论文部分内容阅读
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 a suitable animal model is one of the key bottlenecks that have made major breakthroughs in AIDS research. Antiviral proteins in cells are called limiting factors. It is of great significance to study the existence and mechanism of the restriction factor against HIV-1 in different primates to establish a suitable AIDS primate model. TRIM5α is an important and critical limiting factor in mammalian cells that limits retrovirus infection, including HIV-1, in a species-dependent manner. The TRIM5-CypA fusion gene is a unique TRIM5 gene present in the New World and Old World monkeys. In order to study the existence of TRIM5 genes in different primates, TRIM5-CypA fusion patterns of 110 primate species from four species of bears, monkey, red monkey and Chinese rhesus monkeys were studied . The first discovery of bear monkey also exists TRIM5-CypA gene fusion phenomenon. The pattern of TRIMCyp fusion gene in Begonia monkey is similar to the TRIMCyp fusion gene pattern in Peking Peacock monkey. The cDNA sequence of CypA pseudogene is inserted into the 3’-UTR region of TRIM5 gene by retrotransposon. The gene sequence analysis showed that the gene was highly similar to the corresponding gene of Pentaphylida, and the G-to-T mutation (G / T) was found in the 3’-splice site of TRIM5 intron 6. This suggests that bear beasts are also likely to express TRIM5-CypA fusion protein like Pekingese, resulting in the possibility that bear bears may be infected with HIV-1 as Pekingese. Therefore, the bear monkey is very promising to become a new model of HIV / AIDS primate.