Threonine 80 Phosphorylation of Non-Structural Protein NS1 Regulates the Replication of Influenza A Virus by Reducing the Binding Affinity with RIG-I----中国科学院微生物研究所

科研成果

论文题目:	Threonine 80 Phosphorylation of Non-Structural Protein NS1 Regulates the Replication of Influenza A Virus by Reducing the Binding Affinity with RIG-I
作者:	Zheng Weinan, Cao Shuaishuai, Chen Can, Li Jing, Zhang Shuang, Jiang Jingwen, Niu Yange, Fan Wenhui, Li Yun, Bi Yuhai, Sun Lei, Gao George F, and Liu Wenjun.
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刊物名称:	Cell Microbiol
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年份:	2016
影响因子:	4.541
论文下载:	http://onlinelibrary.wiley.com/doi/10.1111/cmi.12643/abstract;jsessionid=BC9BC92278E29B53CA3D96265442C315.f03t04
摘要:	Influenza A virus evades host antiviral defense through hijacking innate immunity by its nonstructural 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 experiments. 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 RNA 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.