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).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 艾滋病毒相关痴呆是一种进行性神经系统疾病，影响很大一部分艾滋病毒感染者，是病毒在大脑中复制的结果。 在中枢神经系统的正常免疫监视过程中，HIV 通过受感染的血单核细胞跨血脑屏障迁移进入大脑（神经侵袭）。 尽管感染 HIV 的单核细胞可能存在于所有血清阳性个体的循环中，但并非所有 HIV 阳性者都会患 HIV 脑炎 (HIVE) 或 HIV 相关痴呆。 这表明病毒决定因素或宿主免疫在决定艾滋病毒感染是否在大脑中建立方面发挥着重要作用。 我们开发了一种非人灵长类 HIVE 模型，该模型使用猿猴免疫缺陷病毒 (SIV) 的分离株 (SIVsmmFGb)，该病毒对猪尾猕猴具有高度神经致病性。 Novembre 博士正在 Yerkes 中心使用该模型来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来研究先天性和适应性免疫反应对 SIV 脑炎早期阶段的影响（SIVE）。