Defining host and viral factors that are associated with hepatitis B virus control and clearance in Caucasian and African adults. (360G-Wellcome-110110_Z_15_Z)

HBV accounts for a significant global burden of liver disease. This project is founded on the urgent need to characterise T cell responses in order to enhance our understanding of differential outcomes of infection, and underpin future immunotherapeutic strategies. I will recruit a multi-centre cohort of adults with chronic hepatitis B infection (CHB) in Africa and the UK, to study factors associated with immune containment of HBV. Viral activity will be assessed using serum markers (HBeAg s tatus, HBsAg level, HBV DNA viral load). I will undertake deep sequencing of full length virus, first to identify patterns of selection of viral polymorphisms, and then to correlate these with changes in these biomarkers. Secondly, as CD8+ T cells may contribute to HBV suppression, I will use a computational algorithm to identify sites of HLA Class I mediated selection in HBV. These footprints can be used to identify sites of novel T cell epitopes and to identify polymorphisms that may impact on viral fitness. I will assess the impact of host factors that may have influence on this immunological containment, including age, gender and HIV co-infection. Overall, these data will provide unique insights into HBV immune control.