title: Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans.
abstract: Human influenza A (subtype H3N2) is characterized genetically by the limited standing diversity of its hemagglutinin and antigenically by clusters that emerge and replace each other within 2 to 8 years. By introducing an epidemiological model that allows for differences between the genetic and antigenic properties of the virus's hemagglutinin, we show that these patterns can arise from cluster-specific immunity alone. Central to the formulation is a genotype-to-phenotype mapping, based on neutral networks, with antigenic phenotypes, not genotypes, determining the degree of strain cross-immunity. The model parsimoniously explains well-known, as well as previously unremarked, features of interpandemic influenza dynamics and evolution. It captures the observed boom-and-bust pattern of viral evolution, with periods of antigenic stasis during which genetic diversity grows, and with episodic contraction of this diversity during cluster transitions.
authors.affiliation: Department of Ecology and Evolutionary Biology, 2019 Kraus Natural Science Building, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109-1048, USA. kkoelle@psu.edu
authors.forename: Katia
authors.initials: K
authors.lastname: Koelle
authors.forename: Sarah
authors.initials: S
authors.lastname: Cobey
authors.forename: Bryan
authors.initials: B
authors.lastname: Grenfell
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pascual
mesh_terms: D019943:Amino Acid Substitution; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D003198:Computer Simulation; D003429:Cross Reactions; D004196:Disease Outbreaks; D004198:Disease Susceptibility; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D005838:Genotype; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D032521:Immunity, Herd; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology* / Q000635:transmission / Q000821:virology; D008954:Models, Biological; D015233:Models, Statistical; D010641:Phenotype; D010802:Phylogeny; D017354:Point Mutation; D011110:Polymorphism, Genetic
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus