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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Archives of Virology (2018)