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1、JOURNALOFVIROLOGY,Jan.2010,p.11981205Vol.84,No.20022-538X/10/$12.00doi:10.1128/JVI.01248-09Copyright©2010,AmericanSocietyforMicrobiology.AllRightsReserved.DifferentialDownregulationofACE2bytheSpikeProteinsofSevereAcuteRespiratorySyndromeCoronavirusandHumanCoronavirusNL63112,
2、321IlonaGlowacka,StephanieBertram,PetraHerzog,SusannePfefferle,ImkeSteffen,4456MarcusO.Muench,GrahamSimmons,HeikeHofmann,ThomasKuri,678FriedemannWeber,JuttaEichler,ChristianDrosten,1andStefanPo¨hlmann*1InstituteofVirology,HannoverMedicalSchool,30625Hannover,Germany;BernhardNo
3、chtInstituteforTropicalMedicine,23Bernhard-Nocht-Str.74,20359Hamburg,Germany;QiagenHamburgGmbH,Ko¨nigstr.4a,22767Hamburg,Germany;BloodSystemsResearchInstituteandDepartmentofLaboratoryMedicine,UniversityofCalifornia,SanFrancisco,45California;DepartmentofMedicalMicrobiologyandV
4、irology,UniversityofKiel,24105Kiel,Germany;6DepartmentofVirology,UniversityofFreiburg,79008Freiburg,Germany;DepartmentofMedicinalChemistry,7UniversityofErlangen-Nu¨rnberg,Schuhstrasse19,91052Erlangen,Germany;andInstituteof8Virology,UniversityofBonnMedicalCentre,Sigmund-Freud-
5、St.25,53127Bonn,GermanyReceived16June2009/Accepted16October2009Thehumancoronaviruses(CoVs)severeacuterespiratorysyndrome(SARS)-CoVandNL63employangio-tensin-convertingenzyme2(ACE2)forcellentry.ItwasshownthatrecombinantSARS-CoVspikeprotein(SARS-S)downregulatesACE2expressionandt
6、herebypromoteslunginjury.WhetherNL63-Sexertsasimilaractivityisyetunknown.WefoundthatrecombinantSARS-SboundtoACE2andinducedACE2sheddingwithhigherefficiencythanNL63-S.SheddingmostlikelyaccountedforthepreviouslyobservedACE2downregu-lationbutwasdispensableforviralreplication.Final
7、ly,SARS-CoVbutnotNL63replicatedefficientlyinACE2-positiveVerocellsandreducedACE2expression,indicatingrobustreceptorinterferenceinthecontextofSARS-CoVbutnotNL63infection.Severeacuterespiratorysyndromecoronavirus(SARS-ACE2isacomponentoftherenin-angiotensinsystem,CoV)emergedin200
8、2inGuangdongprovince,China,anditswhichregulatesbloodpressure(14,17).