Associations among Genotype 1b Hepatitis C Virus Core Protein, Protein Kinase R, and Signal Transducer and Activator of Transcription 3
Hepatitis Monthly: ,
10 (4); 275-284 Article Type: Research Article
February 10, 2010
September 17, 2010
C. Associations among Genotype 1b Hepatitis C Virus Core Protein, Protein Kinase R, and Signal Transducer and Activator of Transcription 3,
Online ahead of Print
Background and Aims: Because hepatitis C virus (HCV) core protein (Core), protein kinase R (PKR), and signal transducer and activator of transcription 3 (STAT3) all play relevant roles in the pathogenesis of HCV, persistent infection and hepatocellular carcinoma (HCC) and PKR may interact with HCV Core. In this study, we further investigate the associations among HCV Core, PKR, and STAT3 and the mechanisms involved in these interactions. Materials and 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 harboring the full length of genotype 1b HCV genomes. Co-immunoprecipitation and glutathione S-transferase (GST) pull-down assay were conducted for HCV Core, PKR, and STAT3. Results: HCV may have induced the expression of STAT3 and the activity of PKR (p-eIF-2α). HCV Core, STAT3, and PKR appear to have interacted with one another. The N-terminal 1-126 amino acid (aa) of HCV Core contributed to an interaction between HCV Core and STAT3, and only full-length PKR bound to STAT3 and p-STAT3. Conclusions: These findings suggest that HCV Core, PKR, and STAT3 can interact with each other. Specifically, HCV Core may play its role through both PKR and STAT3. Alternatively, HCV Core's binding to and activation of STAT3 might be due to the interaction between HCV Core and PKR. The distinct interactions among these three molecules are important and may reveal a new molecular mechanism in the pathogenesis of HCV-persistent infection and HCV-related HCC.
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