Differential Role of Autophagy in CD4 T Cells and Macrophages during X4 and R5 HIV-1 Infection 英文参考文献.docVIP

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Differential Role of Autophagy in CD4 T Cells and Macrophages during X4 and R5 HIV-1 Infection 英文参考文献.doc

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Differential Role of Autophagy in CD4 T Cells and Macrophages during X4 and R5 HIV-1 Infection 英文参考文献

DifferentialRoleofAutophagyinCD4TCellsand MacrophagesduringX4andR5HIV-1Infection LucileEspert1.,MihaylVarbanov1.,Ve′roniqueRobert-Hebmann1,SophieSagnier1,IanRobbins2, Franc?oiseSanchez1,VirginieLafont1,MartineBiard-Piechaczyk1* 1CPBS,UM1,UM2,CNRS,InstitutdeBiologie,4,CS69033,Montpellier,France,2Institutdege′ne′tiqueMole′culaire,Montpellier,France Abstract Background: HIV-1 can infect and replicate in both CD4 T cells and macrophages. In these cell types, HIV-1 entry is mediatedbythebindingofenvelopeglycoproteins(gp120andgp41,Env)tothereceptorCD4andacoreceptor,principally CCR5orCXCR4,dependingon theviralstrain(R5 orX4,respectively).UninfectedCD4Tcells undergoX4Env-mediated autophagy,leadingtotheirapoptosis,amechanismnowrecognizedascentraltoimmunodeficiency. Methodology/PrincipalFindings:Wedemonstrateherethatautophagyandcelldeatharealsoinducedintheuninfected CD4 T cells by HIV-1 R5 Env, while autophagy is inhibited in productively X4 or R5-infected CD4 T cells. In contrast, uninfected macrophages, a preserved cell population during HIV-1 infection, do not undergo X4 or R5 Env-mediated autophagy.Autophagosomes,however,arepresentinmacrophagesexposedtoinfectiousHIV-1particles,independentlyof coreceptor use. Interestingly, we observed two populations of autophagic cells: one highly autophagic and the other weaklyautophagic.Surprisingly,virusescouldbedetectedintheweaklyautophagiccellsbutnotinthehighlyautophagic cells.Inaddition,weshowthatthetriggeringofautophagyinmacrophagesisnecessaryforviralreplicationbutadditionof BafilomycinA1,whichblocksthefinalstagesofautophagy,stronglyincreasesproductiveinfection. Conclusions/Significance: Taken together, our data suggest that autophagy plays a complex, but essential, role in HIV pathologybyregulatingbothviralreplicationandthefateofthetargetcells. Citation:EspertL,VarbanovM,Robert-HebmannV,SagnierS,RobbinsI,etal.(2009)DifferentialRoleofAutophagyinCD4TCellsandMacrophagesduringX4 andR5HIV-1Infection.PLoSONE4(6):e5787.doi:10.13