SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b 英文参考文献.docVIP

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SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b 英文参考文献.doc

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SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b 英文参考文献

SARSCoronavirus3bAccessoryProteinModulates TranscriptionalActivityofRUNX1b BhavnaVarshney1,SudhakarAgnihotram2,Yee-JooTan3,RalphBaric2,SunilK.Lal1* 1VirologyGroup,InternationalCentreforGeneticEngineeringandBiotechnology,NewDelhi,India,2DepartmentofMicrobiologyandImmunology,UniversityofNorth Carolina, Chapel Hill, North Carolina, United States of America, 3Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore,Singapore Abstract Background: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes severaluniquegroupspecificaccessoryproteinswithunknownfunctions.Amongthem,accessoryprotein3b(alsoknown as ORF4) was lately identified as one of the viralinterferon antagonist. Recently our lab uncovered a new role for 3b in upregulationofAP-1transcriptionalactivityanditsdownstreamgenes.Thus,webelievethat3bmightplayanimportant roleinSARS-CoVpathogenesisandthereforeisofconsiderableinterest.Thecurrentstudyaimsatidentifyingnovelhost cellularinteractorsofthe3bprotein. Methodology/PrincipalFindings:Inthisstudy,usingyeasttwo-hybridandco-immunoprecipitationtechniques,wehave identifiedahosttranscriptionfactorRUNX1b(Runtrelatedtranscriptionfactor,isoformb)asanovelinteractingpartnerfor SARS-CoV3bprotein.Chromatinimmunoprecipitaion(ChIP)andreportergeneassaysin3bexpressingjurkatcellsshowed recruitmentof3bontheRUNX1bindingelementthatledtoanincreaseinRUNX1btransactivationpotentialontheIL2 promoter.Kinaseassayandpharmacologicalinhibitortreatmentimpliedthat3balsoaffectRUNX1btranscriptionalactivity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1a, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocytecells. Conclusions/Significance: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculateitsphysiologicalrelevanceinupregulatin