Viral escape by selection of cytotoxic T cell-resistant variants in influenza a virus pneumonia

Graeme E. Price, Rong Ou, Hong Jiang, Lei Huang, Demetrius Moskophidis

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Antigenic variation is a strategy exploited by influenza viruses to promote survival in the face of the host adaptive immune response and constitutes a major obstacle to efficient vaccine development. Thus, variation in the surface glycoproteins hemagglutinin and neuraminidase is reflected by changes in susceptibility to antibody neutralization. This has led to the current view that antibody-mediated selection of influenza A viruses constitutes the basis for annual influenza epidemics and periodic pandemics. However, infection with this virus: elicits a vigorous protective CD8+ cytotoxic T lymphocyte (CTL) response, suggesting that CD8+ CTLs might exert selection pressure on the virus. Studies with influenza A virus- infected transgenic mice bearing a T cell receptor (TCR) specific for viral nucleoprotein reveal that virus reemergence and persistence occurs weeks after the acute infection has apparently been controlled. The persisting virus is no longer recognized by CTLs, indicating that amino acid changes in the major viral nucleoprotein CTL epitope can be rapidly accumulated in vivo. These mutations lead to a total or partial loss of recognition by polyclonal CTLs by affecting presentation of vital peptide by class I major histocompatibility complex (MHC) molecules, or by interfering with TC recognition of the mutant peptide-MIHC complex. These data illustrate the distinct features of pulmonary immunity in selection of CTL escape variants. The likelihood of emergence and the biological impact of CTL escape variants on the clinical outcome of influenza pneumonia in an immunocompetent host, which is relevant for the design of preventive vaccines against this and other respiratory vital infections, are discussed.

Original languageEnglish (US)
Pages (from-to)1853-1867
Number of pages15
JournalJournal of Experimental Medicine
Volume191
Issue number11
DOIs
StatePublished - Jun 5 2000

Keywords

  • CD8 CTL escape variants
  • Influenza A virus
  • Influenza viral pneumonia
  • T cell receptor transgenic mice
  • Viral persistence

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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