Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Pathogenic Biology and Immunology, School of Basic Medical Science, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2019 Dec 11;10:2810. doi: 10.3389/fimmu.2019.02810. eCollection 2019.
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.
Viperin 是一种干扰素诱导蛋白，负责对各种不同病毒产生多种抗病毒反应。我们之前的研究表明，单纯疱疹病毒 1（HSV-1）的核糖核酸酶 UL41 可以降解 viperin 的 mRNA，从而促进 HSV-1 的复制。然而，目前尚不清楚 HSV-1 编码的其他蛋白是否可以调节 viperin 的功能。在这里，我们鉴定到一个新的 viperin 相关蛋白，糖蛋白 D（gD）。为了验证 gD 与 viperin 之间的相互作用，首先将 gD 和 viperin 表达质粒共转染到 COS-7 细胞中，荧光显微镜显示它们在核周区域共定位，然后通过共免疫沉淀（Co-IP）实验进一步证实了这种潜在的相互作用。此外，共聚焦显微镜显示 gD 和 viperin 共定位于高尔基体和脂滴。进一步的双荧光素酶报告基因和 Co-IP 实验表明，gD 和 viperin 的相互作用通过促进 viperin 和 IRAK1 的相互作用以及促进 K63 连接的 IRAK1 多泛素化，导致 IRF7 介导的 IFN-β 表达增加。然而，gD 通过减少 viperin 和 TRAF6 的相互作用抑制了 TRAF6 诱导的 NF-κB 活性。此外，gD 抑制了 viperin 介导的 IRAK1 和 TRAF6 之间的相互作用。最终，gD 和 viperin 的相互作用被证实可显著抑制 HSV-1 的增殖。总之，这项研究为阐明 gD 和 viperin 在 HSV-1 复制周期中的功能和生理意义开辟了新的途径。
