Hepatitis C virus-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in hepatocytes

We have established monoclonal antibodies (MoAbs) that are directed against hepatitis C virus (HCV)-expressing cells. They showed enhanced tumorigenicity after passage in culture for more than 44 days (RzM6-44d cells). To address the mechanism underlying this phenomenon, we characterized the MoAbs, and found that one of the clones recognized a molecule that was down-regulated in the RzM6-44d cells. This molecule was purified and identified as the 70-kDa thyroid autoantigen Ku70. Moreover, expression of the full-length HCV genome or HCV-core protein sequence in WRL68 human embryonic liver cells reduced the level of Ku70 protein, enhanced the ubiquitination of Ku70, and decreased the activity of DNA-activated protein kinase (DNA-PK). Therefore, it appears that the HCV-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in noncancerous liver cells.