PATHOGENESIS OF LENTIVIRUS NEUROLOGIC DISEASE

神经系统疾病现在被认为是一种毁灭性的， 人类免疫缺陷病毒（HIV）的常见后果 感染 病毒进入神经系统的途径， 病毒损伤的机制尚不清楚。 实用模型 慢病毒引起的神经系统疾病的研究将具有重要价值 在这些问题的研究中。 猫嗜T淋巴细胞慢病毒 （FTLV）是一种新描述的猫慢病毒， 免疫抑制，T淋巴细胞，并根据 下述初步数据似乎是神经毒性的。 本提案的目的是：（1）进一步界定 神经毒力，2）确定外周细胞和组织 复制FTLV和病毒传播到 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 通过分析猫的组织，从各级神经 系统，从皮层到外周神经，在以下时间间隔 颅内或外周病毒接种。 的程度和 病毒复制的分布将使用 兔抗病毒抗体原位免疫细胞化学 与核酸探针杂交。 参与细胞 将确定炎症反应，并确定 感染的炎症和神经细胞测定。 的 髓磷脂的完整性以及 将研究髓鞘形成中的任何缺陷。 病毒复制将 在体外在相关的天然原代细胞系中进行研究 主持人 该病毒将被克隆，以提供足够的分子 用于病毒定位和确定病毒状态的探针 神经系统内的病毒基因表达，并最终 允许研究基因组结构基因表达， 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.