Brenneman D E, Westbrook G L, Fitzgerald S P, Ennist D L, Elkins K L, Ruff M R, Pert C B
Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Nature. 1988 Oct 13;335(6191):639-42. doi: 10.1038/335639a0.
The clinical manifestations of AIDS (acquired immune deficiency syndrome) often include neuropsychiatric and neurological deficits, including early memory loss and progressive dementia. HIV (human immunodeficiency virus), the aetiological agent of AIDS, is probably carried by infected macrophages in the central nervous system. The virus enters cells by binding its envelope glycoprotein gp120 to the CD4 antigen present on brain and immune cells. From the data reported in this paper, we now suggest that the neuronal deficits associated with HIV may not be entirely a result of infectivity, but that gp120 shed from HIV could directly produce the neuropathology as a result of its interference with endogenous neurotrophic substances. It is known that an analogue of a sequence contained in vasoactive intestinal peptide (VIP) occurs in all known sequenced gp120 isolates and that VIP is important for neuronal survival in cell culture. Here we show that purified gp120 from two diverse HIV isolates and a recombinant gp120 from a third isolate were all potent in specifically producing significant neuronal cell death in dissociated hippocampal cultures derived from fetal mice, and that this could be reduced by monoclonal antibodies against the murine CD4 antigen and completely antagonized by VIP.
获得性免疫缺陷综合征（AIDS）的临床表现通常包括神经精神和神经功能缺损，其中包括早期记忆力丧失和进行性痴呆。艾滋病的病原体——人类免疫缺陷病毒（HIV），可能由中枢神经系统中受感染的巨噬细胞携带。该病毒通过其包膜糖蛋白gp120与脑和免疫细胞上存在的CD4抗原结合而进入细胞。根据本文报道的数据，我们现在认为与HIV相关的神经元缺损可能并非完全是感染性的结果，而是HIV脱落的gp120可能因其干扰内源性神经营养物质而直接导致神经病理学变化。已知在所有已知测序的gp120分离株中都存在血管活性肠肽（VIP）所含序列的类似物，并且VIP在细胞培养中对神经元存活很重要。在此我们表明，来自两种不同HIV分离株的纯化gp120以及来自第三种分离株的重组gp120在特异性诱导源自胎鼠的离体海马培养物中显著的神经元细胞死亡方面均具有强效作用，并且这一作用可被抗小鼠CD4抗原的单克隆抗体减弱，并被VIP完全拮抗。
