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
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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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