Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4
Lucile Espert, … , Patrice Codogno, Martine Biard-Piechaczyk
Lucile Espert, … , Patrice Codogno, Martine Biard-Piechaczyk
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2161-2172. https://doi.org/10.1172/JCI26185.
View: Text | PDF
Research Article AIDS/HIV

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.

Authors

Lucile Espert, Mélanie Denizot, Marina Grimaldi, Véronique Robert-Hebmann, Bernard Gay, Mihayl Varbanov, Patrice Codogno, Martine Biard-Piechaczyk

×

Figure 3

Autophagy is triggered by Env binding to CXCR4.

Options: View larger image (or click on image) Download as PowerPoint
Autophagy is triggered by Env binding to CXCR4. (A) A2.01/CD4.403 and HE...
(A) A2.01/CD4.403 and HEK/CD4.403/CXCR4 cells were cocultured for 3 days with cells that do or do not express Env and analyzed by TEM as indicated in Figure 2. Scale bar: 1 μm; 250 nm (indicated enlargements). (B) Target HEK/CD4.403/CXCR4 and HEK/CD4.403 cells were transfected with GFP or GFP-LC3 using the FuGENE 6 Transfection Reagent and cocultured for 3 days with effector cells with or without Env expression or treated with 1 μM Rapa. Adherent cells were then examined by epifluorescence. Data are representative of 3 independent experiments and more than 100 cells were counted by 2 investigators. Magnification shown. (C) Immunoblot analysis of Beclin 1 in A2.01/CD4.403, HEK/CD4.403/CXCR4, and HEK/CD4.403 cells cocultured with cells with or without Env expression. *P < 0.05; ***P < 0.001.