Neuropathology and Tissue Culture Core

这项建议寻求继续为神经病理学和组织培养核心中心提供资金，以协助整个计划项目拨款，以评估HIV-1相关性痴呆和进行性多灶性白质脑病(PML)的发病机制，以及HIV-1和JC病毒相互作用的合作分子机制。我们将提供神经病理学专业知识，用于评估患有HIV-1脑病的艾滋病和非艾滋病PML患者的手术和尸检脑组织样本，并提供对照组织，以补充项目1、2和3中进行的分子研究。我们将根据个别项目的需要提供高纯度的小胶质细胞、少突胶质细胞和人胎中枢神经系统星形胶质细胞的培养。培养物将接受质量控制测试，以确保在项目中统一分布。我们将为所有三个项目提供已建立的永久细胞系的培养，包括祖细胞CG-4细胞和来自Pur-Alpha基因敲除小鼠的小鼠胚胎成纤维细胞。我们还将提供按需培养原代细胞或建立大鼠和转基因小鼠的细胞系。拟议的核心服务将为三个参与项目提供基本和统一的材料，以帮助他们研究HIV-1和JCV与宿主细胞因子的相互作用，并将有助于我们了解这两种中枢神经系统疾病的发病机制。

This proposal seeks continued funding of the Neuropathology and Tissue Culture Core to assist the overall program project grant in evaluating the pathogenesis of HIV-1-associated dementia and Progressive Multifocal Leukoencephalopathy (PML) and the cooperative molecular mechanisms through which HIV-1 and JC virus interact. We will provide neuropathological expertise fore the evaluation of surgical and autopsy brain tissue samples from AIDS and non-AIDS PML patients with HIV-1 encephalopathy and control tissue to complement molecular studies performed in Projects 1,2, and 3. We will provide highly purified cultures of microglia, oligodendrocytes, and astrocytes from human fetal CNS tissue as needed for the individual projects. The cultures will undergo quality control testing to ensure uniform distribution across the projects. We will provide cultures of established permanent cell lines, including the progenitor CG-4 cells and mouse embryo fibroblasts from Pur-alpha knockout mice as a service to all three projects. We will also offer on demand culturing of primary cells or establishment of cell lines from rats and genetically modified mice. The proposed Core services will provide essential and uniform material to the three participant projects to assist in their studies on the molecular biology of HIV-1 and JCV interaction with host cellular factors and will contribute to our understanding of the pathogenesis of these two CNS disorders.