%0 Journal Article
%T DRAM Triggers Lysosomal Membrane Permeabilization and Cell Death in CD4+ T Cells Infected with HIV
%A Mireille Laforge
%A Sophie Limou
%A Francis Harper
%A Nicoletta Casartelli
%A Vasco Rodrigues
%A Ricardo Silvestre
%A Houda Haloui
%A Jean-Francois Zagury
%A Anna Senik
%A Jerome Estaquier
%J PLOS Pathogens
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1003328
%X 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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003328