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

Nat Med. 1997 Mar;3(3):333-7. doi: 10.1038/nm0397-333.

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-AVD-fmk). Furthermore, z-VAD-fmk, which targets the pro-apoptotic interleukin-1 beta-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Apoptosis / drug effects*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Cysteine Proteinase Inhibitors / pharmacology*
  • HIV Infections*
  • HIV-1 / physiology*
  • Humans
  • Virus Replication / drug effects*

Substances

  • Amino Acid Chloromethyl Ketones
  • Cysteine Proteinase Inhibitors
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone