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Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4.

Abstract : HIV-1 envelope glycoproteins (Env), expressed at the cell surface, induce apoptosis of uninfected CD4+ T cells, contributing to the development of AIDS. Here we demonstrate that, independently of HIV replication, transfected or HIV-infected cells that express Env induced autophagy and accumulation of Beclin 1 in uninfected CD4+ T lymphocytes via CXCR4. The same phenomena occurred in a T cell line and in transfected HEK.293 cells that expressed both wild-type CXCR4 and a truncated form of CD4 that is unable to bind the lymphocyte-specific protein kinase Lck. Env-mediated autophagy is required to trigger CD4+ T cell apoptosis since blockade of autophagy at different steps, by either drugs (3-methyladenine and bafilomycin A1) or siRNAs specific for Beclin 1/Atg6 and Atg7 genes, totally inhibited the apoptotic process. Furthermore, CD4+ T cells still underwent Env-mediated cell death with autophagic features when apoptosis was inhibited. These results suggest that HIV-infected cells can induce autophagy in bystander CD4+ T lymphocytes through contact of Env with CXCR4, leading to apoptotic cell death, a mechanism most likely contributing to immunodeficiency.
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https://www.hal.inserm.fr/inserm-00156834
Contributor : Patrice Codogno <>
Submitted on : Monday, June 25, 2007 - 1:22:27 PM
Last modification on : Wednesday, September 16, 2020 - 5:05:42 PM
Long-term archiving on: : Thursday, April 8, 2010 - 9:17:29 PM

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Lucile Espert, Mélanie Denizot, Marina Grimaldi, Véronique Robert-Hebmann, Bernard Gay, et al.. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4.. Journal of Clinical Investigation, American Society for Clinical Investigation, 2006, 116 (8), pp.2161-72. ⟨10.1172/JCI26185⟩. ⟨inserm-00156834⟩

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