Primate Research Institute, Kyoto University, Inuyama 484-8506, Japan.
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
J Gen Virol. 2012 Mar;93(Pt 3):594-602. doi: 10.1099/vir.0.038075-0. Epub 2011 Nov 23.
The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses.
抗病毒因子三结构域蛋白 5（TRIM5）基因衍生的异构体（TRIMCyp）已在至少三种旧世界猴中发现：恒河猴（Macaca mulatta）、猪尾猴（Macaca nemestrina）和食蟹猴（Macaca fascicularis）。虽然在恒河猴和猪尾猴中对 TRIMCyp 的频率进行了很好的研究，但在食蟹猴中 TRIMCyp 的频率和流行率仍有待明确阐明。在这里，与抗慢病毒活性相比，研究了食蟹猴 TRIM5α/TRIMCyp 的地理和遗传多样性。结果发现，菲律宾人群中 TRIMCyp 的频率明显高于印度尼西亚和马来西亚人群。还发现了具有环孢菌素 A 结构域单核苷酸多态性的食蟹猴 TRIMCyp 的主要和次要单倍型。还检查了 TRIMCyp 多态性的功能意义，结果表明，TRIMCyp 的主要单倍型抑制人类免疫缺陷病毒 1（HIV-1）而不抑制 HIV-2，而 TRIMCyp 的次要单倍型抑制 HIV-2 而不抑制 HIV-1。TRIMCyp 的主要单倍型不限制含有源自猿猴免疫缺陷病毒的α螺旋 4 和 5 之间环和整个 vif 基因的包膜的猴嗜性 HIV-1 克隆 NL-DT5R。这些结果表明，TRIMCyp 的多态性影响其抗慢病毒活性。总的来说，这项研究的结果将有助于我们了解食蟹猴 TRIMCyp 的遗传背景，以及构成灵长类慢病毒种间屏障的宿主因素。
