Dynamic Correlation between Intrahost HIV-1 Quasispecies Evolution and Disease Progression 英文参考文献.docVIP

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Dynamic Correlation between Intrahost HIV-1 Quasispecies Evolution and Disease Progression 英文参考文献.doc

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Dynamic Correlation between Intrahost HIV-1 Quasispecies Evolution and Disease Progression 英文参考文献

DynamicCorrelationbetweenIntrahostHIV-1 QuasispeciesEvolutionandDiseaseProgression HaYounLee1,2*,AlanS.Perelson2,Su-ChanPark3,ThomasLeitner2 1Department of Biostatistics and Computational Biology, University of Rochester Medical Center, New York, United States of America, 2Theoretical Biology and Biophysics,LosAlamosNationalLaboratory,LosAlamos,NewMexico,UnitedStatesofAmerica,3InstituteofTheoreticalPhysics,CologneUniversity,Ko¨ln,Germany Abstract Quantifying the dynamics of intrahost HIV-1 sequence evolution is one means of uncovering information about the interactionbetweenHIV-1andthehostimmunesystem.Inthechronicphaseofinfection,commondynamicsofsequence divergenceanddiversityhavebeenreported.WedevelopedanHIV-1sequenceevolutionmodelthatsimulatedtheeffects ofmutationandfitnessof sequencevariants.Theamountofevolutionwasdescribed by thedistancefromthefounder strain,andfitnesswasdescribedbythenumberofoffspringaparentsequenceproduces.Analysisofthemodelsuggested thatthepreviouslyobservedsaturationofdivergenceanddecreaseofdiversityinlaterstagesofinfectioncanbeexplained byadecreaseintheproportionofoffspringthataremutantsasthedistancefromthefounderstrainincreasesratherthan due to an increase of viral fitness. The prediction of the model was examined by performing phylogenetic analysis to estimatethechangeintherateofevolutionduringinfection.Inagreementwithourmodeling,in13outof15patients (followedfor3–12years)wefoundthattherateofintrahostHIV-1evolutionwasnotconstantbutrathersloweddownata ratecorrelatedwiththerateofCD4+T-celldecline.Thecorrelationbetweenthedynamicsoftheevolutionaryrateandthe rateofCD4+T-celldecline,coupledwithourHIV-1sequenceevolutionmodel,explainspreviouslyconflictingobservations oftherelationshipsbetweentherateofHIV-1quasispeciesevolutionanddiseaseprogression. Citation:LeeHY,PerelsonAS,ParkS-C,LeitnerT(2008)DynamicCorrelationbetweenIntrahostHIV-1QuasispeciesEvolution andDiseaseProgression.PLoS ComputBiol4(12):e1000240.doi:10.1371/journal.pcbi