The inhibition of pro-apoptotic ICE-like proteases enhances HIV replication.
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.
Chinnaiyan
A M
AM
Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0602, USA.
Woffendin
C
C
Dixit
V M
VM
Nabel
G J
GJ
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D015658:HIV Infections; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects*
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone