Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the AlphaBeta Interferon Receptor 英文参考文献.docVIP

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Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the AlphaBeta Interferon Receptor 英文参考文献.doc

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Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the AlphaBeta Interferon Receptor 英文参考文献

EstablishmentofaBluetongueVirusInfectionModelin MicethatAreDeficientintheAlpha/BetaInterferon Receptor EvaCalvo-Pinilla1,TeresaRodr?′guez-Calvo1,JuanAnguita2,Noem?′Sevilla1,JavierOrtego1* 1CentrodeInvestigacio′nenSanidadAnimal,CISA-INIA,Madrid,Spain,2DepartmentofVeterinaryandAnimalSciences,UniversityofMassachusettsAmherst,Amherst, Massachusetts,UnitedStatesofAmerica Abstract Bluetongue (BT) is a noncontagious, insect-transmitted disease of ruminants caused by the bluetongue virus (BTV). A laboratory animal model would greatly facilitate the studies of pathogenesis, immune response and vaccination against BTV.Herein,weshowthatadultmicedeficientintypeIIFNreceptor(IFNAR(2/2))arehighlysusceptibletoBTV-4andBTV-8 infectionwhenthevirusisadministeredintravenously.Diseasewascharacterizedbyoculardischargesandapathy,starting at 48hours post-infection and quickly leading to animal death within 60hours of inoculation. Infectious virus was recovered from the spleen, lung, thymus, and lymph nodes indicating a systemic infection. In addition, a lymphoid depletion in spleen, and severe pneumonia were observed in the infected mice. Furthermore, IFNAR(2/2) adult mice immunizedwithaBTV-4inactivatedvaccineshowedtheinductionofneutralizingantibodiesagainstBTV-4andcomplete protection against challenge with a lethal dose of this virus. The data indicate that this mouse model may facilitate the studyofBTVpathogenesis,andthedevelopmentofneweffectivevaccinesforBTV. Citation:Calvo-PinillaE,Rodr?′guez-CalvoT,AnguitaJ,SevillaN,OrtegoJ(2009)EstablishmentofaBluetongueVirusInfectionModelinMicethatAreDeficientin theAlpha/BetaInterferonReceptor.PLoSONE4(4):e5171.doi:10.1371/journal.pone.0005171 Editor:CherylA.Stoddart,UniversityofCalifornia,SanFrancisco,UnitedStatesofAmerica ReceivedDecember6,2008;AcceptedMarch12,2009;PublishedApril9,2009 Copyright:?2009Calvo-Pinillaetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution