Evolution of cytotoxic T-lymphocyte epitopes in hepatitis B virus

Infect Genet Evol. 2007 Mar;7(2):254-62. doi: 10.1016/j.meegid.2006.10.004. Epub 2006 Nov 30.


In hepatitis B virus (HBV), while mutations that escape from cytotoxic T-lymphocyte (CTL) recognition have been described it has been difficult to determine how natural selection by host CTL has influenced long-term evolution of HBV. We used statistical analysis of published HBV genomic sequences to examine the role of natural selection in evolution of CTL epitopes. Based on a phylogenetic analysis, we identified 25 pairs of closely related genomes isolated from different HBV genotypes and examined pattern of nucleotide substitution in genomic regions encoding well-characterized CTL epitopes. On average, both epitope and non-epitope regions are subject to purifying selection acting at non-synonymous sites. However, certain CTL epitopes showed a pattern of nucleotide substitution suggesting repeated positive selection across the population. The results support the hypothesis that CTL-driven selection has been an important factor in long-term evolution of HBV.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Viral / genetics*
  • Antigens, Viral / immunology
  • Epitopes, T-Lymphocyte / genetics*
  • Evolution, Molecular*
  • Genome, Viral
  • Hepatitis B / immunology
  • Hepatitis B / virology
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology*
  • Humans
  • Phylogeny
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology


  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Viral Proteins