title: Stochastic processes are key determinants of short-term evolution in influenza a virus.
abstract: Understanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis.
authors.affiliation: Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Martha I
authors.initials: MI
authors.lastname: Nelson
authors.forename: Lone
authors.initials: L
authors.lastname: Simonsen
authors.forename: Cecile
authors.initials: C
authors.lastname: Viboud
authors.forename: Mark A
authors.initials: MA
authors.lastname: Miller
authors.forename: Jill
authors.initials: J
authors.lastname: Taylor
authors.forename: Kirsten St
authors.initials: KS
authors.lastname: George
authors.forename: Sara B
authors.initials: SB
authors.lastname: Griesemer
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedi
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Sengamalay
authors.forename: David J
authors.initials: DJ
authors.lastname: Spiro
authors.forename: Igor
authors.initials: I
authors.lastname: Volkov
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Grenfell
authors.forename: David J
authors.initials: DJ
authors.lastname: Lipman
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
mesh_terms: D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics; D019143:Evolution, Molecular; D051456:Gene Flow; D005814:Genes, Viral; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D009518:New York; D010802:Phylogeny; D011159:Population Surveillance; D013269:Stochastic Processes
chemical_list: D000956:Antigens, Viral