Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein

Hepatitis C virus (HCV) is a major etiological agent of chronic liver disea se and hepatocellular carcinoma (HCC). We demonstrate herewith that HCV cor e proteins encoded by sequences isolated from HCC tumor tissues, but not th ose derived from their non-tumor counterparts in the same liver, co-localis e in vitro and in vivo and co-immunoprecipitate with PKR in hepatocytic Huh 7 cells. We show that this association in fact augments the autophosphoryla tion of PKR and the phosphorylation of the translation initiation factor eI F2 alpha, which are two markers of PKR activity. The present study therefor e identifies a novel model of virus-cell interactions whereby a viral prote in, the HCV core, activates PKR activity.