Apoptosis of uninfected cells induced by HIV envelope glycoproteins.
Apoptosis, or programmed cell death, is a key event in biologic homeostasis but is also involved in the pathogenesis of many human diseases including human immunodeficiency virus (HIV) infection. Although multiple mechanisms contribute to the gradual T cell decline that occurs in HIV-infected patients, programmed cell death of uninfected bystander T lymphocytes, including CD4+ and CD8+ T cells, is an important event leading to immunodeficiency. The HIV envelope glycoproteins (Env) play a crucial role in transducing this apoptotic signal after binding to its receptors, the CD4 molecule and a coreceptor, essentially CCR5 and CXCR4. Depending on Env presentation, the receptor involved and the complexity of target cell contact, apoptosis induction is related to death receptor and/or mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated cell death leading to T cell depletion and clinical complications and covers the sometimes conflicting studies that address the possible mechanisms of T cell death.
Ahr
Barbara
B
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR 5121-UM1, Institut de Biologie, 4, Bd Henri IV, CS 89508, 34960 Montpellier Cedex 2, France. barbara.ahr@univ-montp1.fr
Robert-Hebmann
Véronique
V
Devaux
Christian
C
Biard-Piechaczyk
Martine
M
D017209:Apoptosis / Q000187:drug effects*; D015686:Gene Products, env / Q000494:pharmacology*; D006678:HIV; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes / Q000473:pathology
D015686:Gene Products, env