{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:33:01Z","timestamp":1791549181248,"version":"4.3.4"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T00:00:00Z","timestamp":1524096000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T00:00:00Z","timestamp":1524096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>\n                    The outcomes of hepatitis E virus (HEV) infection are diverse, ranging from asymptomatic carrier, self\u2010limiting acute infection, and fulminant hepatitis to persistent infection. This is closely associated with the immunological status of the host. This study aimed to understand the innate cellular immunity as the first\u2010line defense mechanism in response to HEV infection. Phosphorylation of signal transducer and activator of transcription 1, a hallmark of the activation of antiviral interferon (IFN) response, was observed in the liver tissues of the majority of HEV\u2010infected patients but not in the liver of uninfected individuals. In cultured cell lines and primary liver organoids, we found that HEV RNA genome potently induced IFN production and antiviral response. This mechanism is conserved among different HEV strains, including genotypes 1, 3, and 7 as tested. Interestingly, single\u2010stranded HEV RNA is sufficient to trigger the antiviral response, without the requirement of viral RNA synthesis and the generation of an RNA replicative form or replicative intermediate. Surprisingly, the m\n                    <jats:sup>7<\/jats:sup>\n                    G cap and poly A tail are not required, although both are key features of the HEV genome. Mechanistically, this antiviral response occurs in a retinoic acid\u2013inducible gene\u2010I\u2013independent, melanoma differentiation\u2013associated protein 5\u2013independent, mitochondrial antiviral signaling protein\u2013independent, and \u03b2\u2010catenin\u2010independent but IRF3\u2010dependent and IRF7\u2010dependent manner. Furthermore, the integrity of the Janus kinase\u2013signal transducer and activator of transcription pathway is essentially required.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    HEV infection elicits an active IFN\u2010related antiviral response\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and in patients, triggered by the viral RNA and mediated by IFN regulatory factors 3 and 7 and the Janus kinase\u2013signal transducer and activator of transcription cascade; these findings have revealed new insights into HEV\u2013host interactions and provided the basis for understanding the pathogenesis and outcome of HEV infection. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018;67:2096\u20102112).\n                  <\/jats:p>","DOI":"10.1002\/hep.29702","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T15:00:49Z","timestamp":1512140449000},"page":"2096-2112","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":59,"title":["The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response"],"prefix":"10.1097","volume":"67","author":[{"given":"Wenshi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Hepatology,Beijing 302 Hospital,Beijing,People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbo","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Hepatology,Beijing 302 Hospital,Beijing,People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"},{"name":"State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences,Lanzhou,Gansu,People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buyun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad S.","family":"Hakim","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"},{"name":"Department of Microbiology, Faculty of Medicine,Universitas Gadjah Mada,Yogyakarta,Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebang","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiancheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Gakuen 4\u20107\u20101 Musashi\u2010murayama,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maikel P.","family":"Peppelenbosch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Hepatology,Beijing 302 Hospital,Beijing,People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuwei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Erasmus MC\u2010University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,4,19]]},"reference":[{"issue":"Suppl. 1","key":"hep29702-bib-0001-20241017","first-page":"130","article-title":"Hepatitis E, the neglected one","volume":"36","year":"2016","journal-title":"Liver Int"},{"key":"hep29702-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/QCO.0000000000000316","article-title":"Treatment of hepatitis E 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