Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus 英文参考文献.docVIP

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Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus 英文参考文献.doc

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Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus 英文参考文献

ProgressionofPathogenicEventsinCynomolgus MacaquesInfectedwithVariolaVirus VictoriaWahl-Jensen1.,JenniferA.Cann1.,KathleenH.Rubins2,JohnW.Huggins3,RobertW.Fisher3, AnthonyJ.Johnson1,FabiandeKok-Mercado1,ThomasLarsen3,JoLynneRaymond3,LisaE.Hensley3, PeterB.Jahrling1* 1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, United States of America, 2Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3United States ArmyMedicalResearchInstituteofInfectiousDiseases,FortDetrick,Maryland,UnitedStatesofAmerica Abstract Smallpox,causedbyvariolavirus(VARV),isadevastatinghumandiseasethataffectedmillionsworldwideuntiltheviruswas eradicatedinthe1970s.Subsequentcessationofvaccinationhasresultedinanimmunologicallynaivehumanpopulation that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccinestocounterthisthreatwouldbefacilitatedbythedevelopmentofanimalmodelsusingauthenticVARV.Towards thisend,cynomolgusmacaqueswereidentifiedasadequatehostsforVARV,developingordinaryorhemorrhagicsmallpox inadose-dependentfashion.Tofurtherrefinethismodel,weperformedaserialsamplingstudyonmacaquesexposedto doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereaslymphocytolysisandhematopoieticnecrosisdevelopedinhemorrhagicsmallpox.Viralantigenaccumulation,as assessedimmunohistochemically,wasmildandtransientintheordinarysmallpoxmodel.Incontrast,inthehemorrhagic modelantigendistributionwaswidespreadandincludedtissuesandcellsnotinvolvedintheordinarymodel.Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historica