Kanmogne Georgette D, Kennedy R C, Grammas Paula
Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City 73104, USA.
J Neuropathol Exp Neurol. 2002 Nov;61(11):992-1000. doi: 10.1093/jnen/61.11.992.
Breakdown of the blood-brain barrier is commonly seen in patients with human immunodeficiency virus (HIV)-associated dementia, despite the lack of productive HIV-infection of the brain endothelium. Through this damaged blood-brain barrier, HIV and HIV-infected monocytes/macrophages infiltrate the brain and further infect microglia and brain macrophages. Neuronal cell death and dysfunction are the underlying cause of HIV-associated dementia, but no productive HIV-infection of neurons has been documented. It is likely that secreted viral products play a major role in blood-brain barrier damage and neuronal cell death. The aim of the present study was to examine the effect of HIV-1 gp160 peptides and gp120 proteins on brain microvascular endothelial cells and neurons from both human and rats. Four of the 7 gp160 peptides tested evoked significant neurotoxicity. Two different full-length recombinant HIV gp120 proteins (HIV-1CM235 gp120 and HIV-1MN gp120) also induced neuronal and brain endothelial cell death, and concentrations as little as 1 ng/ml evoked pronounced morphological changes in these cells and marked cytotoxicity. This study suggests that HIV proteins and peptides that are shed in vivo may be directly involved in blood-brain barrier damage and neuronal cell death in HIV-associated dementia.
尽管脑内皮细胞不存在活跃的HIV感染，但血脑屏障破坏在人类免疫缺陷病毒（HIV）相关痴呆患者中很常见。通过这种受损的血脑屏障，HIV及被HIV感染的单核细胞/巨噬细胞侵入大脑，进而感染小胶质细胞和脑巨噬细胞。神经元细胞死亡和功能障碍是HIV相关痴呆的根本原因，但尚未有文献记载神经元存在活跃的HIV感染。分泌的病毒产物可能在血脑屏障损伤和神经元细胞死亡中起主要作用。本研究的目的是检测HIV-1 gp160肽段和gp120蛋白对人和大鼠脑微血管内皮细胞及神经元的影响。所检测的7种gp160肽段中有4种引起了显著的神经毒性。两种不同的全长重组HIV gp120蛋白（HIV-1CM235 gp120和HIV-1MN gp120）也诱导了神经元和脑内皮细胞死亡，低至1 ng/ml的浓度就能引起这些细胞明显的形态变化和显著的细胞毒性。本研究提示，体内释放的HIV蛋白和肽段可能直接参与了HIV相关痴呆中的血脑屏障损伤和神经元细胞死亡。
