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Blood-Derived CD4 T Cells Naturally Resist Pyroptosis During Abortive HIV-1 Infection
Filetype[PDF - 906.25 KB]


Details:
  • Pubmed ID:
    26468749
  • Pubmed Central ID:
    PMC4627664
  • Funding:
    T32 AI007620/AI/NIAID NIH HHS/United States
    1DP1036502/DP/NCCDPHP CDC HHS/United States
    S10 RR028962/RR/NCRR NIH HHS/United States
    P30 AI027763/AI/NIAID NIH HHS/United States
    R21 AI102782/AI/NIAID NIH HHS/United States
    S10 RR028962-01/RR/NCRR NIH HHS/United States
    U19 AI096113/AI/NIAID NIH HHS/United States
    T32 AL007620-04/PHS HHS/United States
    R21AI102782/AI/NIAID NIH HHS/United States
    U19AI0961133/AI/NIAID NIH HHS/United States
    DP1 DA036502/DA/NIDA NIH HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    Progression to AIDS is driven by CD4 T cell depletion, mostly involving pyroptosis elicited by abortive HIV infection of CD4 T cells in lymphoid tissues. Inefficient reverse transcription in these cells leads to cytoplasmic accumulation of viral DNAs that are detected by the DNA sensor IFI16, resulting in inflammasome assembly, caspase-1 activation, and pyroptosis. Unexpectedly, we found that peripheral blood-derived CD4 T cells naturally resist pyroptosis. This resistance is partly due to their deeper resting state, resulting in fewer HIV-1 reverse transcripts and lower IFI16 expression. However, when co-cultured with lymphoid-derived cells, blood-derived CD4 T cells become sensitized to pyroptosis, likely recapitulating interactions occurring within lymphoid tissues. Sensitization correlates with higher levels of activated NF-κB, IFI16 expression, and reverse transcription. Blood-derived lymphocytes purified from co-cultures lose sensitivity to pyroptosis. These differences highlight how the lymphoid tissue microenvironment encountered by trafficking CD4 T lymphocytes dynamically shapes their biological response to HIV.