GENETICS OF NEUROPATHOGENIC SIV INFECTION

神经病性 SIV 感染的遗传学

• 批准号: 7958317
• 负责人: Shawn Patrick O'Neil
• 金额: $ 6.23万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958317
• 关键词: AIDS Dementia Complex; Affect; Blood - brain barrier anatomy; Blood Circulation; Brain; Computer Retrieval of Information on Scientific Projects Database; Encephalitis; Funding; Grant; HIV; HIV Infections; HIV Seropositivity; HIV encephalitis; Immune response; Immunity; Immunologic Surveillance; Individual; Institution; Macaca; Modeling; Monkeys; Neuraxis; Neurologic; New England; Pathogenesis; Play; Primates; Research; Research Personnel; Resources; Role; SIV; SIV encephalitis; Source; Staging; United States National Institutes of Health; Viral; Virus Diseases; base; monocyte; nonhuman primate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV-associated dementia is a progressive neurological condition that affects a significant proportion of HIV-infected people, and occurs as a result of viral replication in the brain. HIV enters the brain (neuroinvasion) by the transmigration of infected blood monocytes across the blood-brain barrier during normal immune surveillance of the central nervous system. Although HIV-infected monocytes can probably be found in the circulation of all seropositive individuals, not all HIV-positive people develop HIV encephalitis (HIVE) or HIV-associated dementia. This suggests that viral determinants or host immunity play an important role in determining whether HIV infection becomes established in the brain. We have developed a nonhuman primate model of HIVE that uses an isolate (SIVsmmFGb) of simian immunodeficiency virus (SIV) that is highly neuropathogenic in pigtailed macaque monkeys. Dr. Novembre is using this model at the Yerkes Center to investigate the influence of viral determinants on neuroinvasion and the pathogenesis of SIVE, while we are using this model to investigate the impact of the innate and adaptive immune responses on the earliest stages of SIV encephalitis (SIVE).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 艾滋病毒相关性痴呆是一种进行性神经系统疾病，影响了相当一部分艾滋病毒感染者，并因病毒在大脑中复制而发生。 在中枢神经系统的正常免疫监视期间，HIV通过受感染的血液单核细胞穿过血脑屏障的迁移进入大脑（神经侵入）。 虽然HIV感染的单核细胞可能在所有血清阳性个体的循环中发现，但并非所有HIV阳性者都会发展为HIV脑炎（HIVE）或HIV相关性痴呆。 这表明，病毒决定因素或宿主免疫力在决定HIV感染是否在大脑中建立起重要作用。 我们已经开发了一个非人灵长类动物模型的HIVE，使用分离（SIVsmmFGb）的猿猴免疫缺陷病毒（SIV），这是高度神经致病性的猪尾猕猴。 Novembre博士正在Yerkes中心使用该模型研究病毒决定因素对神经侵袭和SIVE发病机制的影响，而我们正在使用该模型研究先天性和适应性免疫反应对SIV脑炎（SIVE）早期阶段的影响。