title: Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans.
abstract: Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.
authors.affiliation: Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Pokfulam, Hong Kong Special Admnistrative Region, China. justin.bahl@duke-nus.edu.sg
authors.forename: Justin
authors.initials: J
authors.lastname: Bahl
authors.forename: Martha I
authors.initials: MI
authors.lastname: Nelson
authors.forename: Kwok H
authors.initials: KH
authors.lastname: Chan
authors.forename: Rubing
authors.initials: R
authors.lastname: Chen
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Vijaykrishna
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Halpin
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Stockwell
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.forename: David E
authors.initials: DE
authors.lastname: Wentworth
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
authors.forename: Steven
authors.initials: S
authors.lastname: Riley
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Gavin J D
authors.initials: GJ
authors.lastname: Smith
mesh_terms: D001208:Asia / Q000453:epidemiology; D044362:Australasia / Q000453:epidemiology; D001483:Base Sequence; D001499:Bayes Theorem; D003710:Demography; D004196:Disease Outbreaks; D005060:Europe / Q000453:epidemiology; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000502:physiology; D007251:Influenza, Human / Q000453:epidemiology*; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009518:New York / Q000453:epidemiology; D058974:Phylogeography; D011157:Population Dynamics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012621:Seasons; D017422:Sequence Analysis, DNA
references.citation: PLoS Pathog. 2006 Dec;2(12):e125
references.pmid: 17140286
references.citation: PLoS Pathog. 2007 Sep 14;3(9):1220-8
references.pmid: 17941707
references.citation: Science. 2006 Dec 22;314(5807):1898-903
references.pmid: 17185596
references.citation: PLoS Biol. 2006 May;4(5):e88
references.pmid: 16683862
references.citation: BMC Evol Biol. 2007 Nov 08;7:214
references.pmid: 17996036
references.citation: Emerg Infect Dis. 2007 Jul;13(7):1052-7
references.pmid: 18214178
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15124-9
references.pmid: 15477600
references.citation: PLoS Med. 2006 Apr;3(4):e89
references.pmid: 16509764
references.citation: Environ Health Perspect. 2011 Apr;119(4):439-45
references.pmid: 21097384
references.citation: Nature. 2009 Jun 25;459(7250):1122-5
references.pmid: 19516283
references.citation: J Virol. 2008 Jan;82(2):596-601
references.pmid: 17942553
references.citation: Mol Biol Evol. 2006 Jan;23(1):7-9
references.pmid: 16177232
references.citation: Mol Biol Evol. 2008 Jul;25(7):1459-71
references.pmid: 18408232
references.citation: Infect Genet Evol. 2008 May;8(3):239-46
references.pmid: 17921073
references.citation: PLoS Pathog. 2010 May 27;6(5):e1000918
references.pmid: 20523898
references.citation: Science. 2008 Apr 18;320(5874):340-6
references.pmid: 18420927
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3645-6
references.pmid: 19276125
references.citation: Nature. 2008 May 29;453(7195):615-9
references.pmid: 18418375
references.citation: Epidemiol Infect. 1998 Aug;121(1):121-8
references.pmid: 9747763
references.citation: Nat Rev Genet. 2007 Mar;8(3):196-205
references.pmid: 17262054
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3243-8
references.pmid: 19204283
references.citation: Vaccine. 2010 Feb 3;28(5):1156-67
references.pmid: 20004635
references.citation: PLoS Med. 2006 Apr;3(4):e121
references.pmid: 16515368
references.citation: PLoS Comput Biol. 2009 Sep;5(9):e1000520
references.pmid: 19779555