Integrating influenza antigenic dynamics with molecular evolution.
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 lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. 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. DOI: http://dx.doi.org/10.7554/eLife.01914.001.
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
Trevor
T
Bedford
Marc A
MA
Suchard
Philippe
P
Lemey
Gytis
G
Dudas
Victoria
V
Gregory
Alan J
AJ
Hay
John W
JW
McCauley
Colin A
CA
Russell
Derek J
DJ
Smith
Andrew
A
Rambaut
D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019143:Evolution, Molecular; D040961:Genetic Drift; D005838:Genotype; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D008957:Models, Genetic; D010641:Phenotype; D010802:Phylogeny; D012621:Seasons; D013997:Time Factors; D014774:Virulence
D000956:Antigens, Viral; D007252:Influenza Vaccines
Bayesian inference; antigenic cartography; evolution; influenza; multidimensional scaling; phylogenetics