Mutational escape from cellular immunity in viral hepatitis: variations on a theme

Approx. 320 million individuals worldwide are chronically infected with hepatitis viruses, contributing to viral hepatitis being one of the 10 leading causes of death. Cellular adaptive immunity, namely CD4+ and CD8+ T cells, plays an important role in viral clearance and control. Two main mechanisms, however, may lead to failure of the virus-specific T-cell response: T-cell exhaustion and mutational viral escape. Viral escape has been studied in detail in hepatitis C virus (HCV) infection, where it is thought to affect approx. 50% of virus-specific CD8+ T-cell responses in persistent infection, to influence natural infection outcome and to contribute to failure of preventive vaccination strategies. In hepatitis B virus (HBV) as well as HBV/hepatitis D virus (HDV) co-infection, the impact of viral escape has been studied in detail only recently.