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Characterization of the 1918 influenza virus polymerase genes

Naturevolume 437pages889893 (2005) | Download Citation



The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors1, thereby having a role in host specificity2,3. The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian sequences, the nucleotide sequences of the 1918 polymerase genes have more synonymous differences than expected, suggesting evolutionary distance from known avian strains. Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus4,5,6,7,8, and propose that the 1918 virus was not a reassortant virus (like those of the 1957 and 1968 pandemics9,10), but more likely an entirely avian-like virus that adapted to humans. These data support prior phylogenetic studies suggesting that the 1918 virus was derived from an avian source11. A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.

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The research described in this report was done using stringent safety precautions to protect the laboratory workers, the environment and the public from this virus. The intention of this research is to provide the basis for understanding how influenza pandemic strains form and to help ascertain the risk of future influenza pandemics. This study was partially supported by a grant to J.K.T. from the National Institutes of Health, and by intramural funds from the Armed Forces Institute of Pathology. The opinions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the US Department of Defense.Author Contributions J.K.T. planned the project, and A.H.R., R.M.L., R.W. and G.J. generated the sequence data. J.K.T., A.H.R. and T.G.F. performed data analysis. J.K.T. wrote the manuscript.

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Author notes

    • Ann H. Reid

    Present address: Board on Life Sciences, The National Academies, 6th Floor, 500 Fifth Street N.W., Washington, DC, 20001, USA

    • Raina M. Lourens

    Present address: University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 200 CMAB, Iowa City, Iowa, 52242, USA


  1. Department of Molecular Pathology, Armed Forces Institute of Pathology, Maryland, 20850, Rockville, USA

    • Jeffery K. Taubenberger
    • , Ann H. Reid
    • , Raina M. Lourens
    • , Ruixue Wang
    • , Guozhong Jin
    •  & Thomas G. Fanning


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Competing interests

Coding sequences of the PB2, PB1 and PA genes have been deposited in GenBank under accession numbers DQ208309, DQ208310 and DQ208311, respectively. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Jeffery K. Taubenberger.

Supplementary information

  1. Supplementary Table

    Influenza sequences used in the analysis (DOC 454 kb)

  2. Supplementary Figure 1

    Complete coding sequence of the 1918 influenza virus PB2 gene segment (DOC 67 kb)

  3. Supplementary Figure 2

    Theoretical translation of the 1918 influenza virus PB1 open reading frame (a) and the PB1-F2 open reading frame (b) as aligned to representative PB1 proteins from other human and animal influenza A viruses. (PPT 46 kb)

  4. Supplementary Figure Legends

    Text to accompany the above Supplementary Figures. (DOC 23 kb)

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