title: 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.
abstract: Apoptosis and syncytium formation are two mechanisms by which human immunodeficiency virus type 1 (HIV-1) impairs uninfected CD4+ T-cell function and are mainly involved in the progression of the disease to AIDS. Previously, we showed that gp120-containing, protease-deficient HIV-1 (L-2) particles generated syncytia by particle-mediated fusion with 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 blood mononuclear cells (PBMC-Ts). Activation of PBMC-Ts with phytohemagglutinin, concanavalin A, or ionomycin after incubation with L-2 particles resulted in the loss of proliferative capacity and gradual induction of apoptosis over 3 days. Wild-type strain LAI particles or recombinant gp120 were markedly less efficient (< or = 15%) at inducing such apoptosis. Western blot (immunoblot) analysis revealed that L-2 particles contained a larger amount of Env gp120 than LAI particles. Either preincubation of PBMC-Ts with a Fas antagonist or preincubation of L-2 particles with soluble CD4 blocked most of the apoptosis. This suggests that L-2-like particles can play a major role in HIV-1-induced apoptosis of uninfected bystander cells.
authors.affiliation: Section of Serology, Hokkaido University, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kameoka
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: Y H
authors.initials: YH
authors.lastname: Zheng
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
authors.forename: R B
authors.initials: RB
authors.lastname: Luftig
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology*; D014771:Virion
chemical_list: D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins