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Science 22 December 2006:
Vol. 314. no. 5807, pp. 1898 - 1903
DOI: 10.1126/science.1132745
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Research Articles

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

Katia Koelle,1,2*{dagger} Sarah Cobey,1{dagger} Bryan Grenfell,2,3 Mercedes Pascual1

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.

1 Department of Ecology and Evolutionary Biology, 2019 Kraus Natural Science Building, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109-1048, USA.
2 Center for Infectious Disease Dynamics (CIDD), Department of Biology, 208 Mueller Lab, Eberly College of Science, The Pennsylvania State University (PSU), University Park, PA 16802, USA.
3 Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.

{dagger} These authors contributed equally to this work.

* To whom correspondence should be addressed. E-mail: kkoelle{at}psu.edu

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