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Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts

Author

Listed:
  • Shufang Fan

    (Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison)

  • Masato Hatta

    (Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison)

  • Jin Hyun Kim

    (Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison
    Present address: Department of Pharmaceutical Science, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109, USA)

  • Peter Halfmann

    (Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison)

  • Masaki Imai

    (Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison)

  • Catherine A. Macken

    (Los Alamos National Laboratory)

  • Mai Quynh Le

    (National Institute of Hygiene and Epidemiology)

  • Tung Nguyen

    (National Centre for Veterinary Diagnostics)

  • Gabriele Neumann

    (Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison)

  • Yoshihiro Kawaoka

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

Abstract

Highly pathogenic avian H5N1 influenza viruses have sporadically transmitted to humans causing high mortality. The mechanistic basis for adaptation is still poorly understood, although several residues in viral protein PB2 are known to be important for this event. Here, we demonstrate that three residues, 147T, 339T and 588T, in PB2 play critical roles in the virulence of avian H5N1 influenza viruses in a mammalian host in vitro and in vivo and, together, result in a phenotype comparable to that conferred by the previously known PB2-627K mutation with respect to virus polymerase activity. A virus with the three residues and 627K in PB2, as has been isolated from a lethal human case, is more pathogenic than viruses with only the three residues or 627K in PB2. Importantly, H5N1 viruses bearing the former three PB2 residues have circulated widely in recent years in avian species in nature.

Suggested Citation

  • Shufang Fan & Masato Hatta & Jin Hyun Kim & Peter Halfmann & Masaki Imai & Catherine A. Macken & Mai Quynh Le & Tung Nguyen & Gabriele Neumann & Yoshihiro Kawaoka, 2014. "Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6021
    DOI: 10.1038/ncomms6021
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