[PDF][PDF] Blood-derived CD4 T cells naturally resist pyroptosis during abortive HIV-1 infection

I Muñoz-Arias, G Doitsh, Z Yang, S Sowinski… - Cell host & …, 2015 - cell.com
I Muñoz-Arias, G Doitsh, Z Yang, S Sowinski, D Ruelas, WC Greene
Cell host & microbe, 2015cell.com
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 …
Summary
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.
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