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效果 抗原刺激对 SIV 发病机制和病毒进展的影响 加载到SIV/恒河猴模型系统中。 在一项实验中， 感染SIV的恒河猴小剂量肌注免疫 细菌超抗原导致血浆病毒含量增加 5-50 倍 免疫后两周通过 QC-PCR 测定的 RNA 水平 与未免疫、感染 SIV 的对照相比。 在第二个实验中， 一系列百白破疫苗免疫后出现 SIV 感染 导致六只接受治疗的恒河猴中有五只疾病迅速进展 猕猴，尽管针对 SIV 产生了体液免疫反应。 预免疫动物疾病快速进展的频率很高 与未免疫人群中观察到的频率 (10/31) 有显着差异 和类似的 siv 感染，历史对照（p=0.030；Fisher 精确 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 数据分析表明 病毒清除的初始速率，而不是峰值水平或最终水平 病毒载量的平台水平，与疾病相关（或预测） 课程。 其他实验正在进行中以确认和完善 这些观察结果。