Journal
CELL REPORTS
Volume 12, Issue 10, Pages 1555-1563Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.08.011
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Funding
- NIH/NIAID [R21 AI102782, 1DP1036502, U19 AI096113]
- UCSF/Robert John Sabo Trust Award
- A.P. Giannini Foundation Postdoctoral Research Fellowship
- NIH (UCSF-GIVI Center for AIDS Research) [P30 AI027763]
- Gladstone Flow Cytometry Core
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The progressive depletion of CD4 T cells underlies clinical progression to AIDS in untreated HIV-infected subjects. Most dying CD4 T cells correspond to resting nonpermissive cells residing in lymphoid tissues. Death is due to an innate immune response against the incomplete cytosolic viral DNA intermediates accumulating in these cells. The viral DNA is detected by the IFI16 sensor, leading to inflammasome assembly, caspase-1 activation, and the induction of pyroptosis, a highly inflammatory form of programmed cell death. We now show that cell-to-cell transmission of HIV is obligatorily required for activation of this death pathway. Cell-free HIV-1 virions, even when added in large quantities, fail to activate pyroptosis. These findings underscore the infected CD4 T cells as the major killing units promoting progression to AIDS and highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.
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