灵长类动物中TRIMCyp融合基因模式及对逆转录病毒复制的限制作用

The primate TRIMCyp fusion genes and mechanism of restricting retroviruses replication

TRIM5-CypA融合基因(TRIMCyp)是一种独特的TRIM5基因形式。迄今已发现新大陆猴中包括鹰猴在内的夜猴属所有代表种,以及在北平顶猴、巽他平顶猴、食蟹猴、印度恒河猴和熊猴等旧大陆猴中均存在这种基因融合现象,但在新大陆猴与旧大陆猴中的TRIMCyp融合基因的基因融合模式和表达剪接方式不同。新大陆猴TRIMCyp融合基因是由CypA假基因的cDNA序列通过LINE-1逆转座子介导的逆转座方式插入至TRIM5α基因的第7和第8外显子之间的内含子中形成,而旧大陆猴TRIMCyp融合基因则是由CypA假基因的cDNA序列以相似的逆转座方式插入至TRIM5基因的3'非翻译区(untranslatedregions,UTR)形成。TRIMCyp融合基因在不同灵长类动物中的存在比例、基因型、TRIMCyp融合蛋白的表达以及对逆转录病毒的限制活性均有所差异。鹰猴和平顶猴的TRIMCyp融合基因研究较多,鹰猴TRIMCyp融合蛋白可能以与TRIM5α相似机制限制HIV-1的感染,而平顶猴TRIMCyp融合蛋白则丧失了限制HIV-1的作用。这两个功能截然不同的融合基因为TRIM5α作用机制研究提供了难得的实验材料,也为建立HIV-1感染的新型灵长类动物艾滋病模型奠定了科学依据。该文综述了TRIMCyp融合基因在灵长类动物中的分布、存在形式及其限制逆转录病毒复制的作用机制等方面的研究情况。

TRIM5-cyclophilin A（TRIMCyp） fusion gene is an unusual TRIM5 locus.At present,this fusion phenomenon has been found in the representative species which contain owl monkey（Aotus trivirgatus） of Aotus genus that belongs to New World monkeys and Old World monkeys such as Northern pig-tailed macaque（M.leonina）,Sunda pig-tailed macaque（M.nemestrina）,Crab-eating macaque（M.fascicularis）,Indian rhesus macaque（M.mulatta） and Assam macaque（M.assamensis）,etc.But the fusion mode and transcription splicing pattern of TRIMCyp fusion gene are different between New World and Old World monkeys.The TRIMCyp fusion gene of New World monkeys is formed by inserting a CypA pseudogene cDNA sequence into the region between exon 7 and exon 8 of the TRIM5 locus through retrotransposition.However the TRIMCyp fusion gene of Old World monkeys results from the retrotransposition of a CypA pseudogene cDNA into 3＇ terminal or 3＇-UTR of TRIM5 gene.The distributions,genotypes,expression and restricting activities against different retroviruses of TRIMCyp were different across species of primates.Moreover,most of the researches focused on the TRIMCyp fusion gene of owl monkey and pig-tailed macaque and found that they may play very important roles in restricting HIV-1 replication and determine the susceptibility to HIV-1 infection.It was reported that the TRIMCyp protein of owl monkey could inhibit HIV-1 infection in a similar way as TRIM5α,but TRIMCyp protein of pig-tailed monkey loss the restricting activity to HIV-1 infection.Here we reviewed the distributions,genotypes and restriction mechanism for inhibiting retroviruses replication of TRIMCyp fusion gene in primates.