平顶猴TRIM5α基因变异影响其抗HIV-1功能  

Anti-virus functions of the gene TRIM5α is affected by mutations in macaca nemestrina

作　　者：刘红亮[1] 郑永唐[2] 况轶群[2] 马远方[1] 

机构地区：[1]河南大学医学院河南大学免疫学研究所河南大学天然药物与免疫工程省级重点实验室,开封475004 [2]中国科学院昆明动物研究所分子免疫与药理实验室,昆明650032

出　　处：《中国免疫学杂志》2008年第10期906-910,916,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金(30571697);河南省AIDS科技攻关项目(2006037);河南省医学科技攻关项目(200803085)资助

摘　　要：目的:解释平顶猴成为唯一能够被HIV-1感染的旧大陆猴以及在被SIV感染时出现较其他旧大陆猴严重临床症状的原因。方法:参考人TRIM5α基因的结构和序列合成引物,以平顶猴DNA为模板,分别扩增其TRIM5α基因编码序列的所有外显子。利用生物学软件分析获得的编码序列,分析在已经明确与TRIM5α抗病毒功能密切相关的几个位点上是否发生可能影响其功能的突变。结果:在平顶猴基因组上CypA基因融合到TRIM5α基因第八外显子的下游,融合方式与在鹰猴中发现的CypA与TRIM5α的融合方式完全不同。恒河猴TRIM5α基因具有限制HIV-1复制的功能,第332位脯氨酸对其抗病毒功能非常重要,但在平顶猴的TRIM5α上,该氨基酸突变成谷氨酰胺;第335位以后8个氨基酸对恒河猴TRIM5α抗病毒功能也有重要影响,但在平顶猴的TRIM5α上,与其对应的氨基酸片段不仅缺失了两个氨基酸,还有两个氨基酸发生突变,附近区域还有另外两个发生突变。在平顶猴TRIM5α基因的Coiled-Coil结构域插入了13个氨基酸,但没有影响到编码框。结论:在平顶猴的基因组上CypA与TRIM5α的融合以及平顶猴TRIM5α基因抗病毒功能关键位点上的氨基酸突变可能影响其抗病毒功能,是其成为唯一能够被HIV-1感染的旧大陆猴以及在被SIV感染时出现较其他旧大陆猴严重临床症状的重要原因。Objective：To explain why HIV-1 only infects Macaca nemestrina among Old World monkeys,and why the more serious clinical symptoms occur in Macaca nemestrina due to infection of SIV than in other Old World monkeys.Methods：According to the reported gene sequences of human TRIM5a,we designated primers to amplify all the encoding exons of TRIM5a gene from Macaca nemestrina genomic DNA,analyzed the mutations in the epitopes related to the anti-virus function using biosoftware.Results：In the genomic DNA of Macaca nemestrina,we found the Cyclophilin A （CypA） gene retrotranslocated to the down stream of the exon No.8 of TRIM5a gene,which was different from the gene organization in owl monkey genomic sequence.It was reported the Pro residue in position 332 of rhesus monkey TRIM5a protein plays an important role in blocking HIV-1 virus replication in rhesus monkey,but in Macaca nemestrina,this residue was mutated to Gln.From position 335 to 342 in TRIM5a protein in Macaca nemestrina,there were 2 residues missed and 2 residue mutation.Also,there were 2 residue mutation in the near region,but in rhesus monkey,this region is involved in the function of antivirus.In the genomic sequence of TRIM5a gene in Macaca nemestrina,we also found an insertion of 13 residues in the Coiled-Coil domain with its function still unknown,which doesn’t affect the downstream open reading frame.Conclusion：Based on the sequence analysis of TRIM5a gene of Macaca nemestrina,we can conclude that the mutation and mission of key residues related to the antivirus function may be the reason for the susceptibility and the severity clinical symptoms of Macaca nemestrina to SIV infection.

关 键 词：HIV-1 平顶猴TRIM5α 基因突变 抗病毒功能 

分 类 号：R392[医药卫生—免疫学]