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The inhibition of pro-apoptotic ICE-like proteases enhances HIV replication

Nature Medicine volume 3, pages 333–337 (1997)Cite this article

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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Author notes

  1. Arul M. Chinnaiyan and Clive Woffendin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical Center, 1301 Catherine St., Ann Arbor, Michigan, 48109-0602, USA

    Arul M. Chinnaiyan & Vishva M. Dixit

  2. Howard Hughes Medical Institute and Departments of Internal Medicine and Biological Chemistry, University of Michigan Medical Center, 1150 West Medical Center Drive, 4520 MSRBI, Ann Arbor, Michigan, 48109-0650, USA

    Clive Woffendin & Gary J. Nabel

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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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