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Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

Author

Listed:
  • Darwyn Kobasa

    (University of Wisconsin
    Canadian Science Centre for Human and Animal Health)

  • Ayato Takada

    (Institute of Medical Science, University of Tokyo
    Japan Science and Technology Agency)

  • Kyoko Shinya

    (Institute of Medical Science, University of Tokyo
    Tohoku University Graduate School of Medicine)

  • Masato Hatta

    (University of Wisconsin)

  • Peter Halfmann

    (University of Wisconsin)

  • Steven Theriault

    (University of Manitoba)

  • Hiroshi Suzuki

    (Niigata University)

  • Hidekazu Nishimura

    (Sendai National Hospital)

  • Keiko Mitamura

    (Nippon Kokan Hospital
    Kawasaki Municipal Hospital)

  • Norio Sugaya

    (Nippon Kokan Hospital
    Keiyu Hospital)

  • Taichi Usui

    (Shizuoka University)

  • Takeomi Murata

    (Shizuoka University)

  • Yasuko Maeda

    (Institute of Medical Science, University of Tokyo)

  • Shinji Watanabe

    (University of Wisconsin)

  • M. Suresh

    (University of Wisconsin)

  • Takashi Suzuki

    (Japan Science and Technology Agency
    University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century)

  • Yasuo Suzuki

    (Japan Science and Technology Agency
    University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century)

  • Heinz Feldmann

    (University of Manitoba)

  • Yoshihiro Kawaoka

    (University of Wisconsin
    Institute of Medical Science, University of Tokyo
    Japan Science and Technology Agency)

Abstract

The ‘Spanish’ influenza pandemic of 1918–19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people1 died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin2 (HA) and neuraminidase3 (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal4,5. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic6.

Suggested Citation

  • Darwyn Kobasa & Ayato Takada & Kyoko Shinya & Masato Hatta & Peter Halfmann & Steven Theriault & Hiroshi Suzuki & Hidekazu Nishimura & Keiko Mitamura & Norio Sugaya & Taichi Usui & Takeomi Murata & Ya, 2004. "Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus," Nature, Nature, vol. 431(7009), pages 703-707, October.
    • Handle: RePEc:nat:nature:v:431:y:2004:i:7009:d:10.1038_nature02951
    DOI: 10.1038/nature02951
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    Cited by:

    1. Noymer, Andrew, 2009. "Testing the influenza-tuberculosis selective mortality hypothesis with Union Army data," Social Science & Medicine, Elsevier, vol. 68(9), pages 1599-1608, May.
    2. Amanda Guimbeau & Nidhiya Menon & Aldo Musacchio, 2020. "The Brazilian Bombshell? The Long-Term Impact of the 1918 Influenza Pandemic the South American Way," NBER Working Papers 26929, National Bureau of Economic Research, Inc.

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