SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b.docx

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1、SARSCoronavirus3bAccessoryProteinModulatesTranscriptionalActivityofRUNXlbSAKSCoronavirus3bzccessoryProteinModlatesTranscriptionalActiviIyofRUNX1bBhavnaVarshney1 ,SudhakarAgnihotram2,Yee-JooTan3,KalphBaric2 ,SunilK.1.al1*IvirologyGroup,InternationalCentreforGeneticEngineeringandBiotechnology,NewDelhi

2、,India,2DepartmentofMiCrobiologyandImmunology,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3DepartmentofMicrobiology,Yong1.oo1.inSchoolofMedicine,NationalUniversityofSingapore,Singapore,SingaporeAbstractBackground:Thecausativeagentofsevereacuterespiratorysyndrome,SARScoro

3、navirus(SARS-CoV)genomeencodesseveraluniquegropspecificaccessoryproteinswithnknownfunctions.Amongthem,accessoryprotein3b(alsoknownasORF4)waslatelyidentifiedasoneoftheViralinterferonantagonist.Recentlyourlabuncoveredanewrolefor3binUpregulationofAp-Itranscriptionalactivityanditsdownstreanigenes.Thus,W

4、ebelievethatBbmightplayanimportantroleinSRS-CoVpatHogenesisandtKereforeisofconsiderableinterest.ThecurrentstudyaimsatidentifyingnovelhostCellularinteractorsoftheSbprotein.Methodology/PrincipalFindings:Inthisstudy,usingyeasttwo-hybridandco-immunoprecipitationtechniqucs,WChaVeidentifiedahosttranscript

5、IonfactorRUNXlb(RuntreIatedtranscriptionfactor,isoformb)asanovelinteractingpartnerforSRSCoV3bprotein.Chromatinimmunoprecipitaion(ChIP)andreportergcncassaysin3bexpressingjurkatcelIsshowedrccruitmcntof3bonthcRUNXIbindinge1cmcnIthatledtoanincreaseiIiRUNXlbtransactivationpotentialontheI1.2promoter.Kinas

6、eassayandpharmacologicalinhibiIortreatmentimpIiedthatBbalsoaffectRuNxibtranscriptionalactivitybyregulatingitsERKdependentphosphorylationlevels.Additionally,mRNlevelsofMIP-IataRUNXlbtargetgeneUpregulatedinSARS-CoVinfectedmonocytederiveddendriticcells,werefoundtobeelevatedin3bexpressingU937monocyIecelIs.Conclusions/Significanoe:Theseresultsunveilanove1interactionofSARS-CoV3bwiththehostfactor,RUNXlb,andspeculateitsphysiologicalrclevanceinupregulatingcytokineSandchemokinelevelsinstat.