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

L Espert, M Denizot, M Grimaldi… - The Journal of …, 2006 - Am Soc Clin Investig
L Espert, M Denizot, M Grimaldi, V Robert-Hebmann, B Gay, M Varbanov, P Codogno
The Journal of clinical investigation, 2006Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation