Grant: Catalyst Grant:Infection & Immunity-PHAC-CAID/Hep C Res Init/Biomed/clin stream

Hepatitis C (HCV) is a major cause of serious health problems worldwide and in Canada with approximately 200 million people worldwide carrying the virus. The majority (70-80%) of individuals to become infected with HCV develop a chronic infection with HCV that can lead to chronic active hepatitis, cirrhosis and hepatocellular carcinoma. Studies of the immune response to HCV have been severely hampered by the lack of tissue culture and small animal models of HCV infection. However, both the innate and adaptive immune response are thought to play a critical role in control and clearance of HCV in those patients that evade chronic infection. Epidemiological studies have linked resistance to chronic HCV infection with Killer Cell Immunoglobulin-like Receptors (KIR), a diverse family of polymorphic receptors that regulate natural killer cell responses. Although the virus was discovered in 1989, it has been very difficult to study the immune response to this virus because the virus could not be replicated in tissue culture in laboratories. The studies outlined in this proposal will exploit a recently developed method to infect liver cells in the laboratory with HCV in order to study how natural killer cells respond to the infected cells and how the natural killer cells are able to suppress replication of the virus. The results of these studies will aid the design of immuno-therapies developed to cure HCV by exploiting the innate properties of natural killer cells.