Chuang L F, Blackbourn D J, Chuang A J, Killam K F, Liu X, Li Y, Kung H F, Chuang R Y
Department of Medical Pharmacology and Toxicology, University of California, Davis 95616, USA.
Cell Mol Biol Res. 1994;40(7-8):661-9.
Infection with the macaque strain of the simian immunodeficiency virus (SIVmac) induces simian immunodeficiency syndrome in rhesus macaques. This report describes the isolation and identification of antigenic variants of SIVmac in one of the infected monkeys (macaque #22803). Eight naive rhesus monkeys were inoculated with a titered viral stock of the molecularly cloned SIVmac239. Standard serological analysis revealed that all but two were seroconverted. Western blot analysis confirmed the seronegativity of macaque #22803. In addition, sera recovered from this monkey were not able to neutralize the parent SIVmac239. However, virus could be isolated from all of the infected animals, including macaque #22803. Sera recovered were reactive to the autologous virus. The results suggest that the virus from macaque #22803 may have undergone extensive antigenic shift in vivo. To test this hypothesis, a portion of the gag gene was amplified by the polymerase chain reaction (PCR), cloned, and sequenced. Sequence analysis revealed amino acid changes that were clustered between amino acids 200-245. Evaluation of the possible selective pressures contributing to the observed viral mutation revealed that in comparison with the other SIVmac239-infected monkeys, macaque #22803 produced an unusually high T cell proliferative response toward mitogen stimulation before infection, and continued to display a persistently high plasma viremia titer after infection.
感染猕猴免疫缺陷病毒（SIVmac）的猕猴株会在恒河猴中引发猴免疫缺陷综合征。本报告描述了在其中一只受感染的猴子（猕猴#22803）中分离和鉴定SIVmac的抗原变异体。八只未感染的恒河猴接种了分子克隆的SIVmac239的滴定病毒原液。标准血清学分析显示，除两只外，其他所有猴子都发生了血清转化。蛋白质印迹分析证实了猕猴#22803的血清阴性。此外，从这只猴子身上采集的血清无法中和亲本SIVmac239。然而，病毒可以从所有受感染的动物中分离出来，包括猕猴#22803。采集的血清与自体病毒发生反应。结果表明，来自猕猴#22803的病毒可能在体内发生了广泛的抗原漂移。为了验证这一假设，通过聚合酶链反应（PCR）扩增了一部分gag基因，进行克隆并测序。序列分析揭示了氨基酸变化集中在200-245位氨基酸之间。对导致观察到的病毒突变的可能选择压力的评估显示，与其他感染SIVmac239的猴子相比，猕猴#22803在感染前对丝裂原刺激产生了异常高的T细胞增殖反应，并且在感染后继续表现出持续较高的血浆病毒血症滴度。
