Abstract
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.
Highlights
Seasonal influenza infects between 10% and 20% of the human population every year, causing an estimated 250,000 to 500,000 deaths annually (Influenza Fact sheet, 2009)
In the Bayesian multidimensional scaling (BMDS) model, a map distance of one antigenic unit translates to an expectation of a twofold drop in hemagglutination inhibition (HI) titer between virus and sera
We apply this model to HI measurements of virus isolates against post-infection ferret antisera for influenza A/H3N2, A/H1N1, B/Vic and B/Yam
Summary
Seasonal influenza infects between 10% and 20% of the human population every year, causing an estimated 250,000 to 500,000 deaths annually (Influenza Fact sheet, 2009). Even though the human immune system can detect and destroy the virus that causes influenza, people can catch flu many times throughout their lifetimes because the virus keeps evolving in an effort to avoid the immune system. This antigenic drift—so-called because the antigens displayed by the virus keep changing— explains why influenza vaccines become less effective over time and need to be reformulated every year
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