Structure and selection of hepatitis B virus variants during the natural course of infection and interferon therapy

The consequences of hepatitis B virus (HBV) infection range from asymptomatic transient and chronic infections to mild and severe forms of hepatitis up to the development of liver cirrhosis and hepatocellular carcinoma. Immune-mediated destruction of infected liver cells plays a major role in HBV pathogenesis. Escape from immune-recognition by changing the antigenic make-up of HBV or by preventing the expression of some viral proteins leads to the emergence of viral variants. Variants can harbor mutations in the pre-core/core gene (pre C/C) or the preS/S gene, either of which can play a role in immune escape, viral persistence, and pathogenesis. A novel method has been developed to facilitate identification and functional analysis of full-length variant genomes of HBV, with implications for HBV diagnosis and therapy.