Seneca Valley Virus 3Cpro abrogates the IRF3-and IRF7-mediated innate immune response by degrading IRF3 and IRF7
Seneca Valley Virus 3Cpro abrogates the IRF3-and IRF7-mediated innate immune response by degrading IRF3 and IRF7
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DOI：
10.1016/j.virol.2018.01.028
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发表时间：
2018-05-01
期刊：
影响因子：
3.7
通讯作者：
Zheng, Haixue
中科院分区：
文献类型：
--
作者：
Xue, Qiao;Liu, Huisheng;Zheng, Haixue
塞内卡谷病毒（SVV）是一种新出现的病毒，属于小核糖核酸病毒科。对 SVV 免疫反应的基础知识有限。迄今为止，一项研究表明，SW 3C(pro) 介导宿主 MAVS、TRIF 和 TANK 在特定位点的裂解，从而逃避宿主的抗病毒先天免疫。在这项研究中，我们发现 SVV 3C(pro) 会降低 IRF3 和 IRF7 蛋白的表达水平和磷酸化。 SVV感染还会降低IRF3和IRF7蛋白的表达。 IRF3 和 IRF7 的降解取决于 3C(pro) 蛋白酶活性。我们还鉴定了 PK-15 细胞中 3C(pro) 与 IRF3 和 IRF7 之间的相互作用。详细分析表明，IRF3 和 IRF7 的降解会阻断 IFN-β、IFN-α 1、IFN-α 4 和 ISG54 的转录。总之，我们的结果证明了 SW 3C(pro) 开发的一种新机制，可以让病毒逃脱宿主的固有先天免疫系统。
Seneca Valley Virus (SVV) is a newly emerged virus belonging to the family Picornaviridae. Basic knowledge of the immunological response to SVV is limited. To date, one study has demonstrated that SW 3C(pro) mediates the cleavage of host MAVS, TRIF, and TANK at specific sites and consequently escapes the host's antiviral innate immunity. In this study, we show that SVV 3C(pro) reduces IRF3 and IRF7 protein expression level and phosphorylation. SVV infection also reduces expression of IRF3 and IRF7 protein. The degradation of IRF3 and IRF7 is dependent on the 3C(pro) protease activity. We also identify interactions between 3C(pro) and IRF3 and IRF7 in PK-15 cells. A detailed analysis revealed that the degradation of IRF3 and IRF7 blocks the transcription of IFN-beta, IFN-alpha 1, IFN-alpha 4, and ISG54. Together, our results demonstrate a novel mechanism developed by SW 3C(pro) to allow the virus to escape the host's intrinsic innate immune system.