NEUROCYTOPATHIC EFFECT OF DIFFERENT ISOLATES OF HIV-1

HIV-1 不同分离株的神经细胞病变作用

• 批准号: 3811265
• 负责人: R ANAND
• 金额: --
• 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/3811265
• 关键词: AIDS; AIDS dementia complex; cell type; human immunodeficiency virus 1; laboratory rat; medical complication; organ culture; polymerase chain reaction; virus DNA; virus RNA; virus cytopathogenic effect; virus morphology; virus protein; virus receptors; virus virus interaction

The precise mechanisms of the neuropathogenesis of HIV-1 infection are unknown. We examined the interaction between HIV-1 and rat cerebellar cells (RCC) to determine whether the virus may be directly cytopathic to neural cells. Primary cultures of RCC were derived from 8-day-old rat cerebella and grown in a chemically defined medium in presence or absence of cytosine arabinoside (AraC, 10 micro-M). Two HIV-1 isolates (HIV-1,br and NA-4) were from AIDS patients with, and the other two (HIV-1,bru or LAV and HIV-1,451) were from patients without overt neurological symptoms. RCC were exposed for 24 h to equal virus inocula 24 h after seeding. Cell type-specific markers were assayed at indicated times post exposure. RCC cultures consisted of neurons, astrocytes, microglia, and oligodendrocytes (in order of decreasing abundance). All cell types except neurons proliferated in absence of AraC. Upon exposure to HIV-1, progressive disruption of neural network and destruction of cells were observed. The cytopathic effect increased with time and virus dose. HIV-1 specific DNA and RNA were detected by polymerase chain reaction (PCR) using multiple primers and Northern blotting, respectively. Culture supernatants occasionally contained viral proteins. HIV-1,br and NA-4 were consistently more cytopathic and infectious than HIV-1,bru and HIV-1,451. These results demonstrate that HIV-1 is cytopathic to non-dividing rat brain cells in culture, and that HIV-L,br from the brain of an AIDS dementia patient (Anand, R. et al., Virology 1989; 168:79-89) is more potent than other isolates tested. These results suggest that HIV-1 may exert a direct neurocytopathic effect in adult brain. Currently, we are characterizing the nature of the HIV-1,br associated neurocytopathic effect and confirming the infectivity. It is important to define the cell surface molecules (receptors) on neurons that interact with HIV-1, especially with isolates such as HIV-l,br.

HIV-1感染的神经发病机制的确切机制是 未知我们研究了HIV-1和大鼠小脑细胞之间的相互作用 (RCC)以确定病毒是否可能直接导致神经细胞病变 细胞原代培养的RCC来自8日龄大鼠小脑 并在存在或不存在胞嘧啶的化学成分确定的培养基中生长 阿拉伯糖苷（AraC，10 μ M）。两种HIV-1分离株（HIV-1，br和NA-4） 来自艾滋病患者，以及其他两种（HIV-1，bru或LAV和HIV-1，451） 都是没有明显神经症状的病人RCC暴露 接种后24 h，接种量与病毒接种量相等。细胞类型特异 在暴露后的指定时间测定标记物。RCC培养物 由神经元、星形胶质细胞、小胶质细胞和少突胶质细胞组成（按顺序 的减少）。除神经元外，所有细胞类型均在 没有AraC。一旦暴露于HIV-1， 观察到细胞的网络和破坏。细胞病变效应 随着时间和病毒剂量的增加。HIV-1特异性DNA和RNA， 使用多个引物通过聚合酶链反应（PCR）检测， 北方印迹法。培养上清液偶尔 含有病毒蛋白。HIV-1、br和NA-4的感染率始终高于 比HIV-1、bru和HIV-1，451更具有细胞病变性和传染性。 这些结果 证明HIV-1对未分裂的大鼠脑细胞具有细胞病变性， 培养物和HIV-L，从艾滋病痴呆患者脑中提取 （Anand，R.例如，Virology 1989; 168：79-89）比其他的更有效 测试的分离物。这些结果表明，HIV-1可能发挥直接的作用， 神经细胞病变效应。目前，我们正在描述 HIV-1，br相关神经细胞病变效应的性质，并证实 传染性确定细胞表面分子是很重要的 与HIV-1相互作用的神经元（受体），特别是与分离物 如HIV-1、br.