Studying the Hepatitis C Virus-Induced Epigenetic Signature After Cure with Direct-Acting Antivirals

: Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC). While direct-acting antiviral (DAA) therapy efficiently eradicates HCV infection, epidemiological studies show that sustained virological response (SVR) following anti-HCV treatment reduces, but does not eliminate, the risk for HCC. We have recently demonstrated that HCV infection induces genome-wide epigenetic changes that reprogram host gene expression and persist as "epigenetic signature" following virus eradication by DAAs. We suggest that this epigenetic signature underlie the residual risk for HCC post-SVR. Here, we provide a methodology to study the HCV-induced epigenetic signature. We describe a ChIP-seq protocol to evaluate changes in epigenome profile following HCV infection, its cure with DAA, and after treatment with epigenetic modifier inhibitor. We also describe evaluation of changes in the gene expression profile using RNA-seq. The integration between detected alterations in epigenetic marks and gene expression allows for identification of biological processes that are involved in HCV-driven oncogenesis before and after cure.