Limin Chen
University of Toronto, Canada
Title: Novel insights into the molecular mechanisms of interferon resistance of hepatitis C and B viruses based on gene expression profiling
Biography
Biography: Limin Chen
Abstract
Hepatitis viruses, including Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infect human liver leading to chronic infections that gradually develop into cirrhosis and hepatocellular carcinoma (HCC). Current treatment regimen includes interferon and nucleotide analogues (NAs). Although direct acting anti-viral agents (DAAs) clear the virus in more than 95% individuals chronically infected with HCV, pegylated interferon is still widely used in many asia countries. Unfortunately, not all patients chronically infected with HCV respond to pegylated interferon/ribavirin combination therapy. As such, understanding the molecular mechanisms of interferon resistance of HCV and HBV is essential for better management of patients. Based on gene expresion profiling, we identified an 18-gene response signature that can be used to predict whether a given patients will respond to interterferon-based therapy with an accuracy of 96%. A novel ubiquitin-like ISG15/USP18 signaling pathway was also identifed to be involved in interferon resistance in both HCV and HBV infections. A series of functional studies onISG15 and USP18 genes revealed the detailed molecualr mechanisms of interferon resistance of HBV and HCV. Data from our studies indicated that ISG15(and ISG15 conjugation-the process called ISGylation) stimulated HCV replication and potentiated the interferon anti-HCV activity. Silencing of USP18 boosts the antiviral activity of interferon against hepatitis C virus infection through activation of the Jak/STAT signaling in vitro HCV culture (HCVcc) model.
