Associations Among Genotype 1b Hepatitis C Virus Core Protein, Protein Kinase R And Signal Transducer And Activator Of Transcription 3

AIM Since hepatitis C virus (HCV) core protein (Core), protein kinase R (PKR) and signal transducer and activator of transcription 3 (STAT3) all play a relevant role in the pathogenesis of HCV persistent infection and hepatocellular carcinoma (HCC), and PKR could interact with Core. Here we further investigate the associations among Core and STAT3 and PKR, and and the domains of them involved in the interactions. Methods Expression levels of HCV Core, PKR, eukaryotic initiation factor 2 (eIF-2α), phosphorylated eIF-2α (p-eIF-2α), STAT3 and phosphorylated-STAT3 (p-STAT3) were compared between Huh-7 and replicon cell-Huh-7 cells harbouring selecting full-length of genotype 1b HCV genomes. Co-immunoprecipitation and glutathione S-transferase (GST) pull-down assay were done among PKR, STAT3 and Core. Results HCV could induce the expression of STAT3 and the activity of PKR (p-eIF-2α). Either of Core, STAT3 and PKR can interact with one another. The N-terminal 1-126 amino acid (aa) of HCV Core contributed to Core/STAT3 interaction and only the full-length of PKR binds to STAT3 and p-STAT3. Conclusions These findings suggest that Core, PKR and STAT3 can interact with each other. Core plays its function through both of PKR and STAT3; or Core binding to STAT3 and activating STAT3 might be due to Core/PKR interaction. The distinct interactions among them might play an important role and provide a new molecular mechanism in the pathogenesis of HCV persistent infection and HCV-related HCC