Apoptosis in AIDS

Infection with the human immunodeficiency virus type 1 (HIV-1) leads to pro gressive immunodeficiency and onset of opportunistic infections and neoplas ms. The loss of immune competence is associated with declines in both the f unctionality and the number of CD4+ lymphocytes. Multiple mechanisms have b een proposed to explain death and dysfunction of CD4+ T-cells. The mechanis ms of HIV-1-mediated cell death which are relevant in vivo are unclear at p resent. However, in vitro explorations on the cytopathic effects of HIV-1 h ave yielded a wealth of potential triggering events, and signaling and effe ctor pathways leading to apoptosis. The types of pro- and anti-apoptotic st imuli that have been associated with HIV-1 are multiple and often appear ov erlapping or even contradictory. This review focuses on the various molecul ar determinants from HIV-1 that play a role in induction of apoptosis in T- lymphocytes. Special attention is devoted to the viral genes, env, nef, tat and vpr, for which a significant body of literature on apotosis-related ef fects is available.