Diaz-Griffero Felipe, Vandegraaff Nick, Li Yuan, McGee-Estrada Kathleen, Stremlau Matthew, Welikala Sohanya, Si Zhihai, Engelman Alan, Sodroski Joseph
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Virology. 2006 Aug 1;351(2):404-19. doi: 10.1016/j.virol.2006.03.023. Epub 2006 May 2.
In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5alpha with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain.
在夜猴中，一次逆转座事件使编码逆转录病毒限制因子TRIM5α的基因被编码TRIMCyp的基因所取代，TRIMCyp是TRIM5的RING、B盒2和卷曲螺旋结构域与亲环素A的融合体。TRIMCyp通过一种依赖亲环素A部分与人类免疫缺陷病毒（HIV-1）衣壳蛋白相互作用的机制来限制HIV-1感染。在此，我们表明TRIMCyp可以限制除HIV-1之外的其他逆转录病毒的感染，这为TRIMCyp基因在夜猴谱系中的进化保留提供了解释。TRIMCyp介导的对HIV-1感染的阻断发生在逆转录的最早步骤之前。TRIMCyp介导的限制至少涉及两种功能：（1）衣壳结合，对于保留卷曲螺旋和亲环素A结构域的三聚体TRIMCyp蛋白，这种结合最有效；（2）一种依赖B盒2结构域的效应功能。
