Global circulation patterns of seasonal influenza viruses vary with antigenic drift

Trevor Bedford¹, Steven Riley^2,3, Ian G. Barr⁴, Shobha Broor⁵, Mandeep Chadha⁶, Nancy J. Cox⁷, Rodney S. Daniels⁸, C. Palani Gunasekaran⁹, Aeron C. Hurt^4,10, Anne Kelso⁴, Alexander Klimov⁷, Nicola S. Lewis¹¹, Xiyan Li¹², John W. McCauley⁸, Takato Odagiri¹³, Varsha Potdar⁶, Andrew Rambaut^3,14,15, Yuelong Shu¹², Eugene Skepner¹¹, Derek J. Smith^11,16, Marc A. Suchard^17,18,19, Masato Tashiro¹³, Dayan Wang¹², Xiyan Xu⁷, Philippe Lemey²⁰, Colin A. Russell²¹

1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 2Department of Infectious Disease Epidemiology, Imperial College London, London, UK, 3Fogarty International Center, National Institutes of Health, Bethesda, MD, USA, 4World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, Melbourne, Australia, 5SGT Medical College, Hospital and Research Institute, Village Budhera, District Gurgaon, Haryana, India, 6National Institute of Virology, Pune, India, 7WHO Collaborating Center for Influenza, Centers for Disease Control and Prevention, Atlanta, GA, USA, 8WHO Collaborating Centre for Influenza, National Institute for Medical Research (NIMR), London, UK, 9King Institute of Preventive Medicine and Research, Guindy, Chennai, India, 10Melbourne School of Population and Global Health, University of Melbourne, Parkville VIC 3010, Australia, 11Department of Zoology, University of Cambridge, Cambridge, UK, 12WHO Collaborating Center for Influenza, China Centers for Disease Control, Beijing, China, 13WHO Collaborating Center for Influenza, National Institute for Infectious Diseases, Tokyo, Japan, 14Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK, 15>Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh, UK, 16Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands, 17Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles CA, USA, 18Department of Biomathematics David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA, 19Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA, 20Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium, 21Department of Veterinary Medicine, University of Cambridge, Cambridge, UK</sub>

Abstract

Understanding the spatio-temporal 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-characterized but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here, based on analyses of 9,604 hemagglutinin sequences of human seasonal influenza viruses from 2000-2012, 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. While genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast (E-SE) Asia, genetic variants of A/H1N1 and B viruses persisted across multiple seasons and exhibited complex global dynamics with E-SE 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 likely drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology and human behavior.

Primary analysis outline

• Sequence data compiled and subsampled
• Temporally-resolved phylogenetic trees estimated
• Circulation patterns and geographically resolved phylogenies estimated
• Multi-strain multi-deme epidemiological model simulated

Supporting data

• Antigenic phenotype for B/Victoria viruses
• Epidemic dynamics across viruses in USA and Australia
• Age structure of airline travel and influenza infections

Citation

Bedford T, Riley S, Barr IG, Broor S, Chadha M, Cox NJ, Daniels RS, Gunasekaran CP, Hurt AC, Kelso A, Klimov A, Lewis NS, Li X, McCauley JW, Odagiri T, Potdar V, Rambaut A, Shu Y, Skepner E, Smith DJ, Suchard MA, Tashiro M, Wang D, Xu X, Lemey P, Russell CA. 2015. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature 523: 217-220.