Cellular Tropism & Reservoir in Brain with HIV-Clade C

描述（由申请人提供）：对感染hiv - B支病毒的人群的研究表明，患者通常会发展为具有重要社会经济后果的痴呆性疾病。然而，世界上最常见的艾滋病毒感染是艾滋病毒进化支C，关于其神经系统表现的信息很少。两个进化支之间的一个重要区别是，hiv进化支C几乎完全是趋化因子受体CCR5的。由于CCR5表达细胞主要存在于中枢神经系统的小胶质细胞中，在星形胶质细胞、神经元和内皮细胞中也有少量表达，因此确定该病毒在hiv - C进化支系感染患者大脑中的细胞趋向性是很重要的。感染HIV进化支C的人群机会性感染发生率高，这通常是HIV感染的表现。另一个尚未解决的重要问题是，在中枢神经系统机会性感染的过程中，HIV感染的细胞是否会侵入大脑？由于构成炎症浸润的细胞类型可能因各种机会性感染而不同，因此确定哪些患者在机会性感染治疗后患艾滋病毒脑炎的风险更大也很重要。研究艾滋病毒C支感染的神经病理学后果的一个主要障碍是，在感染该病毒的地区和人群中缺乏神经学、神经放射学或神经病理学服务。印度班加罗尔的国家心理健康和神经科学研究所是独一无二的，因为该研究所提供上述所有服务，并拥有一个成熟的脑库。这个脑库的独特之处在于尸检时间很短，大多数情况下只有2-8小时。因此，我们建议在现有设施的基础上，建立免疫组织病理学、原位杂交、RT-PCR和前病毒DNA定量检测脑组织HIV的方法来解决上述问题。我们相信，这将成为几个项目发展的焦点，以解决艾滋病毒感染的神经发病机制，并为治疗方法和疫苗开发制定合理的设计。

DESCRIPTION (provided by applicant): Studies from populations infected with HIV-clade B virus suggest that patients often develop a dementing illness with important socioeconomic consequences. However, the most common HIV infection worldwide is with HIV-clade C and very little information is available with regards to its neurological manifestations. An important difference between the two clades is that HIV-clade C is nearly exclusively chemokine receptor CCR5 tropic. Since CCR5 expressing cells are present in the central nervous system predominantly in microglia and to a lesser degree in astrocytes, neurons and endothelial cells, it is important to determine the cellular tropism of this virus in brain of HIV-clade C infected patients. Populations infected with HIV-clade C have a high incidence of opportunistic infections and this is often the presenting manifestation of HIV infection. Another important question that remains unanswered is that do HIV infected cells invade the brain during the course of a CNS opportunistic infection? Since the types of cells that make up the inflammatory infiltrates may be different for the various opportunistic infections, it is also important to determine which patients may be at a greater risk for developing HIV encephalitis following treatment of the opportunistic infections. A major obstacle to studying the neuropathological consequences of HIV-clade C infection has been the lack of neurological, neuroradiological or neuropathological services available in areas and populations infected with this virus. The National Institute of Mental Health and Neurosciences in Bangalore, India is unique because all the above services are available at this institute and it has an established brain bank. A unique feature if this brain bank is it has short autopsy times, of 2-8 hours in most cases. Hence, we propose to augment the existing facilities, establish assays for detection and quantification of HIV in brain tissue by immunohistopathology, in situ hybridization, RT-PCR and quantitation of proviral DNA to address the above questions. We believe this will serve as a nidus for the development of several projects to address the neuropathogenesis of HIV infection and develop a rational design for therapeutic approaches and vaccine development.