PROTEASE-DEFECTIVE, GP120-CONTAINING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES INDUCE APOPTOSIS MORE EFFICIENTLY THAN DOES WILD-TYPE VIRUS OR RECOMBINANT GP120 PROTEIN IN HEALTHY DONOR-DERIVED PERIPHERAL-BLOOD T-CELLS

Apoptosis and syncytium formation are two mechanisms by which human im munodeficiency virus type 1 (HIV-1) impairs uninfected CD4(+) T-cell f unction and are mainly involved in the progression of the disease to A IDS, Previously, we showed that gp120-containing, protease-deficient H IV-1 (L-2) particles generated syncytia by particle-mediated fusion wi th uninfected cultured CD4(+) T cells, Here, we present evidence that such L-2 particles can induce apoptosis in 40 to 50% of T cells which were enriched from HIV-1-negative healthy donor-derived peripheral blo od mononuclear cells (PBMC-Ts), Activation of PBMC-Ts with phytohemagg lutinin, concanavalin A, or ionomycin after incubation with L-2 partic les resulted in the loss of proliferative capacity and gradual inducti on of apoptosis over 3 days, Wild-type strain LAI particles or recombi nant gp120 were markedly less efficient (less than or equal to 15%) at inducing such apoptosis, Western blot (immunoblot) analysis revealed that L-2 particles contained a larger amount of Env gp120 than LAI par ticles, Either preincubation of PBMC-Ts with a Fas antagonist or prein cubation of L-2 particles with soluble CD4 blocked most of the apoptos is. This suggests that L-2-like particles can play a major role in HIV -1-induced apoptosis of uninfected bystander cells.