Molecular epidemiology and immunology of hepatitis B virus infection - an update

Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. This review provides an update on the molecular epidemiology and immunology of HBV infection. DNA sequencing has allowed replacement of the initial serotypic classification of HBV strains by a more systematic genotype system that currently consists of 7 members (genotypes A-G). More recently, sequence analysis of virus isolates from many individual patients has revealed the occurrence of certain mutational hot spots in the genome, some of which appear to correlate with the patient's immunological and/or disease status; however, cause and effect are not always easily discernible. This holds particularly for the issue of whether virus variants exist that have, per se, an increased pathogenic potential; due to the scarcity of appropriate experimental in vivo models, such hypotheses are difficult to prove. Similarly, because of the compact organization of the HBV genome, almost every single mutation may have pleiotropic phenotypic effects. Nonetheless, there is accumulating evidence that at least some frequently observed mutations are causally related to viral escape from selective pressures, such as the presence of antibodies against dominant B cell epitopes, or drugs that inhibit the viral reverse transcriptase; possibly, this is also true for the cellular immune response. Therefore, despite the availability of an effective prophylactic vaccine, further extensive efforts are required to monitor the emergence of vaccination- and therapy-resistant HBV variants and to prevent their spread in the general population.