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Research Article

Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene

Ann H. Reid, Thomas G. Fanning, Johan V. Hultin, and Jeffery K. Taubenberger
PNAS February 16, 1999 96 (4) 1651-1656; https://doi.org/10.1073/pnas.96.4.1651
Ann H. Reid
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Thomas G. Fanning
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Johan V. Hultin
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Jeffery K. Taubenberger
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  1. Communicated by Edwin D. Kilbourne, New York Medical College, Valhalla, NY (received for review August 7, 1998)

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Abstract

The “Spanish” influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in 1918. Influenza RNA was also isolated from lung tissue samples from two additional victims of the lethal 1918 influenza: one formalin-fixed, paraffin-embedded sample and one frozen sample obtained by in situ biopsy of the lung of a victim buried in permafrost since 1918. The complete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/New York/1/18 and A/Brevig Mission/1/18). The sequences show little variation. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918.

Footnotes

    • ↵* To whom reprint requests should be addressed. e-mail: reid{at}afip.osd.mil.

    • Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF117241 for A/South Carolina/1/18, AF116576 for A/New York/1/18, and AF116575 for A/Brevig Mission/1/18).

    • A Commentary on this article begins on page 1164.

  • ABBREVIATIONS

    HA,
    hemagglutinin;
    NJ,
    neighbor-joining;
    RT-PCR,
    reverse transcription–PCR
    • Received August 7, 1998.
    • Accepted November 18, 1998.
    • Copyright © 1999, The National Academy of Sciences
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    Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene
    Ann H. Reid, Thomas G. Fanning, Johan V. Hultin, Jeffery K. Taubenberger
    Proceedings of the National Academy of Sciences Feb 1999, 96 (4) 1651-1656; DOI: 10.1073/pnas.96.4.1651

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    Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene
    Ann H. Reid, Thomas G. Fanning, Johan V. Hultin, Jeffery K. Taubenberger
    Proceedings of the National Academy of Sciences Feb 1999, 96 (4) 1651-1656; DOI: 10.1073/pnas.96.4.1651
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    Proceedings of the National Academy of Sciences: 96 (4)
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