Cao Guang, Nie Wen-Hui, Liu Feng-Liang, Kuang Yi-Qun, Wang Jin-Huan, Su Wei-Ting, Zheng Yong-Tang
Key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
Dongwuxue Yanjiu. 2011 Feb;32(1):40-9. doi: 10.3724/SP.J.1141.2011.01040.
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. TRIM5alpha 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.
缺乏以HIV-1作为攻击病毒的合适动物模型是HIV/AIDS研究的一个主要障碍。HIV-1无法在非人类灵长类动物细胞中复制的一个主要原因是宿主抗病毒限制因子的存在。宿主细胞中的固有抗病毒蛋白被描述为限制因子。了解不同灵长类动物中的限制因子及其机制无疑将促进HIV/AIDS动物模型的开发。TRIM5α是一种重要的限制因子，能够以物种特异性方式限制包括HIV-1在内的多种逆转录病毒的感染。TRIM5-亲环素A（TRIMCyp）基因是在新世界猴和旧世界猴中发现的一个不寻常的TRIM5位点。本文研究了包括阿萨姆猕猴（Macaca assamensis）、藏猕猴（M. thibetana）、短尾猕猴（M. arctoides）和中国恒河猴（M. mulatta）在内的四种灵长类动物（110个样本）的不同TRIMCyp基因型。我们首先发现阿萨姆猕猴中存在TRIM5-CypA融合基因。阿萨姆猕猴的TRIMCyp也像狮尾猕猴的TRIMCyp一样，是由亲环素A假基因cDNA逆转座到TRIM5基因的3'-UTR中产生的。此外，阿萨姆猕猴和狮尾猕猴的TRIMCyp基因之间存在极高的序列同源性。此外，我们还在TRIM5内含子6的3'剪接位点发现了G到T的突变（G/T），这与狮尾猕猴相同。这些结果表明，阿萨姆猕猴可能也像狮尾猕猴一样编码TRIMCyp蛋白，这意味着阿萨姆猕猴可能会被HIV-1感染。因此，阿萨姆猕猴很有可能被用作一种新的HIV/AIDS动物模型。
