Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis).
Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis).
复制标题
DOI：
10.1099/vir.0.038075-0
复制
发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Nakayama EE
中科院分区：
文献类型：
--
作者：
Saito A;Kono K;Nomaguchi M;Yasutomi Y;Adachi A;Shioda T;Akari H;Nakayama EE
抗逆转录病毒因子三方基序蛋白5(TRIM5)基因衍生异构体(TRIMCyp)至少存在于三种东半球猕猴身上：恒河猴(Macaca Mulatta)、猪尾猕猴(Macaca Nomestrina)和食蟹猴(Macaca Fascular Aris)。虽然TRIMCyp在恒河猴和猪尾猕猴中的频率已经得到了很好的研究，但TrIMCyp在食蟹猴中的频率和流行率仍然没有明确的阐明。本研究以食蟹猴为研究对象，研究了α/TRIMCyp的地理多样性和遗传多样性，并与其抗慢病毒活性进行了比较。研究发现，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。食蟹猴TIMCyp的主要和次要单倍型也在亲环素A结构域存在单核苷酸多态。结果表明，TrIMCyp的主要单倍型抑制HIV-1，但不抑制HIV-2，而次要单倍型抑制HIV-2，但不抑制HIV-1。TRIMCyp的主要单倍型不限制嗜猴的HIV-1克隆NL-DT5R，该克隆包含一个衣壳，在α-螺旋4和5之间以及整个vif基因之间有一个与猴免疫缺陷病毒衍生的环。这些结果表明，TRIMCyp基因的多态性影响其抗慢病毒活性。总体而言，本研究结果将有助于我们了解食蟹猴TIMCyp的遗传背景，以及构成灵长类慢病毒物种屏障的宿主因素。
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.
登录
查看更多内容
DOI：
10.1073/pnas.0608289103
发表时间：
2006-11-07
影响因子：
11.1
作者：
Kamada, Kazuya;Igarashi, Tatsuhiko;Adachi, Akio
通讯作者：
Adachi, Akio
影响因子：
5.8
作者：
Saito, Akatsuki;Nomaguchi, Masako;Akari, Hirofumi
通讯作者：
Akari, Hirofumi
影响因子：
3.2
作者：
Kita, Yuki F.;Hosomichi, Kazuyoshi;Shiina, Takashi
通讯作者：
Shiina, Takashi
影响因子：
5.4
作者：
Dietrich, Elizabeth A.;Brennan, Greg;Hu, Shiu-Lok
通讯作者：
Hu, Shiu-Lok
影响因子：
6.7
作者：
Ylinen LM;Price AJ;Rasaiyaah J;Hué S;Rose NJ;Marzetta F;James LC;Towers GJ
通讯作者：
Towers GJ