Infection of CD4+ T cells with human immunodeficiency virus (HIV) can result in a caspase-independent cell-death pathway, but the details of this process remain unclear. In PLoS Pathogens, Estaquier and colleagues link the autophagy-regulatory protein DRAM to HIV-triggered death of CD4+ T cells. Infection of T cells with HIV induces DRAM expression in a manner dependent on the tumor suppressor p53 and subsequent activation of autophagy and cell death. However, autophagy is not critical for cell death; instead, after infection with HIV, DRAM associates with lysosomes and initiates destabilization of their membranes—a classic cell-intrinsic death initiator. How DRAM actually disrupts lysosomal membranes is unclear, but the cell death that results from DRAM activity substantially impairs viral infection. DRAM-mediated killing may therefore represent a cell-intrinsic mechanism for eliminating virus-infected cells.

PLoS Pathog. (2 May 2013) doi:10.1371/journal.ppat.1003328