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1、REPORTSattenuatedwithanMLDof3.43103,caus-50MolecularBasisforHighingonlyrespiratoryinfection.Noneoftheothersingle-genereassortants,possessingonlyoneVirulenceofHongKongH5N1genefromHK483virusandtheremaininggenesfromHK486virus,wasasvirulentastheHK483virus(MLD,.102PFU).Th
2、esingle-50In?uenzaAVirusesgenereassortantspossessing486HA227IweremoreattenuatedthanthosepossessingMasatoHatta,1PengGao,1PeterHalfmann,1486HA227S.TheHK6HA227S/3NAandYoshihiroKawaoka1,2*HK6HA227I/3NAreassortants,possessingtheHK483NAgeneandallremaininggenesfromIn1997,an
3、H5N1in?uenzaAviruswastransmittedfrombirdstohumansinHK486(testedasrepresentativesofavirulentHongKong,killing6ofthe18peopleinfected.Whenmicewereinfectedwithsingle-genereassortantviruses),wererecoveredthehumanisolates,twovirulencegroupsbecameapparent.Usingreverseonlyfro
4、mrespiratoryorgans(Table1).Thesegenetics,weshowedthatamutationatposition627inthePB2proteinresultsindicatethatthePB2viralproteinisin?uencedtheoutcomeofinfectioninmice.Moreover,highcleavabilityoftheresponsibleforthedifferenceinvirulencebe-hemagglutininglycoproteinwasan
5、essentialrequirementforlethalinfection.tweenthetwoHongKongH5N1viruses,andthataSer-to-Ilesubstitutionatposition227ofAnoutbreakofH5N1influenzaAvirusin227S)andHK486RG(HA-227I)]didnotkilltheHK486HAcanreducethevirulencepoten-HongKongin1997resultedin6deathsamongmiceevenata
6、doseof103PFU,andbothtialofthevirus.18peopleinfected(1±3).ThevirulenceseeninwererecoveredonlyfromrespiratoryorgansThereareeightaminoaciddifferencesbe-micewheninfectedwiththesehumanisolates(Table1).However,theMLDforHK-tweenthePB2proteinsofHK483andHK48650showedsomecorre
7、spondencewiththeseverity486RG(HA-227S)was4.63104,whereasviruses(Fig.2).Toidentifythespecificchang-ofdiseaseinadultpatients,althoughthereareHK486RG(HA-227I)failedtokillmiceattheesthatgiverisetovirulence,wegeneratedexceptions(3±7).Todeterminethemolecularhighestdosetest
8、ed,1.33106PFU.mutantHK483virusespossessingachimericbasisforthedifferenceinvirulenceamongToelucidatethemolecularbasisofthevir-PB2pro
