Adamson D C, Wildemann B, Sasaki M, Glass J D, McArthur J C, Christov V I, Dawson T M, Dawson V L
Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Pathology 2-210, Baltimore, MD 21287, USA.
Science. 1996 Dec 13;274(5294):1917-21. doi: 10.1126/science.274.5294.1917.
Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-type 1 (HIV-1) infection. Proinflammatory molecules such as tumor necrosis factor alpha and eicosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of neuronal injury, because cytokines may activate the immunologic (type II) isoform of NO synthase (iNOS). The levels of iNOS in severe HIV-1-associated dementia coincided with increased expression of the HIV-1 coat protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-dependent mechanism. Thus, gp41-induced NO formation may contribute to the severe cognitive dysfunction associated with HIV-1 infection.
间接机制与1型人类免疫缺陷病毒（HIV-1）感染相关的痴呆症发病机制有关。肿瘤坏死因子α和类花生酸等促炎分子在HIV-1相关痴呆症患者的中枢神经系统中升高。一氧化氮（NO）是神经元损伤的潜在介质，因为细胞因子可能激活NO合酶（iNOS）的免疫（II型）同工型。严重HIV-1相关痴呆症中iNOS的水平与HIV-1包膜蛋白gp41表达增加一致。此外，gp41在大鼠神经元和神经胶质细胞混合原代培养物中诱导iNOS，并通过NO依赖机制杀死神经元。因此，gp41诱导的NO形成可能导致与HIV-1感染相关的严重认知功能障碍。
