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Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses

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  • Peter R. Wilker

    (University of Wisconsin School of Veterinary Medicine
    Present address: Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, Wisconsin 54601, USA)

  • Jorge M. Dinis

    (University of Wisconsin School of Veterinary Medicine)

  • Gabriel Starrett

    (University of Wisconsin School of Medicine and Public Health)

  • Masaki Imai

    (University of Wisconsin School of Veterinary Medicine)

  • Masato Hatta

    (University of Wisconsin School of Veterinary Medicine)

  • Chase W. Nelson

    (University of South Carolina)

  • David H. O’Connor

    (University of Wisconsin School of Medicine and Public Health
    Wisconsin National Primate Research Center)

  • Austin L. Hughes

    (University of South Carolina)

  • Gabriele Neumann

    (University of Wisconsin School of Veterinary Medicine)

  • Yoshihiro Kawaoka

    (University of Wisconsin School of Veterinary Medicine
    Institute of Medical Science, University of Tokyo
    International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo
    ERATO Infection-Induced Host Responses Project)

  • Thomas C. Friedrich

    (University of Wisconsin School of Veterinary Medicine
    Wisconsin National Primate Research Center)

Abstract

The emergence of human-transmissible H5N1 avian influenza viruses poses a major pandemic threat. H5N1 viruses are thought to be highly genetically diverse both among and within hosts; however, the effects of this diversity on viral replication and transmission are poorly understood. Here we use deep sequencing to investigate the impact of within-host viral variation on adaptation and transmission of H5N1 viruses in ferrets. We show that, although within-host genetic diversity in haemagglutinin (HA) increases during replication in inoculated ferrets, HA diversity is dramatically reduced upon respiratory droplet transmission, in which infection is established by only 1–2 distinct HA segments from a diverse source virus population in transmitting animals. Moreover, minor HA variants present in as little as 5.9% of viruses within the source animal become dominant in ferrets infected via respiratory droplets. These findings demonstrate that selective pressures acting during influenza virus transmission among mammals impose a significant bottleneck.

Suggested Citation

  • Peter R. Wilker & Jorge M. Dinis & Gabriel Starrett & Masaki Imai & Masato Hatta & Chase W. Nelson & David H. O’Connor & Austin L. Hughes & Gabriele Neumann & Yoshihiro Kawaoka & Thomas C. Friedrich, 2013. "Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3636
    DOI: 10.1038/ncomms3636
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