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1、JGVPapersinPress.PublishedSeptember28,2013asdoi:10.1099/vir.0.055533-01JGVVIR/2013/055533Revised2Delayedinductionofproinflammatorycytokinesandsuppressionofinnateantiviralresponseby3thenovelMiddleEastRespiratorySyndromeCoronavirus:implicationsonpathogen

2、esisand4treatment51,2,3,44446SusannaK.P.Lau,CandyC.Y.Lau,Kwok-HungChan,ClaraP.Y.Li,HonglinChen,1,2,3,4541,2,3,41,2,3,4*7Dong-YanJin,JasperF.W.Chan,PatrickC.Y.Woo,andKwok-YungYuen819StateKeyLaboratoryofEmergingInfectiousDiseases,TheUniversityofHongKong,

3、Hong10Kong,China211ResearchCentreofInfectionandImmunology,TheUniversityofHongKong,HongKong,12China313CarolYuCentreforInfection,TheUniversityofHongKong,HongKong,China414DepartmentofMicrobiology,TheUniversityofHongKong,HongKong,China515DepartmentofBioche

4、mistry,TheUniversityofHongKong,HongKong,China1617Runningtitle:MERS-CoVcytokineresponses1819Keyword:human,coronavirus,MERS,SARS,229E,cytokine,proinflammatory,innate,20immune,mRNA21ContentCategory:AnimalRNAviruses22Abstract:250words23Maintext:4077words(i

5、ncludingfigurelegends)124Table:125Figure:4*26Correspondingauthor.Mailingaddress:StateKeyLaboratoryofEmergingInfectiousDiseases,27DepartmentofMicrobiology,TheUniversityofHongKong,Room423,UniversityPathology28Building,QueenMaryHospital,HongKongSpecialAdm

6、inistrativeRegion,China.Phone:29(852)22554892.Fax:(852)28551241.E-mail:kyyuen@hkucc.hku.hk30231ABSTRACT32ThehighmortalityassociatedwiththenovelMiddleEastRespiratorySyndromeCoronavirus33(MERS-CoV)hasraisedquestionsonthepossibleroleofcytokinestorminitspa

7、thogenesis.34AlthoughrecentstudiesshowedthatMERS-CoVinfectionisassociatedwithattenuated35interferonresponse,noinductionofinflammatorycytokineswasdemonstratedduringearly36phaseofinfection.TostudybothearlyandlatecytokineresponsesassociatedwithMERS-CoV37i

8、nfection,wemeasuredthemRNAlevelsofeightcytokinegenes(TNF-α,IL-1β,IL-6,IL-8,38IFN-β,MCP-1,TGF-βandIP-10)incelllysatesofpolarizedairwayepithelial,Calu-3,cells39infectedwithMERS-CoVorSARS-CoVupto30hpostinfection.Amongtheeightcytokine40gene