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Cell Host Microbe. 2015 Oct 14;18(4):463-70. doi: 10.1016/j.chom.2015.09.010.

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

Author information

1
School of Public Health, Division of Infectious Diseases and Virology, University of California, Berkeley, Berkeley, CA 94720, USA; Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA.
2
Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA.
3
Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: wgreene@gladstone.ucsf.edu.

Abstract

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.

PMID:
26468749
PMCID:
PMC4627664
DOI:
10.1016/j.chom.2015.09.010
[Indexed for MEDLINE]
Free PMC Article

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