CAML Does Not Modulate Tetherin-Mediated Restriction of HIV-1 Particle Release 英文参考文献.docVIP

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CAML Does Not Modulate Tetherin-Mediated Restriction of HIV-1 Particle Release 英文参考文献.doc

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CAML Does Not Modulate Tetherin-Mediated Restriction of HIV-1 Particle Release 英文参考文献

CAMLDoesNotModulateTetherin-MediatedRestriction ofHIV-1ParticleRelease MohammedS.Ali¤,JasonHammonds,LingmeiDing,PaulSpearman* DepartmentofPediatrics,EmoryUniversityandChildren’sHealthcareofAtlanta,Atlanta,Georgia,UnitedStatesofAmerica Abstract Background:Tetherin/BST-2isarecently-identifiedpotentrestrictionfactorinhumancellsthatrestrictsHIVparticlerelease followingparticleformationandbuddingattheplasmamembrane.Vpucounteractstetherin’srestrictionofparticlerelease inamannerthathasnotyetbeenfullydefined.Werecentlyidentifiedcalcium-modulatingcyclophilinligand(CAML)asa Vpu-interacting protein that also restricts particle release. We hypothesized that CAML may act to enhance tetherin- mediated restriction of particle release and thereby explain how two distinct factors could be responsible for Vpu- responsiverestriction. Methodology/PrincipalFindings:Endogenouslevelsoftetherininhumancellscorrelatedwellwiththeirrestrictionpattern andresponsivenesstoVpu,whilelevelsofcellularCAMLproteindidnot.TetherinbutnotCAMLwasinduciblebyinterferon inawidevarietyofhumancells.StabledepletionofhumanCAMLinrestrictiveHeLacellshadnoeffectoncellsurfacelevels of tetherin, and failed to relieve tetherin-mediated restriction. Stable depletion of tetherin from HeLa cells, in contrast, rendered HeLa cells permissive and Vpu-unresponsive. Tetherin but not CAML expression in permissive human cells renderedthemrestrictiveandVpuresponsive.DepletionofCAMLhadnoinfluenceoncellsurfacelevelsoftetherin. Conclusions/Significance: We conclude that tetherin restricts particle release and does not require CAML for this effect. Furthermore,theseresultsdonotsupportamajorroleforCAMLinrestrictingHIVparticlereleaseinhumancells. Citation: AliMS, Hammonds J,Ding L, Spearman P (2010) CAMLDoes NotModulate Tetherin-Mediated Restriction of HIV-1 ParticleRelease.PLoSONE 5(2): e9005.doi:10.1371/journal.pone.0009005 Editor:DouglasF.Nixon,UniversityofCaliforniaSanFrancisco,UnitedStatesofAmerica ReceivedJanuary7,2010;AcceptedJ