T Cell Apoptosis in HIV Infection: Mechanisms and Relevance for AIDS Pathogenesis

Abstract

Human immunodeficiency virus (HIV) infection results in the progressive destruction of CD4 T lymphocytes, generally associated with disease progression. Despite years of investigation, the mechanisms responsible for the deletion of this lymphocyte subset are still not elucidated (Levy 1993; Weiss 1993; Gougeon 1995). CD4 cell destruction can be mediated directly by virus replication as a consequence of viral gene expression or indirectly by priming of uninfected cells to apoptosis when triggered by different agents. For example, Tat, a viral transcription factor, was shown to affect transciption of genes involved in cell survival. Tat was found to upregulate Bcl-2 expression, protecting cells from apoptosis (Zauli et al. 1995). In contrast, establishment of stable Tat-expressing cell lines or addition of exogenous Tat have been reported to sensitize cells to CD95-, anti-T-cell receptor (TCR)- and anti-CD4-induced apoptosis (Li et al. 1995; Westendorp et al. 1995). Vpr gene, required for productive infection of non-dividing cells (Hattori et al. 1990), was also recently found to induce apoptosis by blocking the cell cycle in the G2 phase (Bartz et al. 1996; Steward et al. 1997). The cytopathic effect of HIV in CD4 T cell cultures, manifested by ballooning of cells and formation of syncytia, was shown to be associated with apoptosis (Laurent-Crawford et al. 1991; Terai et al. 1991).