The effect of exon 7 deletion during the evolution of TRIMCyp fusion proteins on viral restriction, cytoplasmic body formation and multimerization.
The effect of exon 7 deletion during the evolution of TRIMCyp fusion proteins on viral restriction, cytoplasmic body formation and multimerization.
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TRIMCyp 融合蛋白进化过程中外显子 7 缺失对病毒限制、细胞质体形成和多聚化的影响
DOI：
10.1371/journal.pone.0121666
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zheng YT
中科院分区：
文献类型：
--
作者：
Liu FL;Kuang YQ;Mu D;Zheng HY;Zhu JW;Zheng YT
TRIMCyp是一种由TRIM5基因产物和反转录的亲环蛋白a （CypA）组成的融合蛋白。两种具有不同抗hiv -1活性的灵长类TRIMCyp融合蛋白在猫头鹰猴和旧大陆猴中独立进化。此外，旧大陆猴TRIMCyps缺乏编码link2区域氨基酸的外显子7。先前对TRIM5α的研究表明，该区域影响抗逆转录病毒活性、细胞质体形成和多聚。外显子7缺失对TRIMCyp功能的影响尚不清楚。在本研究中，我们发现猫头鹰猴TRIMCyp （omTRIMCyp）的细胞质体和多聚体与北方长尾猕猴TRIMCyp （npmTRIMCyp）不同。此外，我们证明了外显子7的缺失影响细胞质体的形成和多聚。此外，我们意外地发现omTRIMCyp和npmTRIMCyp的两个嵌合蛋白无法阻断HIV-1的复制，尽管omTRIMCyp中存在CypA。进一步的研究表明，细胞质体和自发多聚不是TRIMCyp抗hiv -1活性的原因。此外，当CypA结构域能够识别并结合HIV-1衣壳时，有效的病毒限制与更高数量的单体TRIMCyp相关。我们的研究结果表明，在TRIMCyp的进化过程中，外显子7的缺失影响了其功能。
TRIMCyp is a fusion protein consisting of the TRIM5 gene product and retrotransposed Cyclophilin A (CypA). Two primate TRIMCyp fusion proteins with varying anti-HIV-1 activities independently evolved in owl monkeys and Old World monkeys. In addition, Old World monkey TRIMCyps lack exon7, which encodes amino acids in the Linker2 region. Previous studies on TRIM5α indicated that this region affects anti-retroviral activity, cytoplasmic body formation, and multimerization. The effects of exon7 deletion on the functions of the TRIMCyp are unclear. In this study, we found that the cytoplasmic bodies and multimers of owl monkey TRIMCyp (omTRIMCyp) are different from those of northern pig-tailed macaque TRIMCyp (npmTRIMCyp). In addition, we demonstrated that exon7 deletion affected cytoplasmic body formation and multimerization. Moreover, we unexpectedly found two chimeric proteins of omTRIMCyp and npmTRIMCyp that failed to block HIV-1 replication, despite the presence of CypA in omTRIMCyp. Further studies indicated that the cytoplasmic bodies and spontaneous multimerization were not responsible for TRIMCyp anti-HIV-1 activity. Moreover, potent viral restriction is associated with higher amounts of monomeric TRIMCyp when the CypA domain is able to recognize and bind to the HIV-1 capsid. Our results suggested that the deletion of exon7 during the evolution of TRIMCyp affected its function.
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影响因子：
3.3
作者：
Campbell, Edward M.;Dodding, Mark P.;Hope, Thomas J.
通讯作者：
Hope, Thomas J.
影响因子：
3.7
作者：
Javanbakht, Hassa. N.;Diaz-Griffero, Felipe;Sodroski, Joseph
通讯作者：
Sodroski, Joseph
影响因子：
4.9
作者：
Cao Guang;Nie Wen-Hui;Zheng Yong-Tang
通讯作者：
Zheng Yong-Tang
影响因子：
64.8
作者：
Pertel, Thomas;Hausmann, Stephane;Morger, Damien;Zueger, Sara;Guerra, Jessica;Lascano, Josefina;Reinhard, Christian;Santoni, Federico A.;Uchil, Pradeep D.;Chatel, Laurence;Bisiaux, Aurelie;Albert, Matthew L.;Strambio-De-Castillia, Caterina;Mothes, Walther;Pizzato, Massimo;Gruetter, Markus G.;Luban, Jeremy
通讯作者：
Luban, Jeremy
影响因子：
3.7
作者：
Sastri J;O'Connor C;Danielson CM;McRaven M;Perez P;Diaz-Griffero F;Campbell EM
通讯作者：
Campbell EM