Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin 英文参考文献.docVIP

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Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin 英文参考文献.doc

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Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin 英文参考文献

PredictingtheAntigenicStructureofthePandemic (H1N1)2009InfluenzaVirusHemagglutinin ManabuIgarashi1,KimihitoIto1,ReikoYoshida1,DaisukeTomabechi1,HiroshiKida1,2,3,AyatoTakada1* 1DepartmentofGlobalEpidemiology,HokkaidoUniversityResearchCenterforZoonosisControl,Sapporo,Japan,2DepartmentofDiseaseControl,GraduateSchoolof VeterinaryMedicine,HokkaidoUniversity,Sapporo,Japan,3OIEReferenceLaboratoryforHighlyPathogenicAvianInfluenza,Sapporo,Japan Abstract Thepandemicinfluenza virus (2009H1N1)wasrecentlyintroduced intothehumanpopulation.Thehemagglutinin(HA) geneof2009H1N1isderivedfrom‘‘classicalswineH1N1’’virus,whichlikelysharesacommonancestorwiththehuman H1N1virusthatcausedthepandemicin1918,whosedescendantvirusesarestillcirculatinginthehumanpopulationwith highlyalteredantigenicityofHA.However,informationonthestructuralbasistocomparetheHAantigenicityamong2009 H1N1,the1918pandemic,andseasonalhumanH1N1viruseshasbeenlacking.ByhomologymodelingoftheHAstructure, hereweshowthatHAsof2009H1N1andthe1918pandemicvirusshareasignificantnumberofaminoacidresiduesin knownantigenicsites,suggestingtheexistenceofcommonepitopesforneutralizingantibodiescross-reactivetobothHAs. ItwasnotedthattheearlyhumanH1N1virusesisolatedinthe1930s–1940sstillharboredsomeoftheoriginalepitopesthat arealsofoundin2009H1N1.Interestingly,while2009H1N1HAlacksthemultipleN-glycosylationsthathavebeenfoundto beassociatedwithanantigenicchangeofthehumanH1N1virusduringtheearlyepidemicofthisvirus,2009H1N1HAstill retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the humanH1N1virus.Wethushypothesizethatthe2009H1N1HAantigenicsitesinvolvingtheconservedaminoacidswill soonbetargetedbyantibody-mediatedselectionpressureinhumans.Indeed,aminoacidsubstitutionspredictedhereare occurringintherecent2009H1N1variants.Thepresentstudysuggeststhatantibodieselicitedbynaturalinfectionwiththe 1918pandemicoritsearlydescendantvirusesplayaroleinspecificimmunityagainst2009H1N1,andprovidesan