Hepatitis C Virus Research

An estimated 170 million people worldwide are infected with HCV, the leading cause of non-A, non-B hepatitis. Although infection stimulates a potent immune response, chronicity is a hallmark of HCV. Individuals who harbor persistent HCV infection are at significant risk for developing liver cirrhosis and hepatocellular carcinoma. Unfortunately, there is no existing vaccine for HCV and the majority of patients do not respond favorably to current therapy with ribavirin and IFN. To develop novel strategies for HCV control, a deeper understanding of this virus is essential.

The molecular mechanisms mediating liver tropism and HCV gene expression and genome replication in infected liver cells are poorly understood. A salient characteristic of the HCV genome is the presence of an internal ribosomal entry site (IRES) that is absolutely required for initiation of translation and subsequent genome replication. Significant efforts have been directed toward characterization of HCV IRES-mediated translation initiation, partly because the HCV IRES presents an attractive target for antiviral therapy. However, a role for specific cis-acting HCV RNA elements in translation control is controversial and the function of trans-acting cellular proteins in this process remains obscure. We are examining the molecular mechanism of translation initiation at the HCV IRES and its modulation by cis-acting genomic elements as well as eukaryotic trans-activators. We utilize a novel cell-based reporter expression approach that takes into account the complex involvement of viral and cellular determinants in translation control at the IRES. In addition, we are analyzing chimeric picornaviruses under translational control of the HCV IRES in cell culture and mice. Our research is yielding insight into the mechanisms that determine HCV gene expression, viral genome stability and tissue type specificity for hepatic cells. For more information on HCV and other hepatitis viruses, visit the CDC viral hepatitis website

Duke University Medical Center
Jones 453
Research Drive
Durham,NC 27710

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