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Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides

Author

Listed:
  • Sophie A. Valkenburg

    (University of Melbourne)

  • Sergio Quiñones-Parra

    (University of Melbourne)

  • Stephanie Gras

    (School of Biomedical Sciences, Monash University)

  • Naomi Komadina

    (WHO Collaborating Centre for Reference and Research on Influenza
    Melbourne School of Population and Global Health, the University of Melbourne
    School of Public Health and Preventive Medicine, Monash University)

  • Jodie McVernon

    (Melbourne School of Population and Global Health, the University of Melbourne)

  • Zhongfang Wang

    (University of Melbourne)

  • Hanim Halim

    (School of Biomedical Sciences, Monash University)

  • Pina Iannello

    (WHO Collaborating Centre for Reference and Research on Influenza)

  • Catherine Cole

    (School of Paediatrics and Child Health, University of Western)

  • Karen Laurie

    (WHO Collaborating Centre for Reference and Research on Influenza)

  • Anne Kelso

    (WHO Collaborating Centre for Reference and Research on Influenza)

  • Jamie Rossjohn

    (School of Biomedical Sciences, Monash University
    Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park)

  • Peter C. Doherty

    (University of Melbourne
    St Jude Children’s Research Hospital)

  • Stephen J. Turner

    (University of Melbourne)

  • Katherine Kedzierska

    (University of Melbourne)

Abstract

Influenza A virus-specific CD8+ cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8+ T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide–MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.

Suggested Citation

  • Sophie A. Valkenburg & Sergio Quiñones-Parra & Stephanie Gras & Naomi Komadina & Jodie McVernon & Zhongfang Wang & Hanim Halim & Pina Iannello & Catherine Cole & Karen Laurie & Anne Kelso & Jamie Ross, 2013. "Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3663
    DOI: 10.1038/ncomms3663
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