HCV core, NS3, NS5A and NS5B proteins modulate cell proliferation independently from p53 expression in hepatocarcinoma cell lines

Several reports have shown that activity and/or expression of p53 can be modulated by Hepatitis C virus (HCV) proteins and may interfere with normal regulation of cell growth. In order to understand the relationship between p53 function and HCV proteins expression, we have investigated potential effects of the core, NS3, NS5A and NS5B proteins on Huh-7 (p53 +/+) and Hep3B (p53 -/-) cell proliferation. The effect of HCV proteins transiently expressed after recombinant-adenoviral infection was analyzed by Western blot, crystal violet and propidium iodide staining. Expression of the core, NS3, NS5A or NS5B proteins inhibited cell proliferation and blocked both cell lines in the G2/M phase of the cell cycle. c-myc and p53 expression were respectively induced and increased in Huh-7 cells only following expression of the Core protein. No expression of p21(waf1/cip1) could be detected and expression of cyclin A, cdk2 and p27(Kip1) were independent of HCV protein's expression. Our results show that the effect of core, NS3, NS5A and NS5B on cell proliferation is independent of p53 expression and that only the Core protein, induces the expression of both c-myc and p53.