Various miRNAs are involved in efficient HCV replication

Abstract

17One of the determinants for tissue tropism of hepatitis C virus (HCV) is miR-122, a liver-specific 18 microRNA. Recently, it has been reported that interaction of miR-122 to HCV RNA induces a 19 conformational change of the 5'UTR internal ribosome entry site (IRES) structure to form stem-loop II 20 structure (SLII) and hijack of translating 80S ribosome through the binding of SLIII to 40S subunit, 21 which leads to efficient translation. On the other hand, low levels of HCV-RNA replication have also 22 45 3 both G28 and C29 in the 5'UTR. The interaction of these non-hepatic miRNAs with the 5'UTR can 46 facilitate not only the folding of active HCV IRES but also the stabilization of IRES 3D structure in 47 order to facilitate binding to the ribosome. These results suggest the possibility of replication of HCV in 48 non-hepatic cells through interaction with miRNAs other than miR-122 and provide insight into the 49 establishment of persistent infection of HCV in non-hepatic tissues that lead to the development of 50 extrahepatic manifestations. 51 52