Hepatitis C virus core protein enhances p53 function through augmentation of DNA binding affinity and transcriptional ability

Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, a nd hepatocellular carcinoma. Since there are several reports indicating tha t some viruses influence the tumor suppressor p53 function, we determined t he effects of MCV proteins on p53 function and its mechanism determined by use of a reporter assay. Among seven HCV proteins investigated (core, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), only core protein augmented the transcrip tional activity of p53 and increased the expression of p21(waf1) protein, w hich is a major target of p53. Core protein increased both DNA-binding affi nity of p53 in electrophoretic morbidity shift assay and transcriptional ab ility of p53 itself in a reporter assay. The direct interaction between cor e protein and C terminus of p53 was also shown by glutathione S-transferase fusion protein binding assay. In addition, core protein interacted with hT AF(II)28, a component of the transcriptional factor complex in vivo and in vitro. These results suggest that HCV core protein interacts with p53 and m odulates p53-dependent promoter activities during HCV infection.