T cell mediated evolution of the hepatitis C virus during acute infection. (360G-Wellcome-102789_Z_13_Z)

Globally, 170 million people are infected with hepatitis C virus (HCV). A vaccine and new treatment strategies for are therefore highly desirable. Much work on the mechanisms underlying spontaneous control of HCV (15-50% of those infected) has been carried out, but this has been based on small patient groups (typically 10-20 individuals) as early HCV infection rarely presents clinically. Small human and animal studies have highlighted the role of the T-cell response in spontaneous clearance. I now have the opportunity to investigate the determinants of spontaneous clearance and progression to chronicity in a large well-characterised cohort of patients with acute HCV infection. The key research goals of this project are to identify conserved and variable regions of the HCV genome during early infection, to characterise the phenotype, specificity and function of T-cells during evolving spontaneous clearance and to correlate changes within the viral quasispecies with adaptive immune res ponses over time. I will use deep sequencing to amplify the whole HCV genome and will link changes in viral population structure with T cell responses using flow cytometry, ELISpot analysis and the HCV replicon system.