Chikungunya Virus Infection Results in Higher and Persistent Viral Replication in Aged Rhesus Macaques Due to Defects in Anti-Viral Immunity.docVIP

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Chikungunya Virus Infection Results in Higher and Persistent Viral Replication in Aged Rhesus Macaques Due to Defects in Anti-Viral Immunity.doc

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Chikungunya Virus Infection Results in Higher and Persistent Viral Replication in Aged Rhesus Macaques Due to Defects in Anti-Viral Immunity

ChikungunyaVirusInfectionResultsinHigherand PersistentViralReplicationinAgedRhesusMacaques DuetoDefectsinAnti-ViralImmunity IlhemMessaoudi1,2,3¤*,JenniferVomaske1,2,ThomasTotonchy2,CraigN.Kreklywich1, KristenHaberthur1,2,3,LauraSpringgay1,3,JamesD.Brien4,MichaelS.Diamond4,VictorR.DeFilippis1,3, DanielN.Streblow1,2,3 * 1VaccineandGeneTherapyInstitute,OregonHealthandScienceUniversity,Beaverton,Oregon,UnitedStatesofAmerica,2MolecularMicrobiologyandImmunology, Oregon Health and Science University, Portland, Oregon, United States of America, 3Division of Pathobiology and Immunology, Oregon National Primate Research Center,Beaverton,Oregon,UnitedStatesofAmerica,4DepartmentsofMolecularMicrobiology,Medicine,PathologyandImmunology,WashingtonUniversitySchoolof Medicine,St.Louis,Missouri,UnitedStatesofAmerica Abstract Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia,nauseaandrash.ThedistinguishingfeatureofCHIKVinfectionistheseveredebilitatingpoly-arthralgiathatmay persistforseveralmonthsafterviralclearance.Sinceitsre-emergence in2004,CHIKVhasspreadfromtheIndianOcean regiontonewlocationsincludingmetropolitanEurope,Japan,andeventheUnitedStates.TheriskofimportingCHIKVto newareasoftheworldisincreasingduetohighlevelsofviremiaininfectedindividualsaswellastherecentadaptationof thevirustothemosquitospeciesAedesalbopictus.CHIKVre-emergenceisalsoassociatedwithnewclinicalcomplications includingseveremorbidityand,forthefirsttime,mortality.Inthisstudy,wecharacterizeddiseaseprogressionandhost immuneresponsesinadultandagedRhesusmacaquesinfectedwitheithertherecentCHIKVoutbreakstrainLaReunion (LR)ortheWestAfricanstrain37997.Ourresultsindicatethatfollowingintravenousinfectionandregardlessofthevirus used, Rhesus macaques become viremic between days 1–5 post infection. While adult animals are able to control viral infection,agedanimalsshowpersistentvirusinthespleen.Virus-specificTcellresponsesintheagedanimalswerere