Ezrin Interacts with the SARS Coronavirus Spike Protein and Restrains Infection at the Entry Stage.docx

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1、EzrinInteractswiththeSARSCoronavirusSpikeProteinandRestrainsInfectionattheEntryStageEzrinInteractswiththeSAKSCoronavirusSpikeProteinandRestrainSlnfectionattheEntryStageJeanKaoruMillet1,2a,FrancoisKien1,Chung-YanCheung4,Yu-1.amSiu1,Wing-1.imChan1,3,Huiying1.i1,Hiu-1.an1.eung1,4lMartialJaume1,RobertoB

2、ruzzone1,5,JosephS.MalikPeiris1,4,RalfMariusAltmeyer6,1,2bBeatriceNal*IHKU-PasteurResearchCentre,SchoolofEublicHealth,TheUniversiIyofHongKong,HongKongSAR,China,2DepartmentofAnatomy,SchoolofPublicHealth,ThelIniversityofHongKong,HongKongSAR,China,3DePartmentofPathology,SchoolofPublicHealth,TheUniversi

3、tyoflIongKong,HongKongSAR,China,4CentreofInfluenzaResearch,SchoolofPublicHealth,TheUniversityof!longKong,HongKongSAR,China,5DepartmentofCellBiologyandInfection,InstitutPasteur,Paris,Erance,61nstitutPasterofShanghai,Chinese1AcademyofSciences,Shanghai,ChinaAbstractBackground:EntryofSevereACUteReSPirat

4、OrySyndromecoronavirus(SAKS-CoV)anditsenvelopefusionwithhostcelImembranearecontrolledbyaseriesofcomplexmolecularmechanisms,largelydependentontheviralenvelopeglycoproteinSpike(三).Thcrearesti11manyunknownsontheimplicationofcelIularfactorsthatregulatetheentryprocess.MethodologyZPrincipalFindings:Wepcrf

5、ormedayeasttwo-hybridscreenusingasbaitthecarboxy-terminalendodomainofS,whichfacesthecyIosolduringandafteropeningoCthcfusionporeatcarIystagesofthevirus1ifecycle.Hereweshowthattheezrinmembrane-actiniInkerinteractswithScndodomainthroughthcF11obeofitsFERMdomainanclthatboththeeightcarboxy-ter11inalamino-

6、acidsanda11cmbrane-proxImalcysteineclUsterofSendodomainareimportantforthisinteractioninvitro.Interestingly,Wefoundthatezrinispresenta11hesiteofentryofS-pseudotypedIentiviralpartic1esinVeroE6cells.TargetingezrinfunctionbysmallinterferingRNincreasedS-mcdiatcdentryofpseudotypedparticlesinepithelialcells.Furthermore,deletionoftheeightcarboxy-terminalaminoacidsofSenhancedS-pseudotypedparticlesinfection.ExpressionoftheezrindominanIncgativeFERMdomainenhancedcelIsusceptibi1itytoinfectionbySRS-CoVandS-pseu.