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Currently, the mechanisms of HEV replication and pathogenesis remain poorly understood. The innate immune response acts as the first line of defense during viral infection. The retinoic acid-inducible gene I (RIG-I)-mediated interferon (IFN) response has been implicated in establishing antiviral response during HEV infection, although the HEV RNA motifs that are recognized by RIG-I are unknown. This study identified that the U-rich region in the 3\u2032 untranslated region (UTR) of the HEV genome acts as a potent RIG-I agonist compared to the HEV 5\u2032 UTR. We further revealed that the HEV RNA pathogen-associated motif patterns (PAMPs) induced a differential IFN response in a cell type-dependent manner: a predominantly type III IFN response in hepatocytes, and a predominantly type I IFN response in enterocytes. These data demonstrate the complexity by which both host and viral factors influence the IFN response during HEV infection.<\/jats:p>","DOI":"10.1128\/mbio.03103-19","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T12:41:57Z","timestamp":1578919317000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["The U-Rich Untranslated Region of the Hepatitis E Virus Induces Differential Type I and Type III Interferon Responses in a Host Cell-Dependent Manner"],"prefix":"10.1128","volume":"11","author":[{"given":"Harini","family":"Sooryanarain","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie L.","family":"Heffron","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Jin","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.000115"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2018.11.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2013.08.009"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1338113"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2014.07.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.07.010"},{"key":"e_1_3_3_8_2","unstructured":"WHO. 2019 . 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