The Effect Of Interferon-stimulated Gene 12a (ISG12a) On Hepatitis C Virus Replication And Its Mechanism

Interferon stimulated(sensitive)genes(ISGs)are the effector molecules downstream of type ?/? interferon(IFN)signaling pathways in host innate immunity.ISG12a can be induced by IFN-?.Although ISG12a has been reported to inhibit the replication of HCV,the exact mechanism remains to be determined.In this study,we investigated the possible mechanisms of ISG12a anti-HCV property by exploring the production of type I IFN and the activation of Janus kinase/signal transducer and activator of transcription(Jak/STAT)signaling pathway,apoptosis,autophagy and the interaction between ISG12a and USP 18 in Huh7.5.1 cells transiently transfected with ISG12a over-expression plasmid.Interestingly,we found that ISG12a inhibited HCV replication in both Conlb replicon and the HCV JFH1-based cell culture system and potentiated the anti-HCV activity of IFN-a.ISG12a promoted the production of IFN a/? and activated the type I IFN signaling pathway as shown by increased p-STAT1 level,higher Interferon sensitive response element(ISRE)activity and up-regulated ISG levels.However,ISG12a over-expression did not affect cell autophagy,apoptosis and have the interaction between ISG12a and USP 18.Data from our current study collectively indicated that ISG12a inhibited HCV replication and potentiated the anti-HCV activity of IFN-a possibly through induced production of type I IFNs and activation of Jak/STAT signaling pathway independent of autophagy,cell apoptosis and the interaction between ISG12a and USP 18.