Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals

by Shira Perez, Antony Kaspi, Tom Domovitz, Ateret Davidovich, Anat Lavi-Itzkovitz, Tomer Meirson, Jacinta Alison Holmes, Chia-Yen Dai, Chung-Feng Huang, Raymond T. Chung, Assy Nimer, Assam El-Osta, Gur Yaari, Salomon M. Stemmer, Ming-Lung Yu, Izhak Haviv, Meital Gal-Tanamy The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigeneti c markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the vi ral proteins in the cell...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research