Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA.
J Virol. 2013 Jul;87(13):7210-7. doi: 10.1128/JVI.00738-13. Epub 2013 May 1.
Herpes simplex virus 1 (HSV-1) protein ICP27 enables viral mRNA export by accessing the cellular mRNA export receptor TAP/NXF, which guides mRNA through the nuclear pore complex. ICP27 binds viral mRNAs and interacts with TAP/NXF, providing a link to the cellular mRNA export pathway. ICP27 also interacts with the mRNA export adaptor protein Aly/REF, which binds cellular mRNAs and also interacts with TAP/NXF. Studies using small interfering RNA (siRNA) knockdown indicated that Aly/REF is not required for cellular mRNA export, and similar knockdown studies during HSV-1 infection led us to conclude that Aly/REF may be dispensable for viral RNA export. Recently, the structural basis of the interaction of ICP27 with Aly/REF was elucidated at atomic resolution, and it was shown that three ICP27 residues, W105, R107, and L108, interface with the RNA recognition motif (RRM) domain of Aly/REF. Here, to determine the role the interaction of ICP27 and Aly/REF plays during infection, these residues were mutated to alanine, and a recombinant virus, WRL-A, was constructed. Virus production was reduced about 10-fold during WRL-A infection, and export of ICP27 protein and most viral mRNAs was less efficient. We conclude that interaction of ICP27 with Aly/REF contributes to efficient viral mRNA export.
单纯疱疹病毒 1（HSV-1）蛋白 ICP27 通过访问细胞 mRNA 输出受体 TAP/NXF 来实现病毒 mRNA 输出，该受体指导 mRNA 通过核孔复合物。ICP27 结合病毒 mRNA 并与 TAP/NXF 相互作用，为细胞 mRNA 输出途径提供了联系。ICP27 还与 mRNA 输出衔接蛋白 Aly/REF 相互作用，该蛋白结合细胞 mRNA 并与 TAP/NXF 相互作用。使用小干扰 RNA（siRNA）敲低的研究表明，Aly/REF 不是细胞 mRNA 输出所必需的，并且在 HSV-1 感染期间进行的类似敲低研究使我们得出结论，Aly/REF 可能对于病毒 RNA 输出不是必需的。最近，在原子分辨率水平上阐明了 ICP27 与 Aly/REF 相互作用的结构基础，表明 ICP27 的三个残基 W105、R107 和 L108 与 Aly/REF 的 RNA 识别基序（RRM）域相互作用。在这里，为了确定 ICP27 和 Aly/REF 相互作用在感染过程中的作用，这些残基被突变为丙氨酸，并构建了重组病毒 WRL-A。在 WRL-A 感染期间，病毒产量减少了约 10 倍，并且 ICP27 蛋白和大多数病毒 mRNA 的输出效率较低。我们得出结论，ICP27 与 Aly/REF 的相互作用有助于有效的病毒 mRNA 输出。
