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1、JOURNALOFVIROLOGY,Dec.2011,p.1336313372Vol.85,No.240022-538X/11/$12.00doi:10.1128/JVI.05300-11Copyright©2011,AmericanSocietyforMicrobiology.AllRightsReserved.CleavageandActivationoftheSevereAcuteRespiratorySyndromeCoronavirusSpikeProteinbyHumanAirwayTrypsin-LikeProtease1,21341StephanieBertram,Ilona
2、Glowacka,MarcelA.Mu¨ller,HayleyLavender,KerstinGnirss,23563IngaNehlmeier,DanielaNiemeyer,YuxianHe,GrahamSimmons,ChristianDrosten,7,891,61,2ElizabethJ.Soilleux,OlafJahn,ImkeSteffen,andStefanPo¨hlmann*12InstituteofVirology,HannoverMedicalSchool,Hannover,Germany;GermanPrimateCenter,Go¨ttingen,Germany;I
3、nstituteof3Virology,UniversityofBonnMedicalCentre,Bonn,Germany;Oxfabs,NuffieldDepartmentofClinicalLaboratorySciences,4JohnRadcliffeHospital,UniversityofOxford,Oxford,UnitedKingdom;InstituteofPathogenBiology,ChineseAcademyof5MedicalSciences,andPekingUnionMedicalCollege,Beijing,China;BloodSystemsResear
4、chInstituteand6DepartmentofLaboratoryMedicine,UniversityofCalifornia,SanFrancisco,California;Departmentof7CellularPathology,JohnRadcliffeHospital,Oxford,UnitedKingdom;NuffieldDepartmentofClinicalLaboratorySciences,JohnRadcliffeHospital,UniversityofOxford,8UnitedKingdom;andProteomicsGroup,MaxPlanckIns
5、tituteof9ExperimentalMedicine,Go¨ttingen,GermanyReceived6June2011/Accepted21September2011Thehighlypathogenicsevereacuterespiratorysyndromecoronavirus(SARS-CoV)posesaconstantthreattohumanhealth.Theviralspikeprotein(SARS-S)mediateshostcellentryandisapotentialtargetforantiviralintervention.Activationof
6、SARS-SbyhostcellproteasesisessentialforSARS-CoVinfectivitybutremainsincompletelyunderstood.Here,weanalyzedtheroleofthetypeIItransmembraneserineproteases(TTSPs)humanairwaytrypsin-likeprotease(HAT)andtransmembraneprotease,serine2(TMPRSS2),inSARS-Sactivation.WefoundthatHATactivatesSARS-Sinthecontextofs
7、urrogatesystemsandauthenticSARS-CoVinfectionandiscoexpressedwiththeviralreceptorangiotensin-convertingenzyme2(ACE2)inbronchialepithelialcellsandpneumocytes.HATcleavedSARS-SatR667,asdeterminedbymutagen
