The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound

Abstract

The hepatitis B virus (HBV) mutation that encodes rtA181T is selected in the viral polymerase during antiviral drug therapy and can also encode a stop codon in the overlapping surface gene at amino acid 172 (sW172*) resulting in truncation of the last 55 amino acids of the C-terminal hydrophobic region of the surface proteins. This mutation is usually detected as a mixed population with wild-type HBV. In vitro analysis revealed that the rtA181T/sW172* variant is not only defective in secretion of viral particles causing intracellular retention of surface proteins, it also has a dominant negative effect on virion but not subviral particle secretion when coexpressed with the wild type. This do..