Blood-Derived CD4 T Cells Naturally Resist Pyroptosis During Abortive HIV-1 Infection

Details

• Alternative Title:
  Cell Host Microbe
• Personal Author:
  Muñoz-Arias, Isa ; Doitsh, Gilad ; Yang, Zhiyuan ; Sowinski, Stefanie ; Ruelas, Debbie ; Greene, Warner C.
• 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.
• Subjects:
  Article CD4-Positive T-Lymphocytes Cells, Cultured Coculture Techniques Gene Expression HIV-1 Humans NF-kappa B Nuclear Proteins Phosphoproteins Pyroptosis Real-Time Polymerase Chain Reaction

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• Source:
  Cell Host Microbe. 18(4):463-470.
• Pubmed ID:
  26468749
• Pubmed Central ID:
  PMC4627664
• Document Type:
  Journal Article
• 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
• Volume:
  18
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:eb596fcd577b633e78a6e66c6dc237c9807479260ff5b3924f5d512efa35e9ea
• Download URL:
  https://stacks.cdc.gov/view/cdc/37419/cdc_37419_DS1.pdf
• File Type:
  [PDF - 906.25 KB ]