The Interaction Mechanism Between Herpes Simplex Virus 1 Glycoprotein D and Host Antiviral Protein Viperin
The Interaction Mechanism Between Herpes Simplex Virus 1 Glycoprotein D and Host Antiviral Protein Viperin
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单纯疱疹病毒1型糖蛋白D与宿主抗病毒蛋白Viperin的相互作用机制
DOI：
10.3389/fimmu.2019.02810
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发表时间：
2019-12-11
影响因子：
7.3
通讯作者：
Cai, Mingsheng
中科院分区：
文献类型：
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作者：
Li, Meili;Liao, Zongmin;Cai, Mingsheng
维珀林（Viperin）是一种干扰素诱导蛋白，负责对不同病毒产生多种抗病毒反应。我们先前的研究表明，单纯疱疹病毒1型（HSV - 1）的核糖核酸酶UL41能够降解维珀林的mRNA以促进HSV - 1的复制。然而，尚不清楚其他HSV - 1编码的蛋白质是否能够调节维珀林的功能。在此，一种新的与维珀林相关的蛋白质——糖蛋白D（gD）被鉴定出来。为了验证gD和维珀林之间的相互作用，首先将gD和维珀林表达质粒共转染到COS - 7细胞中，荧光显微镜显示它们共定位在核周区域，然后通过免疫共沉淀（Co - IP）试验证实了这种潜在的相互作用。此外，共聚焦显微镜显示gD和维珀林共定位在高尔基体和脂滴处。进一步地，双荧光素酶报告基因和免疫共沉淀试验表明，gD和维珀林的相互作用通过促进维珀林与IRAK1的相互作用以及促进K63连接的IRAK1多聚泛素化，导致IRF7介导的IFN - β表达增加。然而，gD通过降低维珀林与TRAF6的相互作用抑制了TRAF6诱导的NF - κB活性。此外，gD抑制了维珀林介导的IRAK1与TRAF6之间的相互作用。最终，gD和维珀林的相互作用被证实能够显著抑制HSV - 1的增殖。总之，这项研究将为阐明gD和维珀林在HSV - 1复制周期中的功能和生理意义开辟新的途径。
Viperin is an interferon-inducible protein that responsible for a variety of antiviral responses to different viruses. Our previous study has shown that the ribonuclease UL41 of herpes simplex virus 1 (HSV-1) can degrade the mRNA of viperin to promote HSV-1 replication. However, it is not clear whether other HSV-1 encoded proteins can regulate the function of viperin. Here, one novel viperin associated protein, glycoprotein D (gD), was identified. To verify the interaction between gD and viperin, gD and viperin expression plasmids were firstly co-transfected into COS-7 cells, and fluorescence microscope showed they co-localized at the perinuclear region, then this potential interaction was confirmed by co-immunoprecipitation (Co-IP) assays. Moreover, confocal microscopy demonstrated that gD and viperin co-localized at the Golgi body and lipid droplets. Furthermore, dual-luciferase reporter and Co-IP assays showed gD and viperin interaction leaded to the increase of IRF7-mediated IFN-β expression through promoting viperin and IRAK1 interaction and facilitating K63-linked IRAK1 polyubiquitination. Nevertheless, gD inhibited TRAF6-induced NF-κB activity by decreasing the interaction of viperin and TRAF6. In addition, gD restrained viperin-mediated interaction between IRAK1 and TRAF6. Eventually, gD and viperin interaction was corroborated to significantly inhibit the proliferation of HSV-1. Taken together, this study would open up new avenues toward delineating the function and physiological significance of gD and viperin during HSV-1 replication cycle.