Ebola Virus Genome Plasticity as a Marker of Its Passaging History A Comparison of In Vitro Passaging to Non-Human Primate Infection 英文参考文献.docVIP

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Ebola Virus Genome Plasticity as a Marker of Its Passaging History A Comparison of In Vitro Passaging to Non-Human Primate Infection 英文参考文献.doc

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Ebola Virus Genome Plasticity as a Marker of Its Passaging History A Comparison of In Vitro Passaging to Non-Human Primate Infection 英文参考文献

EbolaVirusGenomePlasticityasaMarkerofIts PassagingHistory:AComparisonofInVitroPassagingto Non-HumanPrimateInfection JeffreyR.Kugelman1,MichaelS.Lee1,6,CynthiaA.Rossi4,SarahE.McCarthy1,SheliR.Radoshitzky3, JohnM.Dye2,LisaE.Hensley2,AnnaHonko2,JensH.Kuhn5,PeterB.Jahrling5,TravisK.Warren3, ChrisA.Whitehouse1,SinaBavari3,GustavoPalacios1* 1Genomics Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, United States of America, 2Virology Division,UnitedStatesArmyMedicalResearchInstituteofInfectiousDiseases(USAMRIID),FortDetrick,Maryland,UnitedStatesofAmerica,3ToxicologyDivision,United StatesArmyMedicalResearchInstituteofInfectiousDiseases(USAMRIID),FortDetrick,Maryland,UnitedStatesofAmerica,4DiagnosticSystemsDivision,UnitedStates ArmyMedicalResearchInstituteofInfectiousDiseases(USAMRIID),FortDetrick,Maryland,UnitedStatesofAmerica,5IntegratedResearchFacilityatFortDetrick,National InstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth,FortDetrick,Maryland,UnitedStatesofAmerica,6SimulationSciencesBranch,UnitedStates ArmyResearchLaboratory,AberdeenProvingGround,Maryland,UnitedStatesofAmerica Abstract To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebolavirus(Kikwitvariant)invitroandinvivoandperformeddeepsequencinganalysisofthecompletegenomesofthe viralsubpopulations.WethendeterminedthesitesundergoingselectionduringpassageinVeroE6cells.Fourlocations withintheEbolavirusKikwitgenomewereidentifiedthattogethersegregatecellculture-passagedvirusandvirusobtained frominfectednon-humanprimates.Threeoftheidentifiedsitesarelocatedwithintheglycoproteingene(GP)sequence:the poly-U(RNAediting)site atposition6925,as wellaspositions6677, and6179.Onesitewas foundintheVP24gene at position10833.Inallcases,invitroandinvivo,bothpopulations(majorityandminorityvariants)weremaintainedinthe viral swarm, with rapid selections occurring after a few pas