Ability to induce p53 and caspase-mediated apoptosis in primary CD4+ T cells is variable among primary isolates of human immunodeficiency virus type 1

Satoshi Komoto, Masanobu Kinomoto, Haruko Horikoshi, Miki Shiraga, Takeshi Kurosu, Tetsu Mukai, Wattana Auwanit, Toru Otake, Isao Oishi, Kazuyoshi Ikuta

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)435-446
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume18
Issue number6
DOIs
Publication statusPublished - 01-01-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology
  • Infectious Diseases

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