Hepatitis C Virus Derived Small RNA, vmr11, Inhibits Nuclear PTEN Accumulation In Primary Human Hepatocytes Open Access
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Hepatitis C Virus (HCV) has become an epidemic in the past decade. There are more than 300 million people worldwide that are chronically infected with this virus. Its prevalence has surpassed that of HBV, and will prove to be greater burden to the health care system in coming decades. Earlier research has shown that chronic HCV infection is closely associated liver fibrosis, cirrhosis and hepatocellular carcinoma. However, molecular mechanisms leading to these conditions following HCV infection are still unclear. Here we present evidence that a novel HCV-derived small non-coding RNA, vmr11, which is expressed in HCV genotype 1a infected human primary hepatocytes, down regulates nuclear accumulation of PTEN protein leading to genomic instability. The nuclear insufficiency of PTEN in HCV infected cells results in the induction of gamma-H2Ax, a marker for DNA double-strand breaks (DSB). Overall, the results suggest a novel mechanism of HCV-infection mediated hepatocarcinogenesis that is initiated by depletion of nuclear PTEN protein and genomic instability.