An “Escape Clock” for Estimating the Turnover of SIV DNA in Resting CD4+ T Cells 英文参考文献.docVIP
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An“EscapeClock”forEstimatingtheTurnoverofSIVDNAinRestingCD4TCells英文参考文献
An‘‘EscapeClock’’forEstimatingtheTurnoverofSIV
DNAinRestingCD4+TCells
JeanetteReece1,JankaPetravic2,MehalaBalamurali2,LiyenLoh1,ShayaranaGooneratne1,RobDe
Rose1,StephenJ.Kent1.*,MilesP.Davenport2.
*
1Department ofMicrobiology andImmunology,UniversityofMelbourne,Parkville, Victoria, Australia, 2Centre forVascularResearch, UniversityofNew SouthWales,
Sydney,NewSouthWales,Australia
Abstract
Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most
studiessuggestthatcellswithlatentlyintegratedHIVdecayveryslowlyundertherapy.However,itismuchmoredifficultto
studytheturnoverandpersistenceofHIVDNAduringactiveinfection.Wehavedevelopedan‘‘escapeclock’’approachfor
measuringtheturnoverofHIVDNAinrestingCD4+Tcells.Thisapproachstudiesthereplacementofwild-type(WT)SIV
DNApresentinearlyinfectionbyCTLescapemutant(EM)strainsduringlaterinfection.Usingastrain-specificrealtimePCR
assay,wequantifiedtherelativeamountsofWTandEMstrainsinplasmaSIVRNAandcellularSIVDNA.Thuswecantrack
theformationandturnoverofSIVDNAinsortedrestingCD4+Tcells.WestudiedserialplasmaandPBMCsamplesfrom20
SIV-infectedMane-A*10positivepigtailmacaquesthathaveasignatureGagCTLescapemutation.Inanimalswithlowviral
load,WTviruslaiddownearlyininfectionisextremelystable,andthedecayofthisWTspeciesisveryslow,consistentwith
findingsinsubjectsonanti-retroviralmedications.However,duringactive,highlevelinfection,mostSIVDNAinrestingcells
was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results
suggestthat,inordertoreducetheformationofastablepopulationofSIVDNA,itwillbeimportanteithertointervenevery
earlyorinterveneduringactivereplication.
Citation: Reece J, Petravic J, Balamurali M, Loh L, Gooneratne S, et al. (2012) An ‘‘Escape Clock’’ for Estimating the Turnover of SIV DNA in Resting CD4+ T
Cells.PLoSPathog8(4):e1002615.doi:10.1371/journal.ppat.1002615
Editor:GuidoSilvestri,EmoryUniversity,UnitedStatesofAmeric
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