Hepatitis C virus (HCV) is a globally important virus that infects 170 million individuals world wide, resulting in progressive chronic liver disease. At present, there are limited therapies available for treating hepatitis C and there is an urgent need for the development of new agents that will cure infection. Viruses initiate infection by attaching to molecules or receptors on the cell surface, providing a target for therapeutic intervention. Recent advances have identified the cellular molecules defining HCV entry into liver cells. Studies from our laboratory have shown that HCV strains differ in their interaction with host cell receptors and this will have significant consequences for virus infectivity and spread in the liver. We hypothesise that such differences in HCV-receptor interactions will influence the ?relative fitness? of a virus to transmit and infect new individuals. We will use molecular and biological methods to study transmitting HCV strains to increase our understanding of the molecular events that define and limit virus transmission.