Effect of P‐body component Mov10 on HCV virus production and infectivity

摘要

titleAbstract/titlepMov10 is a processing body (P‐body) protein and an interferon‐stimulated gene that can affect replication of retroviruses, hepatitis B virus, and hepatitis C virus (HCV). The mechanism of HCV inhibition by Mov10 is unknown. Here, we investigate the effect of Mov10 on HCV infection and determine the virus life cycle steps affected by changes in Mov10 overexpression. Mov10 overexpression suppresses HCV RNA in both infectious virus and subgenomic replicon systems. Additionally, Mov10 overexpression decreases the infectivity of released virus, unlike control P‐body protein DCP1a that has no effect on HCV RNA production or infectivity of progeny virus. Confocal imaging of uninfected cells shows endogenous Mov10 localized at P‐bodies. However, in HCV‐infected cells, Mov10 localizes in circular structures surrounding cytoplasmic lipid droplets with NS5A and core protein. Mutagenesis experiments show that the RNA binding activity of Mov10 is required for HCV inhibition, while its P‐body localization, helicase, and ATP‐binding functions are not required. Unexpectedly, endogenous Mov10 promotes HCV replication, as CRISPR‐Cas9‐based Mov10 depletion decreases HCV replication and infection levels. Our data reveal an important and complex role for Mov10 in HCV replication, which can be perturbed by excess or insufficient Mov10./p