Vignoli A L, Martini I, Haglid K G, Silvestroni L, Augusti-Tocco G, Biagioni S
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Rome, Italy.
Mol Cell Biochem. 2000 Dec;215(1-2):73-80. doi: 10.1023/a:1026590916661.
Neurological impairment is a common feature of Acquired Immunodeficiency Syndrome (AIDS); functional alterations have been reported both in central and peripheral nervous system and the Human Immunodeficiency Virus (HIV) envelope glycoprotein gp120 has been proposed as a neurotoxin acting through a calcium-dependent mechanism. On the other hand it has been reported that gp120 treatment also induce about a 20% decrease in the cerebral glucose utilization and in the cellular ATP levels. The reported observations were performed on experimental system where also non-neuronal cells where present; in order to evaluate whether a direct interaction between HIV proteins and neuronal cells takes place, we used a neuroblastoma cultures where only neuronal cells are present. We analysed the effects of gp120 on the N18TG2 neuroblastoma clone. Treatments were performed both on growing and confluent cultures. Short time treatment with gp120 of confluent cultures causes a 25% reduction in the level of neuron-specific enolase, resulting in a similar decrease of oxygen consumption. Long time exposure of growing cells also causes a reduction in cell survival. Furthermore, using a membrane-specific fluorescent probe we observed that gp120 produces an increase of membrane trafficking. These observations suggest a direct interaction between the viral envelope protein and neuronal cells, which results in an alteration of glycolytic metabolism. This alteration may be related to the neurologic impairments observed in AIDS patients.
神经功能障碍是获得性免疫缺陷综合征（AIDS）的常见特征；中枢和外周神经系统均有功能改变的报道，有人提出人类免疫缺陷病毒（HIV）包膜糖蛋白gp120是一种通过钙依赖机制起作用的神经毒素。另一方面，有报道称，用gp120处理也会使脑葡萄糖利用和细胞ATP水平降低约20%。这些报道的观察结果是在存在非神经元细胞的实验系统上进行的；为了评估HIV蛋白与神经元细胞之间是否发生直接相互作用，我们使用了仅存在神经元细胞的神经母细胞瘤培养物。我们分析了gp120对N18TG2神经母细胞瘤克隆的影响。在生长的和汇合的培养物上都进行了处理。用gp120对汇合培养物进行短时间处理会导致神经元特异性烯醇化酶水平降低25%，从而使耗氧量出现类似程度的下降。对生长中的细胞进行长时间暴露也会导致细胞存活率降低。此外，使用膜特异性荧光探针，我们观察到gp120会使膜转运增加。这些观察结果表明病毒包膜蛋白与神经元细胞之间存在直接相互作用，这会导致糖酵解代谢发生改变。这种改变可能与艾滋病患者所观察到的神经功能障碍有关。
