Abstract
Accelerated programmed cell death, or apoptosis, contributes to the CD4+ T-cell depletion characteristic of infection by human immunodeficiency virus (HIV). It has therefore been proposed that limiting apoptosis may represent a therapeutic modality for HIV infection. We found, however, that T leukemia cells or peripheral blood mononuclear cells (PBMCs) exposed to HIV-1 underwent enhanced viral replication in the presence of the cell death inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk). Furthermore, z-VAD-fmk, which targets the pro-apoptotic interleukin-1β-converting enzyme (ICE)-like proteases, stimulated endogenous virus production in activated PBMCs derived from HIV-1-infected asymptomatic individuals. These findings suggest that programmed cell death may serve as a beneficial host mechanism to limit HIV spread and that strategies to inhibit it may have deleterious consequences for the infected host.
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Chinnaiyan, A., Woffendin, C., Dixit, V. et al. The inhibition of pro-apoptotic ICE-like proteases enhances HIV replication. Nat Med 3, 333–337 (1997). https://doi.org/10.1038/nm0397-333
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DOI: https://doi.org/10.1038/nm0397-333
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