title: Cell-surface-expressed HIV-1 envelope induces the death of CD4 T cells during GP41-mediated hemifusion-like events.
abstract: Cells expressing the HIV-1 envelope glycoprotein complex (gp120/gp41, Env) induce the death of target cells either after cell-to-cell fusion or after cell-to-cell contact in a fusion-independent fashion. Here, we demonstrate that Env-induced death of single cells (including primary CD4 T cells) required gp120 and gp41 function. The gp41 peptide C34, which blocked syncytium formation, completely inhibited the death of single target cells by specifically acting on gp41 function. Moreover, Env-induced single cell death was exclusively observed in CD4 cells and was associated with specific gp41-mediated transfer of lipids from the membrane of Env-expressing cells to the target cell but not with detectable cytoplasm mixing (complete fusion). We conclude that after gp120 function, gp41 mediates close cell-to-cell contacts, thereby triggering cell death in single uninfected cells in the absence of detectable cell-to-cell fusion.
authors.affiliation: Laboratori de Retrovirologia, Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Catalonia, Spain. jblanco@ns.hugtip.scs.es
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Jordi
authors.initials: J
authors.lastname: Barretina
authors.forename: Karine F
authors.initials: KF
authors.lastname: Ferri
authors.forename: Etienne
authors.initials: E
authors.lastname: Jacotot
authors.forename: Arantxa
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Armand-Ugón
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cabrera
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D016923:Cell Death; D002459:Cell Fusion; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000502:physiology*; D015497:HIV-1 / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41