Infection with HCV is the foremost cause of liver disease in the United States. The current anti-HCV treatments are insufficient, and a protective vaccine is not available. The Pager laboratory is fascinated by virus-host interactions. We are particularly interested in how Hepatitis C virus (HCV) interacts with and manipulates host mRNA metabolism. For example: to synthesize viral proteins, HCV uses a RNA element known as an internal ribosome entry site or IRES, at the start of the viral genome to recruit cellular ribosomes and a subset of translation factors. Furthermore, HCV uniquely interacts with the liver-specific microRNA miR-122 to maintain the levels of viral RNA. We recently discovered that a number of cellular factors found in RNA granules are critical for HCV gene expression, and that the virus specifically recruits these factors to sites where the virus assembles. Curiously many of these RNA granule factors are involved in microRNA-mediated gene regulation, mRNA storage and mRNA degradation. Our current research focuses on understanding how and why HCV exploits these factors for virus gene expression. We use methods in virology, biochemistry, RNA biology, cell biology and microscopy to determine the importance and function of these factors at each step in the HCV lifecycle; RNA granule-HCV interactions; and the protein and RNA modifications that occur during HCV infection. By understanding the HCV lifecycle and virus-host interactions our ultimate goal is identify and develop novel anti-HCV targets.