Molecular genesis of drug-resistant and vaccine-escape HBV mutants

Abstract

A high rate of viral turnover, combined with an error-prone polymerase, results in a very high frequency of mutational events during HBV replication. Not surprisingly, particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antivirals), readily select out new 'escape' mutants. The introduction of nucleoside/nucleotide analogue (NA) therapy for chronic hepatitis B has witnessed the emergence of antiviral drug resistance as the major factor limiting drug efficacy. Furthermore, because of the overlap of the viral polymerase and envelope reading frames in the HBV DNA genome, NA resistance-associated mutations selected in the catalytic domains of the po..