Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants

J Gen Virol. 1996 Jun;77 ( Pt 6):1129-38. doi: 10.1099/0022-1317-77-6-1129.

Abstract

We have analysed serum samples taken from hepatitis B virus (HBV) e antigen (HBeAg)-positive and HBeAg-negative chronic active hepatitis (CAH) patients by PCR using primers spanning the pre-core/core (C) and pre-S1/S2 ORFs. Nucleotide sequence analysis showed that among 18 HBV-infected CAH patients, 11 had virus with a G to A mutation (nucleotide 1896; leading to the formation of a stop codon) and one patient also had virus with an additional G to A mutation three nucleotides downstream (nucleotide 1899). HBV from three patients that were HBeAg-negative showed a 1 bp deletion at nucleotide 1937, causing pre-termination of the C gene. Mutation frequencies in the sequences identified as coding for cytotoxic T lymphocyte epitopes, B cell epitopes, CD4+ helper T cell epitopes and arginine-rich regions of the HBV C peptide were investigated. Mutations were more frequently identified in these regions, suggesting that the mutations might have been selected as a result of immune responses.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Chronic Disease
  • Codon
  • DNA Primers
  • DNA, Viral / blood*
  • DNA, Viral / isolation & purification
  • Female
  • Genes, Viral*
  • Genome, Viral
  • Hepatitis B / pathology
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Open Reading Frames
  • Point Mutation*
  • Polymerase Chain Reaction / methods
  • Sequence Deletion*
  • Viral Core Proteins / biosynthesis*

Substances

  • Codon
  • DNA Primers
  • DNA, Viral
  • Viral Core Proteins