biostudies-literatureAhmed CSIslamic DevelopmentBiotechnology and Biological Sciences Research Council6330-6343https://www.ebi.ac.uk/biostudies/studies/S-EPMC6158612biostudies-literatureUnknown46(12)Hepatitis C virus (HCV) is a positive sense RNA virus that persistently infects human liver, leading to cirrhosis and hepatocellular carcinoma. HCV replication requires the liver-specific microRNA-122 (miR-122). In contrast to canonical miRNA-mediated repression via 3'UTR sites, miR-122 positively regulates HCV replication by a direct interaction with the 5' untranslated region (UTR) of the viral RNA. The protein factor requirements for this unusual miRNA regulation remain poorly understood. Here, we identify eIF4AII, previously implicated in miRNA-mediated repression via 3'UTR sites, as a host factor that is important for HCV replication. We demonstrate that eIF4AII interacts with HCV RNA and that this interaction is miR-122-dependent. We show that effective miR-122 binding to, and regulaNucleic acids researchEukaryotic translation initiation factor 4AII contributes to microRNA-122 regulation of hepatitis C virus replication.PMC615861261/PAK/P33BB/F02360X/1Parsons ALAhmed CSWinlow PLJopling CLfalseEukaryotic translation initiation factor 4AII contributes to microRNA-122 regulation of hepatitis C virus replication.Hepatitis C virus (HCV) is a positive sense RNA virus that persistently infects human liver, leading to cirrhosis and hepatocellular carcinoma. HCV replication requires the liver-specific microRNA-122 (miR-122). In contrast to canonical miRNA-mediated repression via 3'UTR sites, miR-122 positively regulates HCV replication by a direct interaction with the 5' untranslated region (UTR) of the viral RNA. The protein factor requirements for this unusual miRNA regulation remain poorly understood. Here, we identify eIF4AII, previously implicated in miRNA-mediated repression via 3'UTR sites, as a host factor that is important for HCV replication. We demonstrate that eIF4AII interacts with HCV RNA and that this interaction is miR-122-dependent. We show that effective miR-122 binding to, and regula2018-01-01T00:00:00Z2018 Jul2026-06-11T04:13:25.849Z2019-03-26T23:58:24ZS-EPMC61586122966901410.1093/nar/gky262