Hepatitis C virus core protein interacts with 14-3-3 protein and activatesthe kinase Raf-1

Persistent hepatitis C virus (HCV) infection is a major cause of chronic li ver dysfunction in humans and is epidemiologically protein has been reporte d to be implicated in cell growth regulation both in vitro and in vivo, alt hough mechanisms explaining those effects are still unclear. In the present study, we identified that members of the 14-3-3 protein family associate w ith HCV core protein. 14-3-3 protein bound to HCV core protein in a phospho serine-dependent manner, Introduction of HCV core protein caused a substant ial increase in Raf-1 kinase activity in HepG2 cells and in a yeast genetic assay. Furthermore, the HCV core-14-3-3 interaction was essential for Raf- 1 kinase activation by HCV core protein. These results suggest that HCV cor e protein may represent a novel type of Raf-1 kinase-activating protein thr ough its interaction with 14-3-3 protein and may contribute to hepatocyte g rowth regulation.