AIDS PATHOGENESIS - THE ROLE OF ACCESSORY GENE-MUTATIONS, LEADING TO FORMATION OF LONG-LIVED PERSISTENTLY INFECTED-CELLS AND OR APOPTOSIS-INDUCING HIV-1 PARTICLES/

Human immunodeficiency virus type 1 (HIV-1) infection indirectly induc es activation-dependent apoptosis in bystander immune CD4(+) T-cells, a hallmark of AIDS pathogenesis. It is well known that this pathogenet ic event is significantly correlated with a high virus load. Active vi ral replication occurs in HIV-1 asymptomatic carriers throughout all s tages of clinical disease. Most of the HIV-1 in plasma is derived from short-lived infected cells with a half life of a few days; however, a minor population of virus is derived from long-lived persistently and latently infected cells. Recently, the importance of such latent rese rvoirs for HIV-1 has come to the forefront because of studies with pot ent antiretroviral inhibitors that block only new rounds of infection. An initial large drop in viral load occurs within two weeks as noted by a decrease in plasma viremia. This is then followed by a slower sec ond-phase decay, since only a small fraction of latently infected rest ing CD4(+) T-cells carry replication-competent, integrated provirus. T his review highlights the mechanisms of apoptosis induction in bystand er immune cells by both protease-defective, gp120-containing HIV-1 par ticles, as well as by wild-type virus that appears to be derived predo minantly from long-lived infected cells. A model involving the NH2-ter minal Nef domain (p7) in this 'bystander apoptosis' event is also pres ented. (C) 1997 Elsevier Science B.V.