A novel fusion gene, TRIMS-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection
A novel fusion gene, TRIMS-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection
复制标题
猪尾猕猴体内的一种新型融合基因 TRIM5-Cyclophilin A 决定了其对 HIV-1 感染的易感性
DOI：
10.1097/01.aids.0000304692.09143.1b
复制
发表时间：
2007-12-01
期刊：
影响因子：
3.8
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Liao, Cheng-Hong;Kuang, Yi-Qun;Su, Bing
目的：在旧大陆猴中，三重基序Sec（TRIM 5 α）蛋白在病毒进入宿主细胞后赋予对HIV-1感染的抵抗力。然而，猪尾猕猴（Macaca nemestrina）是一个例外，对HIV-1感染易感。本研究旨在探讨短尾猴对HIV-1感染易感性的分子机制。方法：对短尾猴TRIM 5a基因进行测序和表达分析。鉴定了一种新的TRIMS-亲环素A融合基因亚型，并随后将其克隆到pcDNA3.1（+）表达载体中。结果：在短尾猴中发现了一个新的TRIMS-Cyclophilin A融合基因（rnnTRIMCyp），其融合模式与已知的猫头鹰猴融合基因（owITRIMCyp）不同。通过Western印迹证实转染细胞中TRIMCyp蛋白的表达。使用HIV-1（IIIB）和HIV-GFP-VSVG假型病毒的测试表明，mnTRIMCyp不抑制HIV-1复制在各种多样性的infection.Conclusions：mnTRIMCyp融合蛋白不限制HIV-1的复制，这提供了一个潜在的分子机制，可能解释为什么猪尾猕猴容易感染HIV-1，唯一已知的例外，在旧大陆猴。(c)2007年威科健康-利平科特威廉姆斯&威尔金斯。
Objective: In Old World monkeys, the tripartite motif Sec (TRIM5 alpha) protein confers resistance to HIV-1 infection following virus entry into host cells. However, the pig-tailed macaque (Macaca nemestrina) is an exception and is susceptible to HIV-1 infection. This study dissects the molecular mechanism of the pig-tailed macaque's susceptibility to HIV-1 infection.Methods: Genomic sequencing and expression analysis of the TRIM5a gene was conducted in the pig-tailed macaque. A novel TRIMS-Cyclophilin A fusion gene isoform was identified and subsequently cloned into the pcDNA3.1(+) expression vector. This construct was transfected into HeLa-T4 or HeLa cells which were then infected with the HIV-1(IIIB) or HIV-GFP-VSVG pseudotyped virus, to examine the effects of the TRIMS-Cyclophilin A fusion protein on HIV-1 infection.Results: A novel TRIMS-Cyclophilin A fusion gene (rnnTRIMCyp) in the pig-tailed macaque was found and its fusion pattern is different from the known fusion gene in the owl monkey (owITRIMCyp). TRIMCyp protein expression in transfected cells was confirmed by western blotting. The tests using HIV-1(IIIB) and HIV-GFP-VSVG pseudotyped virus indicated that mnTRIMCyp did not inhibit HIV-1 replication at various multiplicities of infection.Conclusions: The mnTRIMCyp fusion protein does not restrict replication of HIV-1, which provides a potential molecular mechanism that might explain why the pig-tailed macaque is prone to HIV-1 infection, the only known exception in Old World monkeys. (c) 2007 Wolters Kluwer Health-Lippincott Williams & Wilkins.