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1、DNAANDCELLBIOLOGYVolume24,Number8,2005?MaryAnnLiebert,Inc.Pp.496–502ApoptosisInducedbytheSARS-AssociatedCoronavirusinVeroCellsIsReplication-DependentandInvolvesCaspaseLILIREN,1,*RENQUANYANG,1,2,*LIGUO,1JIANGUOQU,1JIANWEIWANG,1andTAOHUNG1ABSTRACTThepathogenesisoftheseve
2、reacuterespiratorysyndrome(SARS),anewlyemerginglife-threateningdiseaseinhumans,remainsunknown.Itisbelievedthatthemodulationofapoptosisisrelevanttodiseasesthatarecausedbyvariousviruses.ToexaminepotentialapoptoticmechanismsrelatedtoSARS,weinvestigatedfea-turesofapoptosis
3、inducedbytheSARS-associatedcoronavirus(SARS-CoV)inhostcells.Theresultsindi-catedthattheSARS-CoV-inducedapoptosisinVerocellsinavirusreplication-dependentmanner.Addi-tionally,thedownregulationofBcl-2,theactivationofcasapse3,aswellastheupregulationofBaxweredetected,sugges
4、tingtheinvolvementofthecaspasefamilyandtheactivationofthemitochondrialsignalingpathway.Althoughthereisapositivecorrelationbetweenapoptosisandvirusreplication,thelatterisnotsig-nificantlyblockedbytreatmentwiththecaspaseinhibitorz-DEVD-FMK.Thesepreliminarydataprovideim-p
5、ortantinformationonboththepathogenesisandpotentialantiviraltargetsofSARS-CoV.INTRODUCTIONmembraneblebbing,cellshrinkage,andcompartmentalizationofthedeadcellsintomembrane-enclosedvesiclesorapoptoticPOPTOSIS,ORPROGRAMMEDCELLDEATH,isamorphologi-bodies(ArendsandWellie,1991
6、).SeveraldifferentcellularAcalandbiochemicallydefinedformofcelldeaththatoc-apoptosissignalingpathwaysareknownatpresent(Khosravi-cursinmanydiseasesincludingvirusinfections(Kerretal.,FarandEsposti2004;Thibodeauetal.,2004),andinmostin-1972;RazviandWelsh,1995).Itisbelieved
7、thatvirusesbe-stancesthecaspasesaredeemedascentralplayers.Caspaseslongingtodifferentfamilies,includingcoronaviruses,suchasareafamilyofcysteine-dependentaspartate-directedproteasesinfectiousbronchitisvirus(IBV;Liuetal.,2001),transmittedthatexistincellsasinactivezymogens
8、andaretriggeredtogastroenteritisvirus(TGEV;Eleouetetal.,1998),andmurinecleaveasetofproteinsatspecificsitescontaininga
