NEUROPATHOGENESIS OF HIV ENCEPHALITIS

HIV 脑炎的神经发病机制

• 批准号: 2274639
• 负责人: CAROL K PETITO
• 金额: $ 21.31万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2274639
• 关键词: AIDS dementia complex; HIV infections; Rodentias; blood brain barrier; choroid plexus; disease /disorder model; encephalitis; histopathology; human tissue; immunocytochemistry; latent virus infection; neurotropic virus; pathologic process; postmortem; vascular endothelium permeability; virus protein

DESCRIPTION (Adapted from applicant's abstract): The human immunodeficiency virus (HIV) encephalitis and its clinical counterpart, AIDS dementia, are frequent in patients with the acquired immunodeficiency syndrome (AIDS) and are important causes of neurological morbidity in this illness. The virus enters the cerebrospinal fluid (CSF) during the initial stage of systemic infection, but actual brain infection is rare or absent prior to the development of AIDS. The route(s) whereby HIV enters the brain and the time and site at which this occurs remain somewhat controversial or are not known. Recent studies in our laboratory have shown that the blood-brain barrier (BBB) is permeable in brains of AIDS patients and that the choroid plexus (CPx) often is infected by HIV. Both of these findings may be important in the neuropathogenesis of HIV encephalitis. This application will examine the following hypotheses: 1. that HIV infects the CPx during the early stages of systemic infection and resides here during the period of clinical latency and 2. that the enhanced vascular permeability in the brain is responsible for, or enhances, the development of HIVE. The proposed experiments will explore the relationship between the enhanced vascular permeability and the CPx changes with each other and with the development of HIVE; the phenotypic and genotypic characteristics of virus in CPx, brain and spleen to determine whether CPx infection is a prerequisite for the subsequent development of HIVE; the effects of the BBB in facilitating the entry into the brain of circulating immune cells, including those infected with HIV; and the potential relevance of circulating viral proteins in mediating the BBB and CPx changes in AIDS. The proposed studies will be carried out in post-mortem brains from HIV- infected asymptomatic cases and from AIDS cases with normal brains or with HIVE, using techniques of immunocytochemistry, in situ hybridization and molecular biology. In addition, animal models of circulating HIV proteins will be used to investigate mechanisms of, and abnormalities related to, the enhanced vascular permeability in AIDS and immunological and functional alterations in the CPx.

描述（改编自申请人摘要）：人类 免疫缺陷病毒（HIV）脑炎及其临床对应物， 艾滋病痴呆，是常见的后天性患者 免疫缺陷综合征（艾滋病），是神经系统疾病的重要原因 这种病的发病率。病毒进入脑脊液 (CSF)在全身感染的初始阶段，但实际的大脑 在出现艾滋病之前，感染很少见或不存在。的 艾滋病毒进入大脑的途径，以及艾滋病毒进入大脑的时间和部位， 发生的事情仍然存在争议或未知。最近的研究 在我们的实验室已经表明，血脑屏障（BBB）是 在艾滋病患者的大脑中渗透，脉络丛（CPx） 经常被艾滋病毒感染。这两项发现可能对 HIV脑炎的神经发病机制。 本申请将检验以下假设：1.艾滋病毒 在全身感染的早期阶段感染CPx， 在临床潜伏期和2.增强的 大脑中的血管通透性负责或增强了 蜂巢的发展。拟议的实验将探索 血管通透性增强与CPx之间的关系 随着HIVE的发展而变化; CPx、脑和脾中病毒的基因型特征， 确定CPx感染是否是随后 HIVE的发展; BBB在促进进入中的作用 进入循环免疫细胞的大脑，包括那些感染了 HIV;以及循环病毒蛋白在 介导AIDS中的BBB和CPx变化。 拟议的研究将在艾滋病毒感染者的死后大脑中进行- 无症状感染者和大脑正常的艾滋病患者， 与HIVE，使用免疫细胞化学技术，原位 杂交和分子生物学。此外， 循环的HIV蛋白将被用来研究 与艾滋病血管通透性增强有关的异常， CPx的免疫和功能改变。