Grant: Master's Award: Canada Graduate Scholarships

Hepatitis C virus (HCV) infects nearly 170 million people worldwide. Approximately 250,000 Canadians are infected with HCV, with as many as 5,000 new cases per year. The human immune system is unable to effectively clear this virus, thus HCV establishes persistent infection in roughly 70% of exposed individuals. Over time, persistent infection leads to liver scarring (fibrosis and cirrhosis) and in some cases, liver cancer (hepatocellular carcinoma). Viruses, including HCV, employ numerous mechanisms to avoid immune responses and establish chronic infection. One possible mechanism by which HCV avoids the innate immune system is by down regulating natural killer (NK) cell effector functions. As they require no previous activation, NK cells are part of the first line of defense against viral infection. Since there is no suitable animal model to study HCV infection, we adapted a cell culture system to allow in vitro study of the effect this virus has on immune function, in particular NK cell function. Our first results suggest that HCV selectively represses NK cell function. Further development of this cell culture system will not only allow direct study of the effect HCV has on NK cells, but will also allow study of the effect this virus has on other immune cell subsets. This research will lead to a better understanding of how HCV can fight back against immune responses to establish persistent infection and also to greater understanding of the actual mechanism by which HCV turns off the NK cell's ability to destroy virus-infected cells. Greater knowledge in these areas will aid the quest for a vaccine more effective treatment against this virus.