Evolution of H3N2 Influenza Virus in a Guinea Pig Model 英文参考文献.docVIP

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Evolution of H3N2 Influenza Virus in a Guinea Pig Model 英文参考文献.doc

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Evolution of H3N2 Influenza Virus in a Guinea Pig Model 英文参考文献

EvolutionofH3N2InfluenzaVirusinaGuineaPigModel JinxueLong1¤,RuthV.Bushnell1,JohnK.Tobin1,KeyaoPan2,MichaelW.Deem2,PeterL.Nara1,3, GregoryJ.Tobin1,3 * 1BiologicalMimetics,Inc.,Frederick,Maryland,UnitedStatesofAmerica,2DepartmentofBioengineeringandPhysicsandAstronomy,RiceUniversity,Houston,Texas, UnitedStatesofAmerica,3DepartmentofBiologicalSciences,CollegeofVeterinaryMedicine,IowaStateUniversity,Ames,Iowa,UnitedStatesofAmerica Abstract Studiesofinfluenzavirus evolutionundercontrolled experimentalconditionscanprovideabetterunderstandingofthe consequences of evolutionary processes with and without immunological pressure. Characterization of evolved strains assistsinthedevelopmentofpredictivealgorithmsforboththeselectionofsubtypesrepresentedintheseasonalinfluenza vaccineandthedesignofnovelimmunerefocusedvaccines.Toobtaindataontheevolutionofinfluenzainacontrolled setting,na?¨veandimmunizedGuineapigswereinfectedwithinfluenzaA/Wyoming/2003(H3N2).Virusprogenyfromnasal washsampleswereassessedforvariationinthedominantandotherepitopesbysequencingthehemagglutinin(HA)gene toquantifyevolutionarychanges.ViralRNAfromthenasalwashesfrominfectionofna?¨veandimmuneanimalscontained 6% and 24.5% HA variant sequences, respectively. Analysis of mutations relative to antigenic epitopes indicated that adaptiveimmunityplayedakeyroleinvirusevolution.HAmutationsinimmunizedanimalswereassociatedwithlossof glycosylationandchangesinchargeandhydrophobicityinandnearresidueswithinknownepitopes.FourregionsofHA-1 (75–85,125–135,165–170,225–230)containedresiduesofhighestvariability.Thesesitesareadjacenttoorwithinknown epitopesandappeartoplayanimportantroleinantigenicvariation.Recognitionoftheroleofthesesitesduringevolution willleadtoabetterunderstandingofthenatureofevolutionwhichhelpinthepredictionoffuturestrainsforselectionof seasonal vaccines and the design of novel vaccines intended to stimulated broadened cross-reactive protection to conservedsitesoutsideofdominantepitopes. Citation: Long J, Bushn