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.
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Fehervari, Z. A DRAM-atic end for T cells. Nat Immunol 14, 698 (2013). https://doi.org/10.1038/ni.2650
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DOI: https://doi.org/10.1038/ni.2650