Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918 英文参考文献.docVIP

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Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918 英文参考文献.doc

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Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918 英文参考文献

EvolutionaryTrendsofA(H1N1)InfluenzaVirus HemagglutininSince1918 JunShen1,JianpengMa1,2*,QinghuaWang2* 1Department of Bioengineering, Rice University, Houston, Texas, United States of America, 2Department of Biochemistry and Molecular Biology, Baylor College of Medicine,Houston,Texas,UnitedStatesofAmerica Abstract ThePandemic(H1N1)2009isspreadingtonumerouscountriesandcausingmanyhumandeaths.Althoughthesymptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreakinsubsequentmonths.Astheprimaryimmunity-elicitingantigen,hemagglutinin(HA)isthemajoragentforhost- drivenantigenicdriftinA(H3N2)virus.However,whetherandhowtheevolutionofHAisinfluencedbyexistingimmunityis poorly understood for A(H1N1). Here, by analyzing hundreds of A(H1N1) HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1) HAs. Among a subgroup of human A(H1N1) HAs between 1918,2008,wefoundstrongdiversifying(positive)selectionatHA1156and190.Wealsoanalyzedtheevolutionarytrends atHA1190and225thatarecriticaldeterminantsforreceptor-bindingspecificityofA(H1N1)HA.DifferentA(H1N1)viruses appearedtofavoroneofthesetwositesinhost-drivenantigenicdrift:epidemicA(H1N1)HAsfavorHA1190whilethe1918 pandemic and swine HAs favor HA1 225. Thus, our results highlight the urgency to understand the interplay between antigenicdriftandreceptorbindinginHAevolution,andprovidemolecularsignaturesformonitoringfutureantigenically drifted2009pandemicandseasonalA(H1N1)influenzaviruses. Citation: Shen J, Ma J, Wang Q (2009) Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918. PLoS ONE 4(11): e7789. doi:10.1371/ journal.pone.0007789 Editor:DarrenP.Martin,InstituteofInfectiousDiseaseandMolecularMedicine,SouthAfrica ReceivedAugust7,2009;AcceptedOctober15,2009;PublishedNovember17,2009 Copyright: ? 2009 Shen et al. This is an open-access article distributed under the terms of the Creative Commons Attri