SIV MODEL FOR PEDIATRIC AIDS

儿科艾滋病的 SIV 模型

基本信息

批准号：
2320705
负责人：
RICHARD P BRADBURY
金额：
$ 21.25万
依托单位：
BIOQUAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-11-07 至 1995-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2320705
关键词：
SIV MODEL PEDIATRIC AIDS

项目摘要

SIV-infected rhesus macaques are a model for HIV infection and AIDS dementia complex in humans. This study is directed toward 1) identifying the mechanisms underlying the neuronal complications that result from viral infection of the CNS, manifested in impaired motor and/or cognitive function, and 2) testing of the tolerance and efficacy of CNS-directed antiviral agents. We are studying the sequelae of viral infection of the CNS including the neurobehavioral and neuroimmunological consequences, and examining the role of the brain as a viral reservoir and the dissemination of the virus systemically throughout the course of the disease. This animal model allows us to examine the brains of SIV-infected animals at various stages of disease both with and without CNS impairments at the time of death. We have found an increase in astrogliosis in cortical gray matter of neurologically impaired animals, a correlation in the elevation of the endogenous neurotoxin quinolinic acid with onset of motor impairment, and a correlation of elevated somatostatin mRNA in frontal cortex of animals with impairments in both motor and cognitive function. Testing of the tolerance and efficacy of AZT in rhesus neonates, as a model for perinatal transmission of HIV, has revealed that infusion of this anitviral during and for six months following inoculation results in prolonged survival, a decrease in the systemic and CNS viral burden, and a delay in motor impairments compared to untreated animals.

感染 SIV 的恒河猴是 HIV 感染和艾滋病的模型人类痴呆症。这项研究的目的是 1) 确定引起神经元并发症的机制中枢神经系统病毒感染，表现为运动和/或认知受损功能，以及2）测试中枢神经系统导向的耐受性和功效抗病毒剂。我们正在研究病毒感染的后遗症中枢神经系统（CNS），包括神经行为和神经免疫学后果，以及检查大脑作为病毒储存库和传播的作用在整个疾病过程中系统地感染病毒。这动物模型使我们能够检查感染 SIV 的动物的大脑疾病的各个阶段，无论是否有中枢神经系统损伤死亡时间。我们发现皮质灰质中星形胶质细胞增多神经受损动物的问题，海拔的相关性内源性神经毒素喹啉酸与运动开始的关系损伤，以及额叶生长抑素 mRNA 升高的相关性运动和认知功能均受损的动物的皮质。测试 AZT 在恒河猴新生儿中的耐受性和有效性，作为一种围产期艾滋病毒传播模型显示，输注这种抗病毒药物在接种期间和接种后六个月内会导致延长生存期，减少全身和中枢神经系统病毒负荷，以及与未经治疗的动物相比，运动损伤延迟。