Letter

Global circulation patterns of seasonal influenza viruses vary with antigenic drift

  • Nature volume 523, pages 217220 (09 July 2015)
  • doi:10.1038/nature14460
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Abstract

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized1,2,3,4,5,6,7, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.

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Acknowledgements

We thank National Influenza Centres worldwide for their contributions to influenza virus surveillance. T.B. was supported by a Newton International Fellowship from the Royal Society and through National Institutes of Health (NIH) U54 GM111274. S.R. was supported by Medical Research Council (UK, Project MR/J008761/1), Wellcome Trust (UK, Project 093488/Z/10/Z), Fogarty International Centre (USA, R01 TW008246-01), Department of Homeland Security (USA, RAPIDD program), National Institute of General Medical Sciences (USA, MIDAS U01 GM110721-01) and National Institute for Health Research (UK, Health Protection Research Unit funding). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza was supported by the Australian Government Department of Health and thanks N. Komadina and Y.-M. Deng. The Atlanta WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza was supported by the US Department of Health and Human Services. NIV thanks A.C. Mishra, M. Chawla-Sarkar, A. M. Abraham, D. Biswas, S. Shrikhande, B. AnuKumar, and A. Jain. Influenza surveillance in India was expanded, in part, through US Cooperative Agreements (5U50C1024407 and U51IP000333) and by the Indian Council of Medical Research. M.A.S. was supported through National Science Foundation DMS 1264153 and NIH R01 AI 107034. Work of the WHO Collaborating Centre for Reference and Research on Influenza at the MRC National Institute for Medical Research was supported by U117512723. P.L., A.R. & M.A.S were supported by EU Seventh Framework Programme [FP7/2007-2013] under Grant Agreement no. 278433-PREDEMICS and ERC Grant agreement no. 260864. C.A.R. was supported by a University Research Fellowship from the Royal Society.

Author information

Author notes

    • Alexander Klimov

    Deceased.

Affiliations

  1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

    • Trevor Bedford
  2. MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London SW7 2AZ, UK

    • Steven Riley
  3. Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA

    • Steven Riley
    •  & Andrew Rambaut
  4. World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria 3000, Australia

    • Ian G. Barr
    • , Aeron C. Hurt
    •  & Anne Kelso
  5. SGT Medical College, Hospital and Research Institute, Village Budhera, District Gurgaon, Haryana 122505, India

    • Shobha Broor
  6. National Institute of Virology, Pune 411001, India

    • Mandeep Chadha
    •  & Varsha Potdar
  7. WHO Collaborating Center for Reference and Research on Influenza, Centers for Disease Control and Prevention, Atlanta, Georgia 30329, USA

    • Nancy J. Cox
    • , Alexander Klimov
    •  & Xiyan Xu
  8. WHO Collaborating Center for Reference and Research on Influenza, Medical Research Council National Institute for Medical Research (NIMR), London NW7 1AA, UK

    • Rodney S. Daniels
    •  & John W. McCauley
  9. King Institute of Preventive Medicine and Research, Guindy, Chennai 600032, India

    • C. Palani Gunasekaran
  10. Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria 3010, Australia

    • Aeron C. Hurt
  11. Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK

    • Nicola S. Lewis
    • , Eugene Skepner
    •  & Derek J. Smith
  12. WHO Collaborating Center for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China

    • Xiyan Li
    • , Yuelong Shu
    •  & Dayan Wang
  13. WHO Collaborating Center for Reference and Research on Influenza, National Institute of Infectious Diseases, Tokyo 208-0011, Japan

    • Takato Odagiri
    •  & Masato Tashiro
  14. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK

    • Andrew Rambaut
  15. Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK

    • Andrew Rambaut
  16. Department of Viroscience, Erasmus Medical Center, 3015 Rotterdam, The Netherlands

    • Derek J. Smith
  17. Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, California 90095, USA

    • Marc A. Suchard
  18. Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095, USA

    • Marc A. Suchard
  19. Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095, USA

    • Marc A. Suchard
  20. Department of Microbiology and Immunology, Rega Institute, KU Leuven – University of Leuven, 3000 Leuven, Belgium

    • Philippe Lemey
  21. Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK

    • Colin A. Russell

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Contributions

C.A.R. and T.B. conceived the research. C.A.R. and T.B. drafted the manuscript with substantial support from P.L. and S.R. I.G.B., S.B., M.C., N.J.C., R.S.D., C.P.G., A.C.H., A.K., A.Kl. X.L., J.W.M., T.O., V.P., Y.S., M.T., D.W. and X.X. coordinated and produced the influenza surveillance data. T.B. performed the modeling and data analyses along with C.A.R., S.R., P.L., M.A.S. and A.R. T.B. created the figures. All authors discussed the results and contributed to the revision of the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Colin A. Russell.

Extended data

Extended data figures

  1. 1.

    Spatial distribution of 4,006 H3N2, 2,144 H1N1, 1,999 Vic and 1,455 Yam samples.

  2. 2.

    Inferred location of the trunk of H3N2 tree through time in the primary data set (a) and in a smaller secondary data set (b).

  3. 3.

    Average inferred geographic history of region-specific samples for H3N2, former seasonal H1N1, Vic and Yam viruses from 2000 to 2012.

  4. 4.

    Maximum clade credibility (MCC) trees for region-specific samples from USA/Canada, India and South China for H3N2, H1N1, Vic and Yam viruses.

  5. 5.

    Antigenic map of Vic viruses primarily collected in 2008 (a), age distribution of infections for H3N2 (b), H1N1 (c) and B (d) in Australia 2000–2011, age distribution of 102.5 million passengers at London Heathrow and London Gatwick airports during 2011 (e), time series of virological characterizations from 2000 to 2012 of viruses from the USA by US CDC and from Australia by VIDRL for H3N2 (f), H1N1 (g), Vic (h) and Yam (i).

  6. 6.

    Combined persistence estimates across pairs of regions for H3N2, H1N1, Vic and Yam (a) and Spearman correlation of a region’s persistence vs the region’s contribution to phylogenetic ancestry for H3N2, H1N1, Vic and Yam (b).

  7. 7.

    Simulation results for a model parameterized for slow antigenic drift (a), moderate antigenic drift (b), and fast antigenic drift (c).

  8. 8.

    Simulation results showing relationship between antigenic drift and persistence as a function of seasonality (a) and simulation results showing the effects of modulating transmission rate β on model behaviour (b).

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains a Supplementary Discussion and additional references.

Excel files

  1. 1.

    Supplementary Data

    This file contains the genetic sequence accession numbers.

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