Cell-surface-expressed HIV-1 envelope induces the death of CD4 T cells during GP41-mediated hemifusion-like events.
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.
Blanco
Julià
J
Laboratori de Retrovirologia, Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Catalonia, Spain. jblanco@ns.hugtip.scs.es
Barretina
Jordi
J
Ferri
Karine F
KF
Jacotot
Etienne
E
Gutiérrez
Arantxa
A
Armand-Ugón
Mercedes
M
Cabrera
Cecilia
C
Kroemer
Guido
G
Clotet
Bonaventura
B
Esté
José A
JA
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
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41