Threonine 80 phosphorylation of non-structural protein 1 regulates the replication of influenza A virus by reducing the binding affinity with RIG-I
Threonine 80 phosphorylation of non-structural protein 1 regulates the replication of influenza A virus by reducing the binding affinity with RIG-I
复制标题
非结构蛋白1的苏氨酸80磷酸化通过降低与RIG-I的结合亲和力调节甲型流感病毒的复制
DOI：
10.1111/cmi.12643
复制
发表时间：
2017
影响因子：
3.4
通讯作者：
Liu Wenjun
中科院分区：
文献类型：
--
作者：
Zheng Weinan;Cao Shuaishuai;Chen Can;Li Jing;Zhang Shuang;Jiang Jingwen;Niu Yange;Fan Wenhui;Li Yun;Bi Yuhai;Gao George F.;Sun Lei;Liu Wenjun
甲型流感病毒通过其非结构蛋白1 （NS1）劫持先天免疫来逃避宿主的抗病毒防御。通过质谱分析，发现苏氨酸80 （T80）是流感病毒a /WSN/1933(H1N1) NS1中一个新的磷酸化残基。通过产生编码NS1 T80突变体的重组流感病毒，研究了该磷酸化位点在病毒复制过程中的作用。T80E（拟磷）突变体能减弱病毒复制，而T80A（非磷酸化）突变体则不能。在小鼠模型实验中观察到这些突变体的相似表型。在进一步的研究中，T80E突变体降低了NS1与病毒核蛋白（NP）的结合能力，导致病毒核糖核蛋白（vRNP）介导的病毒转录受损。T80E突变体也不能通过降低NS1与维甲酸诱导的基因1蛋白（RIG - I）之间的结合亲和力来抑制干扰素（IFN）的产生，从而导致病毒复制的衰减。综上所述，本研究表明NS1的T80磷酸化通过控制RIG - I介导的IFN产生和vRNP活性来减少流感病毒的复制。
Influenza A virus evades host antiviral defense through hijacking innate immunity by its non‐structural protein 1 (NS1). By using mass spectrometry, threonine 80 (T80) was identified as a novel phosphorylated residue in the NS1 of the influenza virus A/WSN/1933(H1N1). By generating recombinant influenza viruses encoding NS1 T80 mutants, the roles of this phosphorylation site were characterized during viral replication. The T80E (phosphomimetic) mutant attenuated virus replication, whereas the T80A (non‐phosphorylatable) mutant did not. Similar phenotypes were observed for these mutants in a mouse model experiment. In further study, the T80E mutant decreased the binding capacity between NS1 and viral nucleoprotein (NP), leading to impaired viral ribonucleoprotein (vRNP)‐mediated viral transcription. The T80E mutant was also unable to inhibit interferon (IFN) production by reducing the binding affinity between NS1 and retinoic acid‐induced gene 1 protein (RIG‐I), causing attenuation of virus replication. Taken together, the present study reveals that T80 phosphorylation of NS1 reduced influenza virus replication through controlling RIG‐I‐mediated IFN production and vRNP activity.