Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation 英文参考文献.docVIP

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Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation 英文参考文献.doc

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Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation 英文参考文献

FullFactorialAnalysisofMammalianandAvianInfluenza PolymeraseSubunitsSuggestsaRoleofanEfficient PolymeraseforVirusAdaptation OliveT.W.Li1,MichaelC.W.Chan1,CynthiaS.W.Leung1,ReneeW.Y.Chan1,YiGuan1,JohnM. Nicholls2,LeoL.M.Poon1* 1StateKeyLaboratoryofEmergingInfectiousDiseases,DepartmentofMicrobiology,TheUniversityofHongKong,HongKongSAR,China,2DepartmentofPathology, TheUniversityofHongKong,HongKongSAR,China Abstract Amongstalltheinternalgenesegments(PB2.PB1,PA,NP,MandNS),theavianPB1segmentistheonlyonewhichwas reassortedintothehumanH2N2andH3N2pandemicstrains.Thissuggeststhatthereassortmentofpolymerasesubunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis,wetestedthecompatibilitybetweenPB2,PB1,PAandNPderivedfromaH5N1virusandamammalianH1N1 virus.All16possiblecombinationsofavian-mammalianchimericviralribonucleoproteins(vRNPs)werecharacterized.We showedthatrecombinantvRNPswithamammalianPB2andanavianPB1hadthestrongestpolymeraseactivitiesinhuman cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures,especiallyatahighincubationtemperature.Theseviruseswerepotentinducersofproinflammatorycytokinesand chemokinesinprimaryhumanmacrophagesandpneumocytes.ViruseswiththisspecificPB2-PB1combinationwerealso foundtobemorecapabletogenerateadaptivemutationsunderanewselectionpressure.Theseresultssuggestedthatthe viralpolymeraseactivitymightberelevantforthegenesisofinfluenzavirusesofhumanhealthconcern. Citation: Li OTW, Chan MCW, Leung CSW, Chan RWY, Guan Y, et al. (2009) Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits SuggestsaRoleofanEfficientPolymeraseforVirusAdaptation.PLoSONE4(5):e5658.doi:10.1371/journal.pone.0005658 Editor:DingXiangLiu,InstituteofMolecularandCellBiology,Singapore ReceivedFebruary5,2009;AcceptedApril16,2009;PublishedMay21,2009 Copyright:?2009Lietal.Thisisanopen-accessarticledistributedund