GENETICS OF NEUROPATHOGENIC SIV INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 艾滋病毒相关痴呆是一种进行性神经疾病，影响相当大比例的艾滋病毒感染者，并由于病毒在大脑中复制而发生。在中枢神经系统的正常免疫监测过程中，艾滋病毒通过感染的单核细胞跨越血脑屏障进入大脑(神经侵袭)。虽然感染艾滋病毒的单核细胞很可能在所有血清阳性者的循环中都能找到，但并不是所有艾滋病毒阳性的人都会患上艾滋病毒脑炎(HIVE)或艾滋病毒相关痴呆。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确立方面发挥了重要作用。我们已经开发了一个非人类的灵长类蜂箱模型，它使用了一种猴免疫缺陷病毒(SIV)的分离株(SIVsmmFGb)，这种病毒对辫尾猕猴具有高度的神经致病性。Novembre博士正在耶克斯中心使用这个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，同时我们正在使用这个模型来研究先天和获得性免疫反应对SIV脑炎(SIVE)早期阶段的影响。

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).