Division of Retrovirology, National Institute for Biological Standards and Control, A Centre of the Health Protection Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK.
Immunogenetics. 2012 Apr;64(4):267-78. doi: 10.1007/s00251-011-0585-x. Epub 2011 Nov 29.
The TRIM5α restriction factor can protect some species of monkeys, but not humans, from HIV infection. It has also emerged that some monkeys have a cyclophilin A domain retrotransposed into the TRIM5 locus resulting in the expression of a TRIMCyp protein with anti-retroviral activity. A high degree of sequence variation in the primate TRIM5 gene has been reported that varies between populations of rhesus macaques, a widely used non-human primate model of HIV/AIDS, and recently shown to correlate with susceptibility to simian immunodeficiency viruses in this species. Cynomolgus macaques are also used widely in HIV research. A non-indigenous population on Mauritius has highly restricted genetic diversity compared with macaques from Indonesia. The relative allelic diversity of TRIM5α and TRIMCyp within these two sub-populations may impact on the susceptibility of the macaques to simian immunodeficiency virus thereby influencing the outcome of studies using these monkeys. We sought to establish the genetic diversity of these alleles in cynomolgus macaques. We identified seven TRIM5α alleles in Indonesian macaques, three of which are novel, but only three in the Mauritian-origin macaques. Strikingly, 87% of Indonesian, but none of the Mauritian macaques, possessed a retrotransposed Cyp domain. A splice acceptor site single-nucleotide polymorphism that allows formation of a TRIMCyp protein was absent for the TRIM5α alleles found in the Mauritian macaques. The level of allelic diversity reported here is greater than previously proposed for cynomolgus macaque species.
TRIM5α 限制因子可以保护某些种类的猴子免受 HIV 感染,但不能保护人类。此外,一些猴子的 cyclophilin A 结构域被反转录到 TRIM5 基因座,导致表达具有抗病毒活性的 TRIMCyp 蛋白。已报道灵长类动物 TRIM5 基因的高度序列变异,这种变异在恒河猴种群之间存在差异,恒河猴是 HIV/AIDS 的广泛使用的非人类灵长类动物模型,最近的研究表明,这种变异与该物种中对猿猴免疫缺陷病毒的易感性相关。食蟹猴也广泛用于 HIV 研究。与来自印度尼西亚的猴子相比,毛里求斯的非本土种群具有高度受限的遗传多样性。这两个亚种群中 TRIM5α 和 TRIMCyp 的相对等位基因多样性可能会影响猴子对猿猴免疫缺陷病毒的易感性,从而影响使用这些猴子进行的研究结果。我们试图确定这些等位基因在食蟹猴中的遗传多样性。我们在印度尼西亚的猴子中鉴定出 7 种 TRIM5α 等位基因,其中 3 种是新的,但在毛里求斯起源的猴子中只有 3 种。引人注目的是,87%的印度尼西亚猴子,但没有毛里求斯的猴子,具有反转录的 Cyp 结构域。在毛里求斯猴子中发现的 TRIM5α 等位基因中,不存在允许形成 TRIMCyp 蛋白的剪接受体单核苷酸多态性。这里报道的等位基因多样性水平高于以前提出的食蟹猴种。