Letter | Published:

A synchronized global sweep of the internal genes of modern avian influenza virus

Nature volume 508, pages 254257 (10 April 2014) | Download Citation

Abstract

Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health1. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood2,3. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts3,4,5,6,7,8. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including ‘relaxed’ molecular clock models9, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds—as well as those from humans, swine and the equine H3N8 lineage—sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.

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Accessions

Data deposits

Sequences for A/equine/Detroit/3/1964(H7N7), A/chicken/Japan/1925(H7N7) and A/duck/Manitoba/1953(H10N7) have been deposited in the GenBank database under accession numbers KF435047KF435062 and KF619244KF619250.

References

  1. 1.

    , & The challenge of emerging and re-emerging infectious diseases. Nature 430, 242–249 (2004)

  2. 2.

    et al. Cross-species virus transmission and the emergence of new epidemic diseases. Microbiol. Mol. Biol. Rev. 72, 457–470 (2008)

  3. 3.

    The Evolution and Emergence of RNA Viruses (Oxford Univ. Press, 2009)

  4. 4.

    , , , & Evolution and ecology of influenza A viruses. Microbiol. Rev. 56, 152–179 (1992)

  5. 5.

    , , & Long term trends in the evolution of H(3) HA1 human influenza type A. Proc. Natl Acad. Sci. USA 94, 7712–7718 (1997)

  6. 6.

    et al. The genomic and epidemiological dynamics of human influenza A virus. Nature 453, 615–619 (2008)

  7. 7.

    et al. The evolutionary genetics and emergence of avian influenza viruses in wild birds. PLoS Pathog. 4, e1000076 (2008)

  8. 8.

    & Hitchhiking and the population genetic structure of avian influenza virus. J. Mol. Evol. 70, 98–105 (2010)

  9. 9.

    , , & Relaxed phylogenetics and dating with confidence. PLoS Biol. 4, e88 (2006)

  10. 10.

    , , & Isolation of a virus causing respiratory disease in horses. Acta Virol. 2, 52–61 (1958)

  11. 11.

    & Historical thoughts on influenza viral ecosystems, or behold a pale horse, dead dogs, failing fowl, and sick swine. Influenza Other Respir. Viruses 4, 327–337 (2010)

  12. 12.

    History and course of the epizoötic among horses upon the North American continent in 1872–73. Publ. Health Pap. Rep. 1, 88–109 (1873)

  13. 13.

    & An avian outbreak associated with panzootic equine influenza in 1872: an early example of highly pathogenic avian influenza? Influenza Other Respir. Viruses 4, 373–377 (2010)

  14. 14.

    , & Comparison of avian and human influenza A viruses reveals a mutational bias on the viral genomes. J. Virol. 80, 11887–11891 (2006)

  15. 15.

    Epizoozia tifoide nei gallinacei. Annli Reale Accad. Agric. Torino 21, 87–126 (1878)

  16. 16.

    & in Avian Influenza (ed. ) 145–189 (Blackwell, 2008)

  17. 17.

    et al. Dating the emergence of pandemic influenza viruses. Proc. Natl Acad. Sci. USA 106, 11709–11712 (2009)

  18. 18.

    & epizootic of equine influenza, 1963: Epizootiology. Public Health Rep. 79, 393–398 (1964)

  19. 19.

    , , & The B allele of the NS gene of avian influenza viruses, but not the A allele, attenuates a human influenza A virus for squirrel monkeys. Virology 171, 1–9 (1989)

  20. 20.

    Genetic hitchhiking. Phil. Trans. R. Soc. Lond. B 355, 1553–1562 (2000)

  21. 21.

    et al. A distinct lineage of influenza A virus from bats. Proc. Natl Acad. Sci. USA 109, 4269–4274 (2012)

  22. 22.

    et al. New World bats harbor diverse influenza A viruses. PLoS Pathog. 9, e1003657 (2013)

  23. 23.

    , , & Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969–1973 (2012)

  24. 24.

    , & Estimation of branching dates among primates by molecular clocks of nuclear DNA which slowed down in Hominoidea. J. Hum. Evol. 18, 461–476 (1989)

  25. 25.

    & Estimating divergence dates from molecular sequences. Mol. Biol. Evol. 15, 442–448 (1998)

  26. 26.

    & Estimation of primate speciation dates using local molecular clocks. Mol. Biol. Evol. 17, 1081–1090 (2000)

  27. 27.

    & Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees. Comput. Appl. Biosci. 13L, 235–238 (1997)

  28. 28.

    Some probabilistic and statistical problems in the analysis of DNA sequences. Lect. Math Life Sci. 17, 57–86 (1986)

  29. 29.

    Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites. Mol. Biol. Evol. 10, 1396–1401 (1993)

  30. 30.

    , & Smooth skyride through a rough skyline: Bayesian coalescent-based inference of population dynamics. Mol. Biol. Evol. 25, 1459–1471 (2008)

  31. 31.

    et al. The influenza virus resource at the National Center for Biotechnology Information. J. Virol. 82, 596–601 (2008)

  32. 32.

    et al. Avian influenza H5N1 in tigers and leopards. Emerg. Infect. Dis. 10, 2189–2191 (2004)

  33. 33.

    MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792–1797 (2004)

  34. 34.

    et al. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731–2739 (2011)

  35. 35.

    & Homologous recombination in negative sense RNA viruses. Viruses 3, 1358–1373 (2011)

  36. 36.

    et al. RDP3: a flexible and fast computer program for analyzing recombination. Bioinformatics 26, 2462–2463 (2010)

  37. 37.

    et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 459, 1122–1126 (2009)

  38. 38.

    et al. Transmission of equine influenza virus to dogs. Science 310, 482–485 (2005)

  39. 39.

    , & Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature 274, 334–339 (1978)

  40. 40.

    , & Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences. Mol. Biol. Evol. 23, 7–9 (2006)

  41. 41.

    PAUP*. Phylogenetic Analysis Using Parsimony (*and Other Methods). Version 4 (Sinauer Associates, 2003)

  42. 42.

    et al. A random effects branch-site model for detecting episodic diversifying selection. Mol. Biol. Evol. 28, 3033–3043 (2011)

  43. 43.

    et al. Evidence for the circulation and inter-hemispheric movement of the H14 subtype influenza A virus. PLoS ONE 8, e59216 (2013)

  44. 44.

    et al. Single-reaction genomic amplification accelerates sequencing and vaccine production for classical and Swine origin human influenza a viruses. J. Virol. 83, 10309–10313 (2009)

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Acknowledgements

We thank J. Barnes, S. Meno, M. Shaw, R. Donis, S. Krauss, K. Friedman, R. Webster, Y. Muramoto and Y. Kawaoka for assistance in locating and sequencing A/equine/Detroit/3/1964(H7N7), A/chicken/Japan/1925(H7N7) and A/duck/Manitoba/1953(H10N7); M. Sanderson for comments on the HSLC model; S. Zohari for discussions of the NS1/2 A and B lineages; and M. Nachman, Y. Kawaoka, T. Watts, J. Cox, and D. Gill for comments. This work was supported by grants from the David and Lucile Packard Foundation to M.W., and the Wellcome Trust (grant no. 092807) to A.R. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 278433-PREDEMICS and European Research Council grant agreement no. 260864. The methodological approach was developed in part with support from a grant from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. (R01AI084691).

Author information

Affiliations

  1. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona 85721, USA

    • Michael Worobey
    •  & Guan-Zhu Han
  2. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK

    • Andrew Rambaut
  3. Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA

    • Andrew Rambaut

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Contributions

M.W., G.-Z.H. and A.R. designed the study. M.W. and A.R. conceived the analytical approach, and A.R. developed the software. G.-Z.H., M.W. and A.R. prepared the data sets. M.W., G.-Z.H. and A.R. performed the phylogenetic analyses. M.W. conducted the U content analyses. M.W. and A.R. wrote the paper. All authors discussed all the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Michael Worobey or Andrew Rambaut.

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    Supplementary Information

    This file contains a Supplementary Discussion, Supplementary Figure 1 and Supplementary References.

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https://doi.org/10.1038/nature13016

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