The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes

Immunity. 2001 Dec;15(6):883-95. doi: 10.1016/s1074-7613(01)00245-x.

Abstract

CD8(+) cytotoxic T lymphocytes (CTL) are thought to control hepatitis C virus (HCV) replication and so we investigated why this response fails in persistently infected individuals. The HCV quasispecies in three persistently infected chimpanzees acquired mutations in multiple epitopes that impaired class I MHC binding and/or CTL recognition. Most escape mutations appeared during acute infection and remained fixed in the quasispecies for years without further diversification. A statistically significant increase in the amino acid replacement rate was observed in epitopes versus adjacent regions of HCV proteins. In contrast, most epitopes were intact when hepatitis C resolved spontaneously. We conclude that CTL exert positive selection pressure against the HCV quasispecies and the outcome of infection is predicted by mutations in class I MHC restricted epitopes.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Amino Acid Sequence
  • Animals
  • Antigenic Variation / genetics*
  • Cell Line / immunology
  • Epitopes / genetics*
  • Epitopes / immunology
  • Follow-Up Studies
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C / immunology*
  • Hepatitis C / virology
  • Hepatitis C Antigens / genetics*
  • Hepatitis C Antigens / immunology
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Histocompatibility Antigens Class I / immunology
  • Molecular Sequence Data
  • Mutation*
  • Pan troglodytes
  • RNA, Viral / genetics
  • Remission, Spontaneous
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / immunology
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / immunology

Substances

  • Epitopes
  • Hepatitis C Antigens
  • Histocompatibility Antigens Class I
  • NS2 protein, Hepatitis C virus
  • NS3 protein, hepatitis C virus
  • NS4 protein, hepatitis C virus
  • RNA, Viral
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • glycoprotein E2, Hepatitis C virus
  • NS-5 protein, hepatitis C virus