title: Ability to induce p53 and caspase-mediated apoptosis in primary CD4+ T cells is variable among primary isolates of human immunodeficiency virus type 1.
abstract: Infection with human immunodeficiency virus type 1 (HIV-1) is associated with dramatic depletion of CD4(+) T cells, the major HIV-1-induced pathogenesis. Apoptosis has been suggested to play an important role for the T cell depletion and a number of mechanisms have been proposed for the apoptosis in T cells. Here, we compared the levels for apoptosis induction in primary peripheral blood mononuclear cells (PBMCs) among several laboratory strains and primary isolates of the HIV-1 subtypes B and E. The results showed that apoptosis in infected PBMCs, preferentially in CD4+ T cell population, became detectable around the time for virus production by flow cytometric terminal transferase dUTP nick end labeling (TUNEL) technique and staining with the nuclear dye Hoechst 33342. The abilities to induce apoptosis in PBMCs were highly variable in individual isolates. The increase of p53 protein in infected PBMCs, which was initiated before virus production, was observed in infected PBMCs and the levels of p53 protein were almost proportional to the rates of the isolates to induced apoptosis. The cells infected and cultured in the presence of Z-VAD-FMK had significantly decreased cell mortalities, indicating that activated caspases also played a significant role in the apoptosis. Thus, HIV-1-induced apoptosis in primary T cells was accompanied by the p53 protein and caspase activation at varied levels in primary isolates.
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komoto
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kinomoto
authors.forename: Haruko
authors.initials: H
authors.lastname: Horikoshi
authors.forename: Miki
authors.initials: M
authors.lastname: Shiraga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.forename: Tetsu
authors.initials: T
authors.lastname: Mukai
authors.forename: Wattana
authors.initials: W
authors.lastname: Auwanit
authors.forename: Toru
authors.initials: T
authors.lastname: Otake
authors.forename: Isao
authors.initials: I
authors.lastname: Oishi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D020169:Caspases / Q000502:physiology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008969:Molecular Sequence Data; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014779:Virus Replication
chemical_list: D016159:Tumor Suppressor Protein p53; D020169:Caspases