  Seasonal influenza kills hundreds of thousands every year, with multiple
constantly-changing strains in circulation at any given time. A high mutation
rate enables the influenza virus to evade recognition by the human immune
system, including immunity acquired through past infection and vaccination.
Here, we capture the genetic similarity of influenza strains and their
evolutionary dynamics with genotype networks. We show that the genotype
networks of influenza A (H3N2) hemagglutinin are characterized by heavy-tailed
distributions of module sizes and connectivity, suggesting critical-like
behavior. We argue that: (i) genotype networks are driven by mutation and host
immunity to explore a subspace of networks predictable in structure, and (ii)
genotype networks provide an underlying structure necessary to capture the rich
dynamics of multistrain epidemic models. In particular, inclusion of
strain-transcending immunity in epidemic models is dependent upon the structure
of an underlying genotype network. This interplay suggests a self-organized
criticality where the epidemic dynamics of influenza locates critical-like
regions of its genotype network. We conclude that this interplay between
disease dynamics and network structure might be key for future network analysis
of pathogen evolution and realistic multistrain epidemic models.
