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Cell-to-cell transmission of HIV-1 is required to trigger pyroptotic death of lymphoid tissue-derived CD4 T cells
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Details:
  • Pubmed ID:
    26321639
  • Pubmed Central ID:
    PMC4565731
  • Description:
    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.

  • Document Type:
  • Collection(s):
  • Funding:
    1DP1036502/DP/NCCDPHP CDC HHS/United States
    DP1 DA036502/DA/NIDA NIH HHS/United States
    P30 AI027763/AI/NIAID NIH HHS/United States
    P30 AI027763/AI/NIAID NIH HHS/United States
    R01 AI078783/AI/NIAID NIH HHS/United States
    R21 AI102782/AI/NIAID NIH HHS/United States
    R21 AI102782/AI/NIAID NIH HHS/United States
    R56 AI118453/AI/NIAID NIH HHS/United States
    U19 AI096113/AI/NIAID NIH HHS/United States
    U19 AI096113/AI/NIAID NIH HHS/United States
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