{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:14:53Z","timestamp":1790705693454,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31672534"],"award-info":[{"award-number":["31672534"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis E virus (HEV) causes predominantly acute and self-limiting hepatitis. However, in HEV-infected pregnant women, the case fatality rate because of fulminant hepatitis can be up to 30%. HEV infection is zoonotic for some genotypes. The HEV genome contains three open reading frames: ORF1 encodes the non-structural polyprotein involved in viral RNA replication; ORF2 encodes the capsid protein; ORF3 encodes a small multifunctional protein. Interferons (IFNs) play a significant role in the early stage of the host antiviral response. In this study, we discovered that the capsid protein antagonizes IFN induction. Mechanistically, the capsid protein blocked the phosphorylation of IFN regulatory factor 3 (IRF3) via interaction with the multiprotein complex consisting of mitochondrial antiviral-signaling protein (MAVS), TANK-binding kinase 1 (TBK1), and IRF3. The N-terminal domain of the capsid protein was found to be responsible for the inhibition of IRF3 activation. Further study showed that the arginine-rich-motif in the N-terminal domain is indispensable for the inhibition as mutations of any of the arginine residues abolished the blockage of IRF3 phosphorylation. These results provide further insight into HEV interference with the host innate immunity.<\/jats:p>","DOI":"10.3390\/v11111050","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T04:07:07Z","timestamp":1573531627000},"page":"1050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The Capsid Protein of Hepatitis E Virus Inhibits Interferon Induction via Its N-Terminal Arginine-Rich Motif"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0835-5554","authenticated-orcid":false,"given":"Shaoli","family":"Lin","sequence":"first","affiliation":[{"name":"Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglin","family":"Yang","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20740, USA"},{"name":"Department of General Practice, Nanjing Medical University, Nanjing 210006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4442-8004","authenticated-orcid":false,"given":"Yuchen","family":"Nan","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20740, USA"},{"name":"College of Veterinary Medicine, Northeast A&amp;F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexu","family":"Ma","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9527-6015","authenticated-orcid":false,"given":"Liping","family":"Yang","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5847-3260","authenticated-orcid":false,"given":"Yan-Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17086","DOI":"10.1038\/nrdp.2017.86","article-title":"Hepatitis E virus infection","volume":"3","author":"Kamar","year":"2017","journal-title":"Nat. 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