Research Article

Epochal Evolution Shapes the Phylodynamics of Interpandemic Influenza A (H3N2) in Humans

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Science  22 Dec 2006:
Vol. 314, Issue 5807, pp. 1898-1903
DOI: 10.1126/science.1132745

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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.

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