NEUROPATHOGENESIS IN AIDS

艾滋病的神经发病机制

• 批准号: 3901017
• 负责人: R ANAND
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3901017
• 关键词: AIDS; antiAIDS agent; antiviral agents; human immunodeficiency virus 1; human subject; human tissue; leukocyte activation disorder; nervous system infection; neurotropic virus; pentosan; transfection; viral myelinopathy; virus cytopathogenic effect; virus genetics; virus replication; zidovudine

A. Neuroviraology. The pathogenesis of human immunodeficiency virus (HIV)-induced encephaopathy is being studies by using two approaches. Firstly, by understanding the interaction of HIV-1 isolates, in general, with the neural tissues. Secondly, by detailed biological and molecular characterization of HIV-1 variants isolated from persons with neurological deficiencies, especially in the absence of overt immune suppression. The second approach is expected to elucidate if certain strains of HIV-1 are uniquely neuropathic. The virus-cell interaction studies have shown that human neural cell lines can be transfected with HIV DNA resulting in transient virus replication. Currently, our preliminary findings using primary rodent brain cultures reveal that HIV can partially replicate in these cells upon direct infection, and is specifically cytopathic to neural cells. We have biologically and molecularly characterized one of HIV-1 isolates (HIV-br) and have observed the presence of a 39-base duplication of nucleotides in the nef gene. B. Antiviral Agents. We have investigated the anti-HIV activity of sodium pentosan polysulfate (PPS), a sulfated sugar compound, normal human peripheral mononuclear cells (PMNC). PPS has potent anti-HIV activity, shows profound anti-HIV synergism with AZT, is essentially nontoxic to PMNC and has lymphoproliferative effect in culture.

答：神经病毒学。人类免疫缺陷病毒的致病机制 目前正在使用两种方法研究艾滋病毒引起的脑病。 首先，通过了解HIV-1分离株之间的相互作用，总的来说， 与神经组织的关系。其次，通过详细的生物学和分子生物学研究 神经科患者HIV-1变异株的特性研究 缺陷，特别是在没有明显的免疫抑制的情况下。这个 第二种方法预计将阐明某些HIV-1毒株是否 独一无二的神经病。病毒与细胞相互作用的研究表明， 人类神经细胞系可被感染HIV DNA，导致 短暂的病毒复制。目前，我们的初步发现是使用 啮齿动物大脑原代培养显示艾滋病毒可以在 这些细胞直接感染，并对神经产生特异性的细胞病变 细胞。我们有一种生物学和分子特征的HIV-1 分离株(HIV-br)，并观察到存在39个碱基的重复 在nef基因中的核苷酸。 B.抗病毒药物。我们研究了钠的抗HIV活性。 聚硫酸戊聚糖(PPS)，一种硫酸盐糖类化合物，正常人 外周血单个核细胞(PMNC)。PPS具有很强的抗HIV活性， 与AZT显示出深刻的抗HIV协同作用，对PMNC基本无毒 并在培养中具有淋巴增殖作用。