10:32:46Z","timestamp":1518863566000},"page":"366-376","source":"Crossref","is-referenced-by-count":46,"title":["Defective RNA sensing by RIG-I in severe influenza virus infection"],"prefix":"10.1093","volume":"192","author":[{"given":"S E","family":"J\u00f8rgensen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L B","family":"Ry\u00f8","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H H","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gjedsted","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Staeheli","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J G","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Storgaard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-9704","authenticated-orcid":false,"given":"T H","family":"Mogensen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Biomedicine, Aarhus University, Aarhus, 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