PATHOGENESIS OF LENTIVIRUS NEUROLOGIC DISEASE

神经系统疾病现在被认为是一种毁灭性的和 人类免疫缺陷病毒(HIV)的常见后果 感染。病毒进入神经系统和 病毒损害的机制尚不清楚。一个实用的模型 慢病毒诱导的神经系统疾病的研究将具有重要价值 在对这些问题的研究中。猫T淋巴细胞慢病毒 猫慢病毒(FTLV)是一种新发现的猫慢病毒 免疫抑制，T淋巴营养，并在此基础上 下面描述的初步数据似乎是神经毒性的。 这项建议的目的是：(1)进一步界定 神经毒力，2)测定外周细胞和组织 复制FTLV和将病毒传播到 神经系统，以及3)病毒的分子特征 及其在相关细胞和组织中的表达。 病毒引起的神经损伤的性质和程度将是 通过分析猫的所有水平的神经组织进行研究 系统，从皮质到周围神经，间隔时间如下 接种颅内或外周病毒。范围和 病毒复制的分布将使用以下方法确定 兔抗病毒抗体免疫细胞化学及原位观察 与核酸探针杂交。参与该事件的细胞 将确定炎症反应，并确定 确定感染的炎性细胞和神经细胞。这个 髓鞘的整体性及其结构和生化性质 任何髓鞘形成的缺陷都将被研究。病毒复制将 在相关的天然原代细胞系中进行体外研究 主持人。病毒将被克隆，以提供足够的分子 病毒定位和状态判定的探针法 病毒基因在神经系统内的表达，并最终导致 允许研究基因组结构基因表达和 对FTLV的监管。

Neurologic disease is now recognized to be a devastating and frequent consequence of human immunodeficiency virus (HIV) infection. The means of viral entry into the nervous system and the mechanisms of viral damage are unknown. A practical model of lentivirus induced neuorlogical disease would be of great value in the study of these questions. Feline T lymphotropic lentivirus (FTLV) is a newly described feline lentivirus which is immunosuppressive, T lymphotrophic, and on the basis of preliminary data described below appears to be neurovirulent. The aims of this proposal are: (1) to further define the neurovirulence, 2) to determine the peripheral cells and tissue replicating FTLV and the means of spread of the virus to the nervous system, and 3) the molecular characterization of the virus and its expression in relevant cells and tissues. The nature and extent of viral induced neural damage will be studied by analysis of feline tissues from all levels of the nervous systems, from cortex to peripheral nerve, at intervals following intracranial or peripheral virus inoculation. The extent and distribution of viral replication will be determined using immunocytochemistry with rabbit antiviral antibody and in situ hybridization with nucleic acid probes. The cells involved in the inflammatory response will be identified, and the identity of infected inflammatory and neural cells determined. The intergrity of myelin and the structural and biochemical nature of any defects in myelination will be studied. Viral replication will be studied in vitro in relevant primary cell lines of the natural host. The virus will be cloned to provide adequate molecular probes for virus localization and determination of the state of viral gene expression within the nervous system, and ultimately to allow study of the genomic structure gene expression and regulation of FTLV.