MxA is a Positive Regulator of Type I IFN Signaling in HCV Infection.

Type I interferons (IFNs) are a family of primordial cytokines that respond to various pathogen infections including Hepatitis C virus (HCV). Type I IFNs signal through Jak/STAT pathway leading to the production of a few hundred interferon stimulated genes (ISGs). The aim of this study was to explore the role of one of these ISGs, MxA in HCV infection and type I IFN production. Plasmid encoding MxA was cloned into PcDNA3.1‐3×tag vector and MxA expression was confirmed both at mRNA (RT‐PCR) and protein (Western blot, WB) levels. IFNα and IFNβ productions were quantified by RT‐PCR from cell lysate and by ELISA kit from culture medium following MxA over‐expression in Huh7.5.1 cells. The activation status of Jak/STAT signaling pathway was examined at three levels: p‐STAT1 (WB), interferon sensitive response element (ISRE) activity (dual luciferase reporter gene assay), and levels of ISG expression (RT‐qPCR). J6/JFH1 HCV culture system was used to study the role of MxA in HCV replication. Our findings indicated that MxA over‐expression inhibited HCV replication and potentiated the IFNα‐mediated anti‐HCV activity; MxA stimulated the production of IFNα, IFNβ, and enhanced IFNα‐induced activation of Jak‐STAT signaling pathway. We concluded that MxA is a positive regulator of type I IFN signaling in HCV infection.