MOLECULAR BIOLOGY OF HUMAN VIRUS INFECTIONS, HIV-1 AND JCV

人类病毒感染、HIV-1 和 JCV 的分子生物学

• 批准号: 3881680
• 负责人: E O MAJOR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 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/3881680
• 关键词: DNA binding protein; DNA replication origin; Polyomavirus hominis 2; astrocytes; gene expression; genetic enhancer element; genetic manipulation; genetic promoter element; genetic transcription; human T cell lymphotropic virus type 1; human immunodeficiency virus 1; human tissue; in situ hybridization; nervous system infection; neurotropic virus; nucleic acid probes; oligodendroglia; progressive multifocal leukoencephalopathy; simian virus 40; tissue /cell culture; transposon /insertion element; virus DNA; virus classification; virus diseases; virus genetics; virus infection mechanism; virus protein

Progressive multifocal leucoencephalopathy (PML) and AIDS encephalopathy are viral induced neurological diseases which occur almost exclusively in individuals whose immune systems are impaired. We have investigated the molecular pathogenesis of these diseases by developing laboratory assays that examine the human polyomavirus, JCV, and the human immunodeficiency virus, HIV-1, the causes of PML and AIDS encephalopathy, respectively. We have developed a new methodology that prepares brain biopsy tissue for in situ DNA hybridization to detect viral genomes on the same day of surgery. For example, in brain biopsy tissue from an AIDS patient with PML, JCV DNA can be detected using a non-radioactive, nucleic acid probe. Data from this rapid molecular diagnostic assay facilities patient management decisions on a more timely basis. We have also examined protein interactions between JCV and infected glial cells. The non-structural JCV T protein can bind the cellular retinoblastoma protein which normally functions for growth regulation. Results from this study suggest that the oncogenic properties of JCV may be related to viral proteins interfering with normal cellular metabolism. Other human viruses have been studied for their association with glial cells of the nervous system. Astroglial cells from human fetal brain respond very rapidly to the introduction of the HIV-1 genome. AIDS virus proteins are synthesized within hours of transfection. However, HIV-1 infection of astrocytes results in a persistent infection without cytopathic effects. Varicella-zoster virus, the agent which causes shingles, can productively infect Schwann cells, the myelinating cell of the peripheral nervous system. VZV proteins are also produced very rapidly following infection and are efficiently assembled into progeny virions.

进行性多灶性白质脑病（PML）和艾滋病脑病 是病毒引起的神经系统疾病，几乎只发生在 免疫系统受损的人。我们已经调查了 这些疾病的分子发病机制，通过发展实验室分析 检测人类多瘤病毒JCV和人类免疫缺陷病毒 病毒，HIV-1，PML和艾滋病脑病的原因，分别。 我们 已经开发出一种新的方法， 在手术当天进行原位DNA杂交以检测病毒基因组。 例如，在患有PML的AIDS患者的脑活检组织中，JCV DNA 可以使用非放射性核酸探针检测。数据从 这种快速的分子诊断测定便于患者管理， 更及时地做出决定。我们还检测了蛋白质 JCV和受感染的神经胶质细胞之间的相互作用。 非结构性JCV T蛋白可以结合细胞视网膜母细胞瘤蛋白， 生长调节功能。这项研究的结果表明， JCV的致癌特性可能与病毒蛋白干扰 正常的细胞代谢。其他人类病毒已经被研究过， 它们与神经系统胶质细胞的联系。星形胶质细胞 从人类胎儿的大脑反应非常迅速，以介绍 HIV-1基因组。艾滋病病毒蛋白在感染后数小时内 转染然而，星形胶质细胞的HIV-1感染导致 持续感染，无细胞病变效应。水痘-带状疱疹病毒， 引起带状疱疹的因子可以有效地感染雪旺细胞， 周围神经系统的髓鞘形成细胞。VZV蛋白是 在感染后也非常迅速地产生， 组装成后代病毒体。