PERIPHERAL NEUROPATHY IN SIV-INFECTED CD8-DEPLETED RHESUS MACAQUES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 周围神经功能的症状性异常是HIV-1感染最常见的并发症之一，与HIV-SN一样。目前还没有有效的治疗HIV-SN的方法，也很少有HIV-SN的动物模型可以测试候选治疗药物。将使用CD8+T淋巴细胞耗尽SIV感染恒河猴的模型，这种模型具有高度的重复性，导致快速的疾病和一致的病理。鉴于CD8+T淋巴细胞耗竭SIV感染模型与HIV诱导的CNS疾病非常相似，并且SIV脑炎(SIVE)的发生率很高(~85%)，我们假设PNS病变也是高频发生的，从而为研究HIV-SN疾病的发病机制提供了一个模型。主要目的是利用CD8+T淋巴细胞耗竭SIV感染猕猴模型来确定巨噬细胞激活、单核细胞转运和病毒驱动外周神经系统(PNS)疾病的作用。本项目的具体目的是利用CD8+T淋巴细胞耗尽的SIV感染恒河猴，确定驻留巨噬细胞激活、单核细胞渗透和病毒在HIV诱导的PNS损伤中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Symptomatic abnormalities of peripheral nerve function are among the most common complications of HIV-1 infection as HIV-sensory neuropathy (HIV-SN). There are presently no effective therapies for HIV-SN, and there are few animal models of HIV-SN in which candidate therapeutic agents can be tested. The CD8+ T lymphocyte depleted SIV-infected rhesus model, which is highly reproducible and results in rapid disease with consistent pathology will be used. Given that the CD8+ T lymphocyte depletion SIV infection model has close similarities to HIV-induced CNS disease and a high incidence of SIV encephalitis (SIVE) (~85%), we hypothesize that PNS lesions also develop at a high frequency, thus providing a model for the study of the mechanisms of HIV-SN disease. The main goal is to use the CD8+ T lymphocyte depletion SIV infection macaque model to determine the role of macrophage activation, monocyte traffic and virus driving peripheral nervous system (PNS) disease. The specific aim for this project is to define the role of resident macrophage activation, monocyte infiltration and virus in the development of HIV-induced PNS injury using CD8+ T lymphocyte depleted SIV infected rhesus macaques.