Molecular Epidemiology and Immunology of Hepatitis B Virus Infection – An Update

Abstract

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.

Hepatitis B virus mutations associated with fulminant hepatitis induce apoptosis in primaryTupaiahepatocytes

“…1,2 Viral factors such as HBV genotypes, 3 as well as the host immune response, have been implicated in the pathogenesis and clinical outcome of HBV infection. 2 Furthermore, evidence has been accumulating that certain HBV mutants lead to particular clinical manifestations, influence the natural course of infection, and modulate the response to antiviral treatment. 1,[4][5][6][7] Several independent studies have identified distinct mutations clustered in enhancer II of the HBV core promoter in association with fulminant [8][9][10][11][12] and chronic severe hepatitis B.…”

Hepatitis B Virus Genotypes in Latvia

“…HBc CTL epitope 18-27 mutations Ser21Asn/Ala/Val were found earlier in HLA-A2-positive CH patients [30]. In other HBc CTL epitopes: 63-71 and 141-149 [31], the following substitutions were found Gly63Val (twice in AH and CH patients), Glu64Asp (twice in LC and CH patients), and Glu64Val (once in AH patient). The Glu64Asp substitution was combined with two other mutations within the same epitope: Leu65Val and Ala69Gly.…”

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

“…This figure is one to two orders of magnitude lower than in other viruses lacking polymerase-associated proof-reading functions, such as RNA viruses [17], and four orders of magnitude greater than in "common" (without reverse transcriptase) DNA viruses [18]. Therefore, HBV populations may evolve at a faster rate than most DNA viruses as a result of environmental factors; hence, viral HBV mutants may likely emerge in response to those factors.…”