Grant: CIHR Fellowship

In spite of the considerable work in the hepatitis C virus (HCV) field there are still many questions that remain unanswered regarding the HCV life cycle. Currently, over 170 million individuals are infected with HCV worldwide and about 300,000 HCV infected individuals live in Canada. The only treatment currently licensed to treat chronic HCV carriers is a combination of pegylated interferon alpha (IFN-alpha) and ribavirin. This treatment is only successful in 50-55% of the patients infected by genotype 1, the genotype most common in infected patients. Two new protease inhibitors have been licensed in the US and will be licensed in Canada and worldwide. However, early indications are that they will be very expensive which will limit their access to many patients. In addition, HCV replication has a lower fidelity than many viruses making the emergence of resistance a serious potential problem. The rapid generation of the viral mutation makes it harder to identify good viral targets for treatment. Therefore, studying of interactions between viral proteins and the host proteins, which are crucial for the viral life cycle, may lead to better understanding of the infection cycle and to the discovery of new targets for anti-HCV drug development which are less susceptible to mutations and antiviral resistance. In this study we are going to characterize the novel interactions of HCV proteins that are responsible for the recruitment of the host Nucleoporins proteins to the viral replication sites. In addition we will try to identify peptides which specifically interrupt these interactions. These studies may be used to develop lead compounds for novel anti-HCV drug development. This work will lead to a better understanding of the HCV replication and possibly lead to new ways to defeat the virus.