Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo 英文参考文献.docVIP

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Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo 英文参考文献.doc

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Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo 英文参考文献

QuantitativeDeepSequencingRevealsDynamicHIV-1 EscapeandLargePopulationShiftsduringCCR5 AntagonistTherapyInVivo AtheM.N.Tsibris1,2,BetteKorber3,4.,RamyArnaout5,6,7.,CarstenRuss7,Chien-ChiLo3 ,Thomas Leitner3,BrianGaschen3,JamesTheiler3,RogerParedes2,5,8,ZhaohuiSu9,MichaelD.Hughes9,RoyM. Gulick10,WayneGreaves11,EoinCoakley12,CharlesFlexner13,ChadNusbaum7,DanielR.Kuritzkes2,5* 1MassachusettsGeneralHospital,Boston, Massachusetts,United StatesofAmerica, 2HarvardMedicalSchool,Boston, Massachusetts,UnitedStatesofAmerica, 3Los AlamosNationalLaboratories,LosAlamos,NewMexico,UnitedStatesofAmerica,4SantaFeInstitute,SantaFe,NewMexico,UnitedStatesofAmerica,5Brighamand Women’sHospital,Boston,Massachusetts,UnitedStatesofAmerica,6ProgramforEvolutionaryDynamics,HarvardUniversity,Cambridge,Massachusetts,UnitedStatesof America,7BroadInstituteofMITandHarvard,Cambridge,Massachusetts,UnitedStatesofAmerica,8FundacionsirsiCaixaiLluitacontralaSIDA,HospitalUniversitari GermansTriasiPujol,UniversitatAuto`nomadeBarcelona,Badalona,Catalonia,Spain,9HarvardSchoolofPublicHealth,Boston,Massachusetts,UnitedStatesofAmerica, 10WeillMedicalCollege,CornellUniversity,NewYork,NewYork,UnitedStatesofAmerica,11Schering-PloughResearchInstitute,Kennilworth,NewJersey,UnitedStates of America, 12Monogram Biosciences, South San Francisco, California, United States of America, 13Johns Hopkins University, Baltimore, Maryland, United States of America Abstract High-throughputsequencingplatformsprovideanapproachfordetectingrareHIV-1variantsanddocumentingmorefully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-usingpopulationswereidentifiedinalargelyCCR5-usingpopulation.TheV3loopformsassociatedwithsubsequent viro