Nup358 and Transportin 1 Cooperate in Adenoviral Genome Import
Nup358 and Transportin 1 Cooperate in Adenoviral Genome Import
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DOI：
10.1128/jvi.00164-20
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发表时间：
2020-05-01
影响因子：
5.4
通讯作者：
Wodrich, Harald
中科院分区：
文献类型：
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作者：
Carlon-Andres, Irene;Lagadec, Floriane;Wodrich, Harald
病毒基因组的核输入是腺病毒（AdV）生命周期中的重要步骤，需要可溶性细胞因子以及核孔复合物（NPC）蛋白。我们通过进行耗竭/重建实验和腺病毒基因组导入的时间分辨定量来解决腺病毒基因组递送过程中细胞质核孔蛋白Nup 358的作用。Nup 358-耗尽的细胞显示出腺病毒基因组的核输入效率降低，并且核输入受体转运蛋白1在这些条件下变得限速。此外，我们确定了Nup 358的最小N-末端区域，其足以补偿输入缺陷。我们的数据支持一个模型，其中Nup 358作为一个组装平台，促进运输复合物的形成，使腺病毒利用生理蛋白质进口途径加速其DNA.IMPORTANCE运输核基因组的进口是一个必不可少的步骤，启动生产性感染几个核复制DNA病毒。另一方面，DNA不是一种生理性核输入底物;因此，病毒必须利用现有的生理性运输途径。在这里，我们表明腺病毒使用核孔蛋白Nup 358来增加腺病毒基因组导入的效率。在其缺失的情况下，基因组输入效率降低，并且转运受体转运蛋白1变得限速。我们表明，Nup 358的N-末端的一半是足以驱动基因组的进口，并确定一个转运蛋白1结合区域。在我们的模型中，腺病毒基因组导入利用现有的蛋白质导入途径，Nup 358作为转运复合物的组装平台。
Nuclear import of viral genomes is an important step during the life cycle of adenoviruses (AdV), requiring soluble cellular factors as well as proteins of the nuclear pore complex (NPC). We addressed the role of the cytoplasmic nucleoporin Nup358 during adenoviral genome delivery by performing depletion/reconstitution experiments and time-resolved quantification of adenoviral genome import. Nup358-depleted cells displayed reduced efficiencies of nuclear import of adenoviral genomes, and the nuclear import receptor transportin 1 became rate limiting under these conditions. Furthermore, we identified a minimal N-terminal region of Nup358 that was sufficient to compensate for the import defect. Our data support a model where Nup358 functions as an assembly platform that promotes the formation of transport complexes, allowing AdV to exploit a physiological protein import pathway for accelerated transport of its DNA.IMPORTANCE Nuclear import of viral genomes is an essential step to initiate productive infection for several nuclear replicating DNA viruses. On the other hand, DNA is not a physiological nuclear import substrate; consequently, viruses have to exploit existing physiological transport routes. Here, we show that adenoviruses use the nucleoporin Nup358 to increase the efficiency of adenoviral genome import. In its absence, genome import efficiency is reduced and the transport receptor transportin 1 becomes rate limiting. We show that the N-terminal half of Nup358 is sufficient to drive genome import and identify a transportin 1 binding region. In our model, adenovirus genome import exploits an existing protein import pathway and Nup358 serves as an assembly platform for transport complexes.