Anti-Nucleocapsid Protein Immune Responses Counteract Pathogenic Effects of Rift Valley Fever Virus Infection in Mice 英文参考文献.docVIP

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Anti-Nucleocapsid Protein Immune Responses Counteract Pathogenic Effects of Rift Valley Fever Virus Infection in Mice 英文参考文献.doc

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Anti-Nucleocapsid Protein Immune Responses Counteract Pathogenic Effects of Rift Valley Fever Virus Infection in Mice 英文参考文献

Anti-NucleocapsidProteinImmuneResponses CounteractPathogenicEffectsofRiftValleyFeverVirus InfectioninMice PetrusJansenvanVuren1,2,CarolineT.Tiemessen2,3,JanuszT.Paweska1,2 * 1SpecialPathogensUnit,NationalInstituteforCommunicableDiseasesoftheNationalHealthLaboratoryService,Sandringham,SouthAfrica, 2DivisionVirologyand CommunicableDiseasesSurveillance,SchoolofPathology,UniversityoftheWitwatersrand,Johannesburg,SouthAfrica,3CellBiology/AIDSVirusResearchUnit,National InstituteforCommunicableDiseasesoftheNationalHealthLaboratoryService,Sandringham,SouthAfrica Abstract TheknownvirulencefactorofRiftValleyfevervirus(RVFV),theNSsprotein,counteractstheantiviraleffectsofthetypeI interferonresponse.Inthisstudyweevaluatedtheexpressionofseveralgenesintheliverandspleeninvolvedininnateand adaptiveimmunityofmiceimmunizedwithaRVFVrecombinantnucleocapsidprotein(recNP)combinedwithAlhydrogel adjuvant and control animals after challenge with wild type RVFV. Mice immunized with recNP elicited an earlier IFNb responseafterchallengecomparedtonon-immunizedcontrols.Intheacutephaseofliverinfectioninnon-immunizedmice there was a massive upregulation of type I and II interferon, accompanied by high viral titers, and the up- and downregulation of several genes involved in the activation of B- and T-cells, indicating that both humoral and cellular immunity is modulated during RVFV infection. Various genes involved in pro-inflammatory responses and with pro- apoptoticeffectswerestronglyupregulatedandanti-apoptoticgenesweredownregulatedinliverofnon-immunizedmice. ExpressionofmanygenesinvolvedinB-andT-cellimmunityweredownregulatedinspleenofnon-immunizedmicebut normalinimmunizedmice.Astrongbiastowardsapoptosisandinflammationinnon-immunizedmiceatanacutestageof liver infection associated with suppression of several genes involved in activation of humoral and cellular immunity in spleen,suggeststhatRVFVevadesthehostimmuneresponseinmorewaysthanonlybyinhibitionoftypeIinterferon,and thatimmunopat