Trevor Bedford1, Marc A. Suchard2,3,4, Philippe Lemey5, Gytis Dudas1, Victoria Gregory6, Alan J. Hay6, John W. McCauley6, Colin A. Russell7,8, Derek J. Smith7,8,9, Andrew Rambaut1,10
1Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK, 2Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles CA, USA, 3Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles CA, USA, 4Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles CA, USA, 5Department of Microbiology and Immunology, Katholieke Universiteit Leuven, Leuven, Belgium, 6Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, UK, 7Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, UK, 8WHO Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge, UK, 9Department of Virology, Erasmus Medical Centre, Rotterdam, Netherlands, 10Fogarty International Center, National Institutes of Health, Bethesda, MD, USA
Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza A subtypes H3N2 and H1N1 and influenza B lineages Victoria and Yamagata, we determine patterns of antigenic drift across lineages and show that antigenic drift drives incidence rates and mediates interference between influenza lineages. Additionally, we describe the selective underpinnings of differences in antigenic drift across lineages. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution.
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