The ability of multimerized cyclophilin A to restrict retrovirus infection
The ability of multimerized cyclophilin A to restrict retrovirus infection
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DOI：
10.1016/j.virol.2007.04.034
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发表时间：
2007-10-10
期刊：
影响因子：
3.7
通讯作者：
Sodroski, Joseph
中科院分区：
文献类型：
--
作者：
Javanbakht, Hassa. N.;Diaz-Griffero, Felipe;Sodroski, Joseph
在猫头鹰猴中，灵长类的典型逆转录病毒限制因子TRIM 5 α被TRIMCyp取代。TRIMCyp由与亲环蛋白A融合的TRIMS RING、B-box 2和卷曲螺旋结构域以及插入接头区域组成。TRIMCyp限制逆转录病毒的感染，例如人类免疫缺陷病毒（HIV-1）和猫免疫缺陷病毒（FIV），具有可以结合亲环蛋白A的衣壳。TRIMS卷曲螺旋促进TRIMCyp的三聚化。在这里，我们表明，亲环素A是寡聚体与异源多聚体融合的结果表现出显着的抗逆转录病毒活性。将TRIMS RING、B-box 2和Linker 2添加到寡聚亲环素A中产生了具有接近野生型TRIMCyp的抗逆转录病毒活性的蛋白质。多聚化增加亲环素A与HIV-1衣壳的结合，促进衣壳加速脱壳和限制感染。(C)2007年爱思唯尔公司All rights reserved.
In owl monkeys, the typical retroviral restriction factor of primates, TRIM5 alpha, is replaced by TRIMCyp. TRIMCyp consists of the TRIMS RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIMS coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIMS RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection. (C) 2007 Elsevier Inc. All rights reserved.