Viral and Host Factors in Chronic Hepatits C Infection

Hepatitis C virus (HCV) infection is a serious global public health problem affecting more than 170 million people. The majority of infected individuals go on to develop chronic infection ultimately resulting in cirrhosis and possibly liver cancer. There is no vaccine available for hepatitis C and current treatment options are limited by the necessity of long treatment duration and severe side effects. Despite major advances in understanding of what constitutes an effective immune response in those individuals who resolve the acute viral hepatitis infection and how the immune system fails in those who are chronically infected, many questions remain to be answered. The impact of hepatitis C viral factors, such as mutation rates and patterns and viral replication capacity on disease progression and response to therapy is not well understood. We therefore aim to study the evolution of viral factors and host immunity in chronic HCV infection in different body compartments (liver versus blood). Specific aims of our study are: a) To study the impact of compartmentalization (liver versus blood) on viral mutation patterns and quasispecies formation b) To study the impact of MHC class I restricted immune responses in liver versus blood on viral factors such as mutation patterns and replicative capacity c) To study the role of viral replicative capacity in liver disease progression and response to anti-viral treatment We will try to answer these questions with patient derived liver and blood samples using state-of-the-art virological and immunological laboratory methods. Understanding the correlates of immune protection will contribute to the development of better immuno-therapies or a preventive vaccine for HCV. The proposed project will allow me to master laboratory skills relating to the study of chronic viral illnesses and to ultimately become an independent translational investigator. By complementing my clinical training with hypothesis driven bench research I hope to be able to practice as a clinician-scientist in Austria in the future while maintaining strong international collaborations.