抄録
Hepatitis C virus (HCV) infection causes a variety of liver diseases, e.g. chronic hepatitis, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) . Several studies using transgenic mice and/or animal cell culture systems have shown a correlation between HCV proteins and hepatocellular carcinogenesis, especially between the HCV core protein and HCC. The core protein is also associated with signal transduction and apoptosis in infected cells. HCV genotype lb core protein interacts with tumor necrosis factor receptor I (TNFRI), resulting in enhancement of apoptosis. In this study we investi-gated whether variations in the core gene were correlated with hepatocellular carcinogenesis in HCV-infected patients. Using RT-PCR we amplified HCV core cDNA from sera of patients classified into two groups [11 with HCC and 10 with LC without HCC], and sequenced these samples. We found that the core sequence was highly conserved, except in four hot spots. All isolates had amino acid variations in these regions. The hot spots were located in the protein-protein interaction domain, suggesting possible effects on signal transduction. However specific patterns of sequence variation were not observed in each group, indicating no correlation between the HCV core sequence and hepatocellular carcinogenesis. We used a GST-pull down assay to analyze the interaction between HCV core proteins derived from infected patients and several TNF receptor families. We investigated three different HCV core genotypes. All interacted with TNFRI, TNFRII, lymphotoxin-β receptor, Fas, but not with CD40. These results indicate that the HCV core proteins of all isolates may have similar carcinogenic potential, and similar effects on regulation of apoptosis and/or signal transduction in cells.
