MOLECULAR VIROLOGICAL STUDIES OF AIDS CNS DISORDERS

艾滋病中枢神经系统疾病的分子病毒学研究

• 批准号: 3410715
• 负责人: IRVIN S.Y. CHEN
• 金额: $ 12.07万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3410715
• 关键词: AIDS; cellular pathology; central nervous system disorders; encephalitis; gene expression; genetic manipulation; genome; human immunodeficiency virus; human subject; human tissue; molecular cloning; molecular pathology; nervous system infection; nucleic acid hybridization; nucleic acid sequence; pathology; postmortem; tissue /cell culture; virus DNA; virus antigen; virus classification; virus genetics; virus infection mechanism; virus replication

Acquired immunodeficiency syndrome (AIDS) includes a broad spectrum of clinical disorders including the recent description of central nervous system (CNS) disorders. It has been the experience of many medical centers that about 75-80% of patients with AIDS show pathologic abnormalities of the CNS. Many of these patients show no signs of other pathogens, and these cases, known as AIDS-related subacute encephalopathy, are correlated with the presence of AIDS virus in CNS tissue at autopsy. Increasingly, the earliest signs of AIDS can be detected as disorders which include dementia, spinal cord degeneration, peripheral neuropathy, hearing loss, visual loss, and other neurologic symptoms. Therefore, it is of importance to understand HIV infection in the CNS, and how this infection leads to pathologic processes resulting in CNS disorders. Recent studies by other groups have directly demonstrated the presence of human immunodeficiency virus (HIV, HTLV-III, LAV, ARV) in the CNS, including cerebrospinal fluid (CSF) and brain tissue samples. In initial studies, we have isolated genetically and biologically distinct viruses from cerebrospinal fluid and brain tissue samples of the same individual. These viruses have been characterized by gross restriction endonuclease analysis and ability to replicate in vitro in various glial and hematopoietic cell types. In the proposed studies, we will investigate these viruses further by mapping the biological phenotypes to specific genes of the viral genome. In addition, we will extend such analyses to other isolates of AIDS virus made from other individuals.

获得性免疫缺陷综合征（艾滋病）包括广泛的 临床疾病谱，包括最近描述的 中枢神经系统（CNS）病症。 它一直是 根据许多医疗中心的经验，大约75-80%的 AIDS患者表现出CNS的病理异常。 这些患者中的许多人没有表现出其他病原体的迹象， 这些病例被称为艾滋病相关亚急性脑病， 与中枢神经系统组织中艾滋病病毒的存在相关， 尸检 越来越多的艾滋病的早期症状可以被发现 包括痴呆，脊髓退化， 周围神经病变、听力损失、视力丧失和其他 神经系统症状 因此， 了解CNS中的HIV感染，以及这种感染如何导致 导致CNS疾病的病理过程。 其他研究小组最近的研究直接表明， 人类免疫缺陷病毒（HIV，HTLV-III，LAV， 中枢神经系统（包括脑脊液（CSF）和大脑）中的ARV 组织样本 在最初的研究中，我们从基因上分离出了 生物学上不同于脑脊液和脑的病毒 同一个人的组织样本 这些病毒已经 其特征在于总限制性内切酶分析， 在各种胶质细胞和造血细胞中体外复制能力 类型 在拟议的研究中，我们将调查这些病毒 进一步通过将生物表型映射到 病毒基因组 此外，我们将把这种分析扩展到 从其他人身上分离出的艾滋病病毒。