Grant: Operating Grant

Approximately 300,000 Canadians are currently infected with the hepatitis C virus, and as many as 80,000 of these people may not yet know it. Up to 70% of these individuals will progress to develop liver cirrhosis, and some will go on to develop hepatocellular carcinoma. Currently available therapies show limited efficacy with uncomfortable side-effects and poor tolerance. Treatment for this large number of people will translate to an enormous impact on public health in our country. The main focus of my research will be to identify novel targets for anti-HCV therapy, and it is my hope that these efforts will contribute to the development of novel antiviral drugs to help fight this disease. Until recently there was no robust cell culture system available for the study of HCV, but in 2005 a fully infectious HCV cell culture system was established that allows secretion of infectious virus particles upon transfection of human hepatocyte cell lines. Using this system, it is now possible to study all aspects of the viral life cycle, including virus entry and assembly, as well as the role of critical cellular factors in these processes. Presumably, HCV particle formation is driven by the core structural protein. At some point, either during or after core has assembled a genome-containing capsid, viral glycoproteins E1 and E2 are incorporated into the virion. Using the infectious HCV system, I plan to characterize the role of the viral core protein in the virion assembly process. My previous work suggests that the viral p7 and NS2 proteins also contribute in some way to the virus assembly process. I plan to elucidate the mechanisms by which these proteins play a role in virus assembly and production of infectious virions. The information obtained from these studies will not only contribute to the basic understanding of the HCV life cycle, but will also help to identify putative new targets for specific antiviral therapy.