Grant: Operating Grant

Hepatitis C virus (HCV) is one of the most common blood-born human pathogens which causes chronic liver inflammation, called hepatitis C. Complications of this infection, such as liver cirrhosis and cancer, are currently the main indications for liver transplantation. In Canada, estimated 250,000 people are chronically infected HCV, but many others are unaware that they are infected. The virus infects not only the liver, but also the host's immune (lymphatic) system. We were among those who first discovered that HCV also infects human immune cells and have established the system in which the patient-derived virus can infect these cells in culture. We also identified molecules essential for HCV infection of human T lymphocytes. In addition, we uncovered that HCV replication persists for a very long time in both liver and immune system after termination of a symptomatic disease. Our findings are entirely original and they are of significant clinical and epidemiological importance. In further studies, we want to determine the molecular and biophysical properties of HCV that infects and replicates in the human immune cells, uncover mechanisms underlying virus ability to infect different subsets of these cells, and recognize the virus potential contribution to the development of proliferative (cancerous) diseases of the lymphatic system, such as lymphomas. Our research should generate new information on the nature of HCV lymphotropism and the mechanisms of HCV life-long persistence. It also should create base for the development of new antivirals targeting HCV at the extrahepatic sites of replication.