Conflicting Selection Pressures Target the NS3 Protein in Hepatitis C Virus Genotypes 1a and 1b

Virus Res. 2010 Feb;147(2):202-7. doi: 10.1016/j.virusres.2009.11.001. Epub 2009 Nov 6.

Abstract

Analysis of complete polyprotein-encoding sequences of the two most prevalent genotypes of hepatitis C virus (HCV-1a and HCV-1b) revealed evidence of abundant, slightly deleterious nonsynonymous variants subject to ongoing purifying selection. In the case of both HCV-1a and HCV-1b, the NS3 protein demonstrated a high incidence of forward-and-backward or parallel nonsynonymous changes in CTL epitopes as measured by the phylogenetic consistency index. These results imply that certain nonsynonymous mutations have occurred frequently throughout the HCV-1a and HCV-1b phylogenies in the codons encoding the epitopes in NS3. This pattern is best explained by the frequent re-occurrence of the same set of escape mutations in CTL epitopes of NS3, which are selectively favored within hosts presenting the class I major histocompatability complex molecule, but subject to purifying selection in the population at large. This pattern was more pronounced in HCV-1b than in HCV-1a, suggesting that there may be differences between the two genotypes with respect to NS3's interaction with host immune recognition.

Publication types

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

MeSH terms

  • Adaptation, Biological*
  • Amino Acid Substitution / genetics
  • Epitopes, T-Lymphocyte / genetics
  • Evolution, Molecular
  • Genotype
  • Hepacivirus / genetics*
  • Hepacivirus / immunology*
  • Humans
  • Mutation, Missense
  • Selection, Genetic*
  • Sequence Analysis, DNA
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins