Immune stimulation may contribute to enhanced progression of SIV induced disease in rhesus macaques
Immune stimulation may contribute to enhanced progression of SIV induced disease in rhesus macaques
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DOI：
10.1111/j.1600-0684.1997.tb00050.x
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发表时间：
1997-08-01
影响因子：
0.7
通讯作者：
Ansari, AA
中科院分区：
文献类型：
--
作者：
Folks, T;Rowe, T;Ansari, AA
一些实验感染了SIV分离株(如SIVmac251)的恒河猴，不能血清转换，出现高血浆病毒血症，并迅速死亡(在6-7个月P.I.)。我们假设，如此快速的进展是这些动物在病毒攻击时的高度免疫激活和伴随的免疫抑制状态的结果。为了验证免疫激活导致慢病毒引起的疾病快速发展的假设，成年恒河猴感染了SIVmac251，并接受了每月一次的交替免疫计划，分别使用同种异体细胞、锁孔帽状血蓝蛋白和破伤风环状病毒(组I)。作为对照，一组猴子被感染了相同的病毒池和剂量，但没有免疫(组II)，一组被免疫的多抗原与组I相同，但没有感染SIV(组III)。I组(n=3)所有动物要么血清转换失败，要么SIV抗体水平很低，血浆p27抗原血症升高，并在8个月内死亡(2/3在4个月内死亡)。在Li组(n=8)动物中，出现了两种模式，正如我们之前注意到的那样。其中一个亚组(3只动物)表现出与I组相同的特征(未能完全血清转换，p27水平高，8个月后死亡)，而另一亚组(5只动物)血清转换，血浆p27水平低，并存活超过II个月(2/5仍存活超过22个月)。III组3只动物均保持健康。本文提供的数据表明，无论是实验的还是自然的(由于目前尚不清楚的因素)免疫刺激都可能导致慢病毒诱导的疾病加速进展，很可能是由于免疫抑制，这对于理解人类HIV-1感染的疾病进展速度的机制具有重要意义。
A number of rhesus macaques experimentally infected with SIV isolates such as SIVmac251, fail to seroconvert, develop high plasma viremia and die rapidly (within 6-7 months p.i.). We hypothesized that such rapid progression is a result of a state of hyperimmune activation and concomitant immune suppression of these animals at the time of virus challenge. In efforts to test the hypothesis that immune activation leads to rapid progression of lentivirus-induced disease, adult rhesus macaques were infected with SIVmac251 and received an alternate monthly schedule of repeated immunization with allogeneic cells, keyhole limpet hemocyanin and tetanus toroid (group I). For purposes of controls, a group of monkeys was infected with the same pool and dose of virus but were not immunized (group II) and a group was immunized with the same schedule of multiple antigens as group I but were not infected with SIV (group III). All the animals in group I (n=3) either failed to seroconvert or developed very low levels of SIV antibodies, had high plasma p27 defined antigenemia, and died within 8 months (2/3 died within 4 months). Of the animals in group LI (n=8), two patterns emerged as we had noted before. One subgroup (3 animals), displayed the same profile as group I (failure to fully seroconvert, high p27 levels and death by 8 months), whereas the other subgroup (5 animals) seroconverted, had low plasma p27 levels, and survived past II months (2/5 still alive past 22 months). All 3 animals in group III remained healthy. The data provided herein suggest that either experimental or natural (due to factors not clear at present) immune stimulation may lead to accelerated lentivirus induced disease progression most likely due to immune suppression and has implications for the understanding of the mechanisms for the rate of disease progression in human HIV-1 infection.