Identification of the TRIM5/TRIMCyp heterozygous genotype in Macaca assamensis
Identification of the TRIM5/TRIMCyp heterozygous genotype in Macaca assamensis
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DOI：
10.3724/sp.j.1141.2011.01040
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发表时间：
2011-02-01
影响因子：
4.9
通讯作者：
Zheng Yong-Tang
中科院分区：
文献类型：
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作者：
Cao Guang;Nie Wen-Hui;Zheng Yong-Tang
缺乏利用HIV-1作为挑战病毒的适当动物模型是艾滋病毒/艾滋病研究的主要障碍。HIV-1在非人灵长类动物细胞中无法复制的一个主要原因是宿主抗病毒限制因子的存在。宿主细胞内固有的抗病毒蛋白被描述为限制因子。了解不同灵长类动物的限制因子及其作用机制，无疑将促进HIV/AIDS动物模型的开发。TRIM5 α是一个重要的限制性因子，可以以一种特定的方式限制包括HIV-1在内的几种逆转录病毒的感染。trim5 -亲环蛋白A （TRIMCyp）基因是在新旧大陆猴中发现的一个罕见的TRIMS基因座。本文以西藏猕猴（thibetana）、短尾猕猴（M. arctoides）和中国恒河猴（M. mulatto）为研究对象。我们首次发现TRIM5-CypA融合基因存在于阿萨姆稻中。M. assamensis的TRIMCyp也与M. leonina的TRIMCyp一样，是由CypA假基因cDNA反转录到TRIMS基因的3'-UTR中而产生的。此外，阿萨姆稻和狮子稻的TRIMCyp基因具有极高的序列同源性。此外，我们还在TRIMS内含子6的3'剪接位点发现了G-to-T突变（G/T），与M. leonina相同。这些结果表明，阿萨姆密螺旋体也可能像狮子螺旋体一样编码TRIMCyp蛋白，这意味着阿萨姆密螺旋体可能感染了HIV-1。因此，阿萨姆支原体很有可能作为新的HIV/AIDS动物模型。
The lack of appropriate animal models that utilizes HIV-1 as the challenge virus is a major impediment to HIV/AIDS research. A major reason underlying the inability of HIV-1 to replicate in nonhuman primate cells is the existence of host antiviral restriction factors. The intrinsic antiviral proteins in host cells are described as restriction factors. The understanding of restriction factors and their mechanism in different primates would undoubtedly facilitate the development of HIV/AIDS animal models. TRIM5 alpha is an important restriction factor and can restrict the infection of several retroviruses including HIV-1 in a species-specific fashion. TRIM5-cyclophilin A (TRIMCyp) gene is an unusual TRIMS locus found in New World and Old World monkeys. The different TRIMCyp genotypes of four primates (110 samples) including assam macaque (Macaca assamensis), tibetan macaque (M. thibetana), stump-tailed macaque (M. arctoides) and Chinese rhesus macaques (M. mulatto) were studied in this paper. We firstly found that TRIM5-CypA fusion gene exist in M. assamensis. The TRIMCyp of M. assamensis also results from the retrotransposition of CypA pseudogene cDNA into 3'-UTR of TRIMS gene like TRIMCyp of M. leonina. Moreover, there is an extremely high sequence homology between TRIMCyp genes from M. assamensis and M. leonina. Besides, we also found the G-to-T mutation (G/T) in the 3'splicing site of TRIMS intron 6, which was identical to M. leonina. These results indicate M. assamensis may also encode TRIMCyp protein like M. leonine, which imply M. assamensis might be infected by HIV-1. Therefore, it is very possible that M. assamensis will be used as a new HIV/AIDS animal model.