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

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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

Nat Med. 1997 Mar;3(3):333-7. Unique Identifier : AIDSLINE MED/97208921
Chinnaiyan AM; Woffendin C; Dixit VM; Nabel GJ; Department of Pathology, University of Michigan Medical Center, Ann; Arbor, Michigan 48109-0602, USA.

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.

Keywords: *Amino Acid Chloromethyl Ketones/PHARMACOLOGY *Apoptosis/DRUG EFFECTS *Cysteine Proteinase Inhibitors/PHARMACOLOGY *CD4-Positive T-Lymphocytes/VIROLOGY *HIV Infections *HIV-1/PHYSIOLOGY *Virus Replication/DRUG EFFECTS
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