Chinnaiyan A M, Woffendin C, Dixit V M, Nabel G J
Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0602, USA.
Nat Med. 1997 Mar;3(3):333-7. doi: 10.1038/nm0397-333.
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.
加速程序性细胞死亡，即细胞凋亡，是导致人类免疫缺陷病毒（HIV）感染所特有的CD4 + T细胞耗竭的原因之一。因此，有人提出限制细胞凋亡可能是一种治疗HIV感染的方法。然而，我们发现，暴露于HIV-1的T白血病细胞或外周血单核细胞（PBMC）在细胞死亡抑制剂N-苄氧羰基-Val-Ala-Asp-氟甲基酮（z-AVD-fmk）存在的情况下，病毒复制增强。此外，靶向促凋亡白介素-1β转换酶（ICE）样蛋白酶的z-VAD-fmk刺激了来自HIV-1感染无症状个体的活化PBMC中的内源性病毒产生。这些发现表明，程序性细胞死亡可能是限制HIV传播的有益宿主机制，而抑制它的策略可能对受感染宿主产生有害后果。
