  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.
