Grant: Banting Postdoctoral Fellowship Program

Although there has been considerable work in the hepatitis C virus (HCV) field, there are still many unanswered questions regarding the HCV life cycle. HCV infects over 300,000 Canadians and 170 million individuals worldwide and it is the major cause of liver disease including liver cancer. About 5,000 to 10,000 Canadians are newly infected each year and approximately 1,000 deaths due to HCV occur annually in Canada. Until recently the only licensed treatment was a combination of pegylated interferon alpha (IFN-alpha) and ribavirin which was successful in only 45 to 50% of the patients infected by genotype 1, the genotype which is most commonly found in infected patients. A new oral anti-viral drug targeted to the HCV protease has increased the success rate for treatment to 75%, but this therapy is associated with significant side effects and is very expensive. There is a need for additional new anti-viral drugs. The high rate of mutations in the virus during its life cycle leads to rapid growth of resistance to most new drugs targeting viral proteins. Therefore, the study of interactions between viral proteins and host proteins, which are required for the viral life cycle, may result in a better understanding of the infection cycle. This research may also discover new targets for improved anti-HCV drugs that may be less affected by virus mutations. In this work we are going to study the novel interactions of HCV proteins that are responsible for the recruitment of the host nucleoporins proteins to the replication sites in the infected cell. In this research, we will try to develop peptides to specifically interrupt interactions of particular viral and host proteins (nucleoporins) which may be used as a lead compound for novel anti-HCV drug development. This work will give us a better understanding of HCV life cycle and will provide us with more possibilities for improved drugs to defeat the virus.