Acheampong Edward, Mukhtar Muhammad, Parveen Zahida, Ngoubilly Noel, Ahmad Navid, Patel Charvi, Pomerantz Roger J
The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferdon University, Philadelphia, Pennsylvania 19107, USA.
Virology. 2002 Dec 20;304(2):222-34. doi: 10.1006/viro.2002.1666.
Ethanol may have significant effects on human immunodeficiency virus type I (HIV-1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied on the proapoptotic potential of various HIV-1 proteins in primary isolated human brain microvascular endothelial cells (MVECs), a major cellular component of the blood-brain barrier. Low-passage primary brain MVECs were treated with recombinant HIV-1 proteins Nef, Vpr, Tat and gp120 proteins from X4, R5, and X4R5 viral strains, with and without ethanol at various relevant concentrations. The apoptotic potential of each HIV-1 protein with and without ethanol was compared with cells treated with ethanol alone or GST protein as a control, under similar conditions. Specific HIV-1 proteins induced apoptosis in primary isolated human brain MVECs, which was potentiated on treatment with 0.1 and 0.3% (v/v) ethanol. Cotreatment with ethanol and specific HIV-1 proteins showed enhanced lactate dehydrogenase release, compared with MVECs treated with ethanol alone. The presence of ethanol in in vitro culture medium also enhanced HIV-1 protein-mediated tumor necrosis factor-alpha production, compared with cells treated with ethanol alone or GST protein. Thus, these studies demonstrate ethanol's potential for inducing apoptosis of human MVECs with relevant HIV-1-specific proteins and suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and neuropathogenesis in vivo.
乙醇可能在体内对I型人类免疫缺陷病毒（HIV-1）的发病机制产生显著影响。因此，研究了乙醇处理对原代分离的人脑微血管内皮细胞（MVECs）中各种HIV-1蛋白促凋亡潜力的影响，MVECs是血脑屏障的主要细胞成分。低代原代脑MVECs用来自X4、R5和X4R5病毒株的重组HIV-1蛋白Nef、Vpr、Tat和gp120蛋白处理，处理时添加或不添加各种相关浓度的乙醇。在相似条件下，将每种添加或未添加乙醇的HIV-1蛋白的凋亡潜力与单独用乙醇或GST蛋白作为对照处理的细胞进行比较。特定的HIV-1蛋白在原代分离的人脑MVECs中诱导凋亡，在用0.1%和0.3%（v/v）乙醇处理后凋亡增强。与单独用乙醇处理的MVECs相比，乙醇与特定HIV-1蛋白共同处理显示乳酸脱氢酶释放增加。与单独用乙醇或GST蛋白处理的细胞相比，体外培养基中乙醇的存在也增强了HIV-1蛋白介导的肿瘤坏死因子-α的产生。因此，这些研究证明了乙醇与相关HIV-1特异性蛋白共同诱导人MVECs凋亡的潜力，并提示在增强HIV-1体内神经侵袭和神经发病机制方面存在潜在的协同效应。
