MEMBRANE EXPRESSION OF HIV ENVELOPE GLYCOPROTEINS TRIGGERS APOPTOSIS IN CD4 CELLS

The cytopathic effect of HIV-1 and HIV-2 in CD4+ lymphocytes has been shown to be associated with apoptosis or programmed cell death. Using different experimental conditions, we demonstrate here that apoptosis is triggered by cell membrane expression of the mature HIV envelope gl ycoproteins, gp120-gp41 complex, and their interaction with CD4 recept or molecules. Viral entry alone did not induce apoptosis but virus rep lication was required in order to produce the gp120-gp41 complex. Inde ed, expression of the HIV env gene alone in the CD4+ T cell line (CEM) was sufficient for the induction of apoptosis. In general, syncytium formation and apoptosis induction were closely associated as both even ts require functional envelope glycoproteins and CD4 molecules. Nevert heless, apoptosis but not syncytium formation was suppressed by a mono clonal antibody against CD4 that does not affect gp120 binding. Furthe rmore, single-cell killing by apoptosis was observed in infected cell cultures treated with a monoclonal antibody against gp41, which comple tely abolishes the formation of syncytia. These results indicate that apoptosis is not the consequence of toxic effects induced by the forma tion of syncytia but is triggered by the HIV envelope glycoproteins. T herefore, cell death during HIV infection in CD4+ lymphocyte cultures is due to a specific event triggered by the gp120-gp41 heterodimer com plex programming death in metabolically active cells.