Grant: Project Grant

Hepatitis C virus (HCV) infection is a global health problem that affects 71 million people worldwide, including over 250,000 Canadians. HCV-infected individuals typically develop a persistent infection that leads to chronic hepatitis, cirrhosis, steatosis and liver cancer. Currently, there is no vaccine available and although effective antiviral treatments exist, cost and treatment accessibility remain barriers to HCV elimination. To establish an infection, HCV commanders may different factors in our cells. In healthy cells, small molecules, called microRNAs, restrict how much our genes are expressed. HCV co-opts a liver-specific microRNA and uses it to amplify itself. Clinical trials using inhibitors of the microRNA, revealed that preventing the virus from accessing this microRNA may be an effective treatment option. We have preliminary evidence that suggests that HCV uses this microRNA to promote viral protein production, genome stability, and we hypothesize that the microRNA also helps the virus to establish replication factories where progeny viruses are produced. The focus of this research is to investigate how HCV uses the microRNA to its own benefit and to identify other human factors that the virus uses to amplify itself in the liver. This research will provide us with insight into mechanisms of microRNA-mediated enhancement of viral replication and may reveal novel antiviral targets. Moreover, the mechanism(s) used by HCV to establish viral replication factories may be applicable to a wide range of viruses that impact human health. Thus, not only will this work improve our understanding of HCV infection, but the outcomes may help us to understand microRNA function, replication of a wide range of viruses, and is likely to provide new approaches for antiviral intervention for a number of important human pathogens