Differential interaction between human and murine Crm1 and lentiviral Rev proteins.
Differential interaction between human and murine Crm1 and lentiviral Rev proteins.
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DOI：
10.1016/j.virol.2017.09.027
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发表时间：
2018-01-01
期刊：
影响因子：
3.7
通讯作者：
Sutton RE
中科院分区：
文献类型：
--
作者：
Yue Y;Coskun AK;Jawanda N;Auer J;Sutton RE
小鼠对HIV复制有多种障碍，包括未剪接和部分剪接的病毒mRNA核输出的阻断。在人体中，Rev与Rev反应元件和人（h）Crm 1结合，促进含RRE病毒RNA的核输出。在这方面，小鼠（m）Crm 1的功能不如hCrm 1。在这里，我们证明，在生化实验中，mCrm 1未能与HIV Rev相互作用，而hCrm 1。在人类细胞的遗传实验中，我们观察到mCrm 1和hCrm 1之间存在适度但显着的差异效应，这也适用于测试的其他慢病毒Rev。三重突变体hCrm 1 P411 T-M412 V-F414 S的行为与mCrm 1相似，而mCrm 1与T411 P-V412 M-S414 F恢复了一些活性，尽管不能排除其他残基对其功能的贡献。在鼠细胞中观察到类似的结果。这表明hCrm 1和mCrm 1与许多慢病毒Rev之间存在差异性相互作用，这可能部分解释了小鼠中的HIV复制缺陷。
Mice have multiple obstacles to HIV replication, including a block of unspliced and partially spliced viral mRNA nuclear export. In human, Rev binds to the Rev-response element and human (h) Crm1, facilitating nuclear export of RRE-containing viral RNAs. Murine (m) Crm1 is less functional than hCrm1 in this regard. Here we demonstrated that in biochemical experiments mCrm1 failed to interact with HIV Rev whereas hCrm1 did. In genetic experiments in human cells, we observed a modest but significant differential effect between mCrm1 and hCrm1, which was also true of other lentiviral Revs tested. Triple mutant hCrm1 P411T-M412V-F414S behaved similarly to mCrm1, whereas mCrm1 with T411P-V412M-S414F regained some activity, although contribution of additional residues to its function can not be excluded. Similar results were observed in murine cells. This suggests a differential interaction between hCrm1 and mCrm1 and many lentiviral Revs, which may partially explain the HIV replicative defect in mice.
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