EFFECT OF ANTIGENIC STIMULATION ON AIDS AND SAIDS PATHOGENESIS

抗原刺激对艾滋病和艾滋病发病机制的影响

• 批准号: 3742077
• 负责人: NICHOLAS W LERCHE
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3742077
• 关键词: AIDS; Macaca mulatta; human immunodeficiency virus; pathologic process; simian AIDSs; simian immunodeficiency virus; virus replication

The objective of this series of studies is to determine the effect of antigenic stimulation on the progression of SIV pathogenesis and viral load in the SIV/rhesus macaque model system. In one experiment, intramuscular immunization of SIV infected rhesus macaques with low-dose bacterial superantigens resulted in a 5-50 fold increase in plasma viral RNA levels as determined by QC-PCR in the two weeks post-immunization compared to unimmunized, SIV infected controls. In a second experiment, SIV infection following a series of immunizations with DPT vaccine resulted in rapid disease progression in five of six treated rhesus macaques, despite development of a humoral immune response against SIV. The high frequency of rapid disease progression in pre-immunized animals differed significantly from frequency (10/31) observed among unimmunized and similarly siv infected, historical controls (p=0.030; Fisher's exact test). The results of both experiments support the hypothesis that antigenic stimulation increases viral replication and accelerates SIV disease progression. Analysis of QC-PCR data suggests that it is the initial rate of viral clearance, rather than the peak level or final plateau level of virus load, that correlates with (or predicts) disease course. Additional experiments are in progress to confirm and refine these observations.

这一系列研究的目的是确定 SIV发病机理进展的抗原刺激和病毒的进展 在SIV/Rhesus猕猴模型系统中加载。 在一个实验中， 低剂量的SIV感染恒河猕猴的肌内免疫 细菌超抗原导致血浆病毒增加5-50倍 免疫后两周中由QC-PCR确定的RNA水平 与未免疫的SIV感染对照相比。 在第二个实验中， 通过DPT疫苗进行一系列免疫接种后的SIV感染 六个治疗的恒河猴中有五个导致疾病的快速进展 猕猴，尽管发展了对SIV的体液免疫反应。 预免疫动物快速疾病进展的高频 在未免疫之间观察到的频率（10/31）显着不同 同样，SIV感染了历史控制（P = 0.030； Fisher的确切 测试）。 两个实验的结果都支持以下假设 抗原刺激增加病毒复制并加速SIV 疾病进展。 QC-PCR数据的分析表明这是 病毒清除的初始速率，而不是峰值或最终 病毒负荷的高原水平，与（或预测）疾病相关 课程。 正在进行其他实验以确认和完善 这些观察。