Hu Yong, Liu Xiaokun, Zhang Anding, Zhou Hongbo, Liu Ziduo, Chen Huanchun, Jin Meilin
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
Cell Mol Life Sci. 2015 Mar;72(5):971-82. doi: 10.1007/s00018-014-1726-9. Epub 2014 Sep 12.
NS2 from influenza A virus mediates Crm1-dependent vRNP nuclear export through interaction with Crm1. However, even though the nuclear export signal 1 (NES1) of NS2 does not play a requisite role in NS2-Crm1 interaction, there is no doubt that NES1 is crucial for vRNP nuclear export. While the mechanism of the NES1 is still unclear, it is speculated that certain host partners might mediate the NES1 function through their interaction with NES1. In the present study, chromodomain-helicase-DNA-binding protein 3 (CHD3) was identified as a novel host nuclear protein for locating NS2 and Crm1 on dense chromatin for NS2 and Crm1-dependent vRNP nuclear export. CHD3 was confirmed to interact with NES1 in NS2, and a disruption to this interaction by mutation in NES1 significantly delayed viral vRNPs export and viral propagation. Further, the knockdown of CHD3 would affect the propagation of the wild-type virus but not the mutant with the weakened NS2-CHD3 interaction. Therefore, this study demonstrates that NES1 is required for maximal binding of NS2 to CHD3, and that the NS2-CHD3 interaction on the dense chromatin contributed to the NS2-mediated vRNP nuclear export.
甲型流感病毒的NS2通过与Crm1相互作用介导依赖Crm1的病毒核糖核蛋白（vRNP）核输出。然而，尽管NS2的核输出信号1（NES1）在NS2与Crm1的相互作用中并非必需，但毫无疑问NES1对vRNP核输出至关重要。虽然NES1的机制仍不清楚，但推测某些宿主伴侣可能通过与NES1相互作用介导其功能。在本研究中，染色质结构域解旋酶DNA结合蛋白3（CHD3）被鉴定为一种新型宿主核蛋白，可将NS2和Crm1定位在致密染色质上，以实现依赖NS2和Crm1的vRNP核输出。已证实CHD3与NS2中的NES1相互作用，NES1中的突变破坏这种相互作用会显著延迟病毒vRNP的输出和病毒传播。此外，敲低CHD3会影响野生型病毒的传播，但不会影响NS2-CHD3相互作用减弱的突变体的传播。因此，本研究表明NES1是NS2与CHD3最大程度结合所必需的，并且致密染色质上的NS2-CHD3相互作用有助于NS2介导的vRNP核输出。
