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F11-Mediated Inhibition of RhoA Signalling Enhances the Spread of Vaccinia Virus In Vitro and In Vivo in an Intranasal Mouse Model of Infection 英文参考文献.docVIP

F11-Mediated Inhibition of RhoA Signalling Enhances the Spread of Vaccinia Virus In Vitro and In Vivo in an Intranasal Mouse Model of Infection 英文参考文献.doc

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F11-Mediated Inhibition of RhoA Signalling Enhances the Spread of Vaccinia Virus In Vitro and In Vivo in an Intranasal Mouse Model of Infection 英文参考文献

F11-MediatedInhibitionofRhoASignallingEnhancesthe SpreadofVacciniaVirusInVitroandInVivoinan IntranasalMouseModelofInfection Joa?oV.Cordeiro1,SusanaGuerra2,3,YoshikiArakawa1,4,MarkP.Dodding1,MarianoEsteban2 ,Michael Way1* 1Cell Motility Laboratory, London Research Institute, London, United Kingdom, 2Department of Molecular and Cellular Biology, Centro Nacional de Biotecnolog?′a, Madrid,Spain,3DepartmentofPreventiveMedicineandPublicHealth,UniversidadAuto′noma,Madrid,Spain,4DepartmentofNeurosurgery,KyotoUniversityGraduate SchoolofMedicine,Kyoto,Japan Abstract The cortical actin cytoskeleton beneath the plasma membrane represents a physical barrier that vaccinia virus has to overcomeduringitsexitfromaninfectedcell.Previousobservationsusingoverexpressionandpharmacologicalapproaches suggestthatvacciniaenhancesitsreleasebymodulatingthecorticalactincytoskeletonbyinhibitingRhoAsignallingusing theviralproteinF11.WehavenowexaminedtheroleofF11anditsabilitytointeractwithRhoAtoinhibititsdownstream signallinginthespreadofvacciniainfectionbothinvitroandinvivo.Livecellimagingover48hoursrevealsthatlossofF11 oritsabilitytobindRhoAdramaticallyreducestherateofcell-to-cellspreadofthevirusinacellmonolayer.Cellsinfected with the DF11L virus also maintained their cell-to-cell contacts, and did not undergo virus-induced motility as observed duringwild-typeinfections.TheDF11Lvirusisalsoattenuatedinintranasalmousemodelsofinfection,asitisimpairedinits ability to spread from the initial sites of infection to the lungs and spleen. Loss of the ability of F11 to bind RhoA also reducesviralspreadinvivo.Ourresultsclearlyestablishthatviral-mediatedinibitionofRhoAsignallingcanenhancethe spreadofinfectionnotonlyincellmonolayers,butalsoinvivo. Citation:CordeiroJV,GuerraS,ArakawaY,DoddingMP,EstebanM,etal.(2009)F11-MediatedInhibitionofRhoASignallingEnhancestheSpreadofVaccinia VirusInVitroandInVivoinanIntranasalMouseModelofInfection.PLoSONE4(12):e8506.doi:10.1371/journal.pone.0008506 Editor:RobinCharlesMay,

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