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1、JVIAcceptedManuscriptPostedOnline3June2015J.Virol.doi:10.1128/JVI.01029-15Copyright?2015,AmericanSocietyforMicrobiology.AllRightsReserved.1JVI01029-15-REVISEDVERSION23Forpublicationin4JournalofVirology56Akinome-widesiRNAscreenidentifiesproviralandantiviralhostfactorsinSARS-c

2、oronavirus7replication,includingPKRandearlysecretorypathwayproteins89Runningtitle:HostfactorsinSARS-CoVreplication10Keywords:nidovirus,hostproteins,immuneresponse,RNAiscreen,kinase,COPB2,COPI-coated11vesicles,severeacuterespiratorysyndrome121?1?12#313AdriaanH.deWilde,Kazimie

3、rF.Wannee,FlorineE.M.Scholte,JelleJ.Goeman,PetertenDijke,11?*1?*14EricJ.Snijder,MarjoleinKikkert,andMartijnJ.vanHemert15116MolecularVirologyLaboratory,DepartmentofMedicalMicrobiology,217DepartmentofMedicalStatistics,318DepartmentofMolecularCellBiology,CancerGenomicsCentreNet

4、herlandsandCentreforBiomedical19Genetics,20LeidenUniversityMedicalCenter,Leiden,TheNetherlands.21?,?22Theseauthorscontributedequally23#24Currentaddress:Biostatistics,DepartmentforHealthEvidence,RadboudUniversityMedicalCenter,25Nijmegen,TheNetherlands126*27Correspondingauthor

5、s:MartijnJ.vanHemertandMarjoleinKikkert,MolecularVirologyLaboratory,28DepartmentofMedicalMicrobiology,LeidenUniversityMedicalCenter,POBox9600,2300RCLeiden,29TheNetherlands.Phone:+31715261652,Fax:+31715266761.E-mail:m.j.van_hemert@lumc.nlor30m.kikkert@lumc.nl.313233Abstractwo

6、rdcount:25034Importancewordcount:15035Textwordcount:874236Tables:037Figures:938Supplementaldatasets:139References:10040241Abstract4243ToidentifyhostfactorsrelevantforSARS-coronavirus(SARS-CoV)replication,weperformedansiRNA44libraryscreentargetingthehumankinome.Proteinkinases

7、arekeyregulatorsofmanycellularfunctions45andthesystematicknockdownoftheirexpressionshouldprovideabroadperspectiveonfactorsand46pathwayspromotingorantagonizingcoronavirusreplication.Inadditionto40proteinsthatpromote47SARS-CoVreplication,ourstudyidentified90factorsexhibitingan

8、antiviraleffect.Pathwayanalysis48groupedsubsetsofthesefactorsinspecificcell