NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway.
NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway.
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DOI：
10.3390/v8080209
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发表时间：
2016-07-28
期刊：
影响因子：
--
通讯作者：
Aida Y
中科院分区：
文献类型：
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作者：
Chutiwitoonchai N;Aida Y
流感仍然是一个严重的全球性公共卫生问题。感染后，病毒基因组RNA在细胞核中复制并包装成病毒核糖核蛋白，然后通过细胞染色体区域维持1（CRM 1）依赖性途径输出到细胞质中进行进一步组装和出芽。然而，流感病毒的核输出机制仍存在争议。在这里，我们确定细胞核转运因子2（NTF 2）样输出蛋白1（NXT 1）作为一种新的结合伙伴的核蛋白（NP），刺激NP介导的核出口通过CRM 1依赖的途径。NXT 1敲除细胞表现出病毒复制动力学降低和核积累的病毒RNA和NP。相比之下，NXT 1过表达促进核出口的NP在CRM 1依赖的方式。下拉试验表明NXT 1，NP和CRM 1复合物的形成，并证明NXT 1结合到NP的C-末端区域。这些发现揭示了流感病毒核输出的独特机制，并将NXT 1/NP相互作用确定为抗病毒药物开发的潜在靶点。
Influenza remains a serious worldwide public health problem. After infection, viral genomic RNA is replicated in the nucleus and packed into viral ribonucleoprotein, which will then be exported to the cytoplasm via a cellular chromosome region maintenance 1 (CRM1)-dependent pathway for further assembly and budding. However, the nuclear export mechanism of influenza virus remains controversial. Here, we identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway. NXT1-knockdown cells exhibit decreased viral replication kinetics and nuclear accumulated viral RNA and NP. By contrast, NXT1 overexpression promotes nuclear export of NP in a CRM1-dependent manner. Pull-down assays suggest the formation of an NXT1, NP, and CRM1 complex, and demonstrate that NXT1 binds to the C-terminal region of NP. These findings reveal a distinct mechanism for nuclear export of the influenza virus and identify the NXT1/NP interaction as a potential target for antiviral drug development.