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1、LETTERdoi:10.1038/nature12005Dipeptidylpeptidase4isafunctionalreceptorfortheemerginghumancoronavirus-EMC121,34565V.StalinRaj*,HuihuiMou*,SaskiaL.Smits,DickH.W.Dekkers,MarcelA.Mu¨ller,RonaldDijkman,DoreenMuth,4716,852JeroenA.A.Demmers,AliZaki,RonA.M.Fouchier,VolkerThi
2、el,ChristianDrosten,PeterJ.M.Rottier,121AlbertD.M.E.Osterhaus,BerendJanBosch&BartL.Haagmans10Mosthumancoronavirusescausemildupperrespiratorytractdis-antigen-relatedcelladhesionmolecules(CEACAM)toentercells,easebutmaybeassociatedwithmoreseverepulmonarydiseaseinwhereas
3、forseveralAlpha-andBetacoronaviruses,twopeptidases1immunocompromisedindividuals.However,SARScoronavirushavebeenidentifiedasreceptors(aminopeptidaseN(APN,CD13)causedseverelowerrespiratorydiseasewithnearly10%mortality11,12forhCoV-229Eandseveralanimalcoronaviruses,andan
4、giotensin2andevidenceofsystemicspread.Recently,anothercoronavirus(humancoronavirus-ErasmusMedicalCenter(hCoV-EMC))wasidentifiedinpatientswithsevereandsometimeslethallowerres-a)]Vero–1piratorytractinfection3,4.Viralgenomeanalysisrevealedclose9ml8relatednesstocoronavir
5、usesfoundinbats5.Hereweidentify507dipeptidylpeptidase4(DPP4;alsoknownasCD26)asafunctional65receptorforhCoV-EMC.DPP4specificallyco-purifiedwiththe4receptor-bindingS1domainofthehCoV-EMCspikeproteinfrom3Relativecellnumberlog[GE(TCID02040lysatesofsusceptibleHuh-7cells.An
6、tibodiesdirectedagainst0101102103104DPP4inhibitedhCoV-EMCinfectionofprimaryhumanbronchialb)]epithelialcellsandHuh-7cells.ExpressionofhumanandbatCOS-7–19(Pipistrelluspipistrellus)DPP4innon-susceptibleCOS-7cellsml850enabledinfectionbyhCoV-EMC.Theuseoftheevolutionarily7
7、6conservedDPP4proteinfromdifferentspeciesasafunctional5receptorprovidescluesaboutthehostrangepotentialofhCoV-43EMC.Inaddition,itwillcontributecriticallytoourunderstanding0Relativecellnumber101102103104log[GE(TCID02040ofthepathogenesisandepidemiologyofthisemerginghuma
8、ncoronavirus,andmayfacilitatethedevelopmentofinterventioncHuh-7)]strategies.–19Coronavirusesinfectawiderangeofmammalsandbirds.Their
