缺乏合适的动物模型是制约艾滋病研究取得重大突破的关键瓶颈之一。细胞内的抗病毒蛋白被称为限制因子。研究不同灵长类动物抗HIV-1宿主限制因子的存在形式及作用机制对建立合适AIDS灵长类动物模型有十分重要的意义。TRIM5α是哺乳动物细胞中一种重要和关键的限制因子,它以物种依赖的方式限制包括HIV-1在内的逆转录病毒的感染。TRIM5-CypA融合基因是存在于新大陆猴与旧大陆猴中的一种独特的TRIM5基因形式。为了研究不同灵长类动物TRIM5基因的存在方式,该文对熊猴、藏酋猴、红面猴及中国恒河猴4个物种共110只灵长类动物进行了TRIM5-CypA融合模式的研究。首次发现熊猴也存在TRIM5-CypA基因融合现象。熊猴TRIMCyp融合基因形成模式类似于北平顶猴TRIMCyp融合基因模式,即CypA假基因的cDNA序列通过逆转座方式插入到TRIM5基因的3'-UTR区域。基因序列分析表明,该基因与北平顶猴相应基因序列高度相似;并且其TRIM5内含子6的3'-剪接位点也相应存在G-to-T突变现象(G/T)。这提示熊猴也极有可能像北平顶猴一样表达TRIM5-CypA融合蛋白,从而导致熊猴可能跟北平顶猴一样可能被HIV-1感染。因此,熊猴极有希望成为一种新的HIV/AIDS灵长类动物模型。
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.TRIM5α 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 TRIM5 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.mulatta) 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 TRIM5 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 TRIM5 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.