HIV and CXCR4 in a kiss of autophagic death
Beth Levine, Donald L. Sodora
Beth Levine, Donald L. Sodora
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2078-2080. https://doi.org/10.1172/JCI29447.
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Commentary

HIV and CXCR4 in a kiss of autophagic death

Abstract

AIDS is characterized by CD4+ T lymphocyte depletion, yet the mechanisms underlying this central aspect of HIV pathogenesis are still poorly understood. In this issue of the JCI, Espert et al. identify a mechanism by which the HIV envelope glycoprotein can induce death in uninfected CD4+ T cells (see the related article beginning on page 2161). The HIV envelope glycoprotein interacts with CXC chemokine receptor 4 to activate the lysosomal degradation pathway of autophagy, which is necessary for both apoptotic and nonapoptotic cell death.

Authors

Beth Levine, Donald L. Sodora

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Figure 1

Model depicting events following binding of natural and viral ligands to the CXCR4 chemokine receptor.

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Model depicting events following binding of natural and viral ligands to...
(A) Binding of the natural ligand SDF-1 to CXCR4 induces lymphocyte homing and functions in lymphocyte development (reviewed in ref. 17). (B) Binding of the HIV envelope glycoprotein (Env) to CXCR4 activates cellular autophagy, which then leads to both apoptotic and autophagic cell death. Autophagy activation and both forms of cell death are blocked by (a) a small molecule inhibitor of HIV entry via the CXCR4 receptor, AMD3100; (b) the pharmacological inhibitor of autophagy, 3-MA; and (c) siRNA directed against 2 autophagy genes, beclin 1 and atg7 (see ref. 4). The mechanism by which the different binding events at the same receptor in A and B result in distinct cellular outcomes is not known.