The Fiery Side of HIV–Induced T Cell Death

Science  24 Jan 2014:
Vol. 343, Issue 6169, pp. 383-384
DOI: 10.1126/science.1250175

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In untreated HIV-1 infection, the progressive destruction of CD4 T cells gives rise to a devastating number of opportunistic infections—the hallmark of AIDS. Yet, it remains unclear how HIV-1 inexorably depletes these essential immune cells. Most of the dying CD4 T cells are uninfected “bystanders” that self-destruct upon exposure to HIV-1 DNA products generated during aborted infection (1). Doitsh et al. (2) and a report by Monroe et al. on page 428 in this issue (3) show that these truncated fragments of HIV-1 DNA trigger CD4 T cell demise through an intense inflammatory cell death pathway—called pyroptosis—after their recognition by an intracellular DNA sensor (4, 5).