DRAM Triggers Lysosomal Membrane Permeabilization and Cell Death in CD4(+) T Cells Infected with HIV

作者：Laforge Mireille^*; Limou Sophie; Harper Francis; Casartelli Nicoletta; Rodrigues Vasco; Silvestre Ricardo; Haloui Houda; Zagury Jean Francois; Senik Anna; Estaquier Jerome

来源：PLoS Pathogens, 2013, 9(5): e1003328.

DOI：10.1371/journal.ppat.1003328

Productive HIV infection of CD4(+) T cells leads to a caspase-independent cell death pathway associated with lysosomal membrane permeabilization (LMP) and cathepsin release, resulting in mitochondrial outer membrane permeabilization (MOMP). Herein, we demonstrate that HIV infection induces damage-regulated autophagy modulator (DRAM) expression in a p53-dependent manner. Knocking down the expression of DRAM and p53 genes with specific siRNAs inhibited autophagy and LMP. However, inhibition of Atg5 and Beclin genes that prevents autophagy had a minor effect on LMP and cell death. The knock down of DRAM gene inhibited cytochrome C release, MOMP and cell death. However, knocking down DRAM, we increased viral infection and production. Our study shows for the first time the involvement of DRAM in host-pathogen interactions, which may represent a mechanism of defense via the elimination of infected cells.

• 出版日期2013-5