Key Points FMDV 3B protein inhibits type I IFN production. FMDV 3B protein interacts with RIG-I to block RIG-I–mediated immune signaling. The aa 17A in each copy of 3B is critical for suppression of IFN response. Visual Abstract Foot-and-mouth disease is a highly contagious disease of pigs, sheep, goats, bovine, and various wild cloven-hoofed animals caused by foot-and-mouth disease virus (FMDV) that has given rise to significant economic loss to global livestock industry. FMDV 3B protein is an important determinant of virulence of the virus. Modifications in 3B protein of FMDV considerably decrease virus yield. In the current study, we demonstrated the significant role of 3B protein in suppression of type I IFN production and host antiviral response in both human embryonic kidney HEK293T cells and porcine kidney PK-15 cells. We found that 3B protein interacted with the viral RNA sensor RIG-I to block RIG-I–mediated immune signaling. 3B protein did not affect the expression of RIG-I but interacted with RIG-I to block the interaction between RIG-I and the E3 ubiquitin ligase TRIM25, which prevented the TRIM25-mediated, Lys63-linked ubiquitination and activation of RIG-I. This inhibition of RIG-I–mediated immune signaling by 3B protein decreased IFN-β, IFN-stimulated genes, and proinflammatory cytokines expression, which in turn promoted FMDV replication. All of the three nonidentical copies of 3B could inhibit type I IFN production, and the aa 17A in each copy of 3B was involved in suppression of IFN-related antiviral response during FMDV infection in porcine cells. Together, our results indicate the role of 3B in suppression of host innate immune response and reveal a novel antagonistic mechanism of FMDV that is mediated by 3B protein.

中文翻译：

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口蹄疫病毒 3B 蛋白与模式识别受体 RIG-I 相互作用以阻断 RIG-I 介导的免疫信号传导并抑制宿主抗病毒反应

要点 FMDV 3B 蛋白抑制 I 型干扰素的产生。FMDV 3B 蛋白与 RIG-I 相互作用以阻断 RIG-I 介导的免疫信号传导。3B 的每个副本中的 aa 17A 对抑制 IFN 反应至关重要。视觉摘要 口蹄疫是由口蹄疫病毒（FMDV）引起的猪、绵羊、山羊、牛和各种野生偶蹄动物的一种高度接触性传染病，给猪、绵羊、山羊、牛和各种野生偶蹄动物造成了严重的经济损失。全球畜牧业。FMDV 3B 蛋白是病毒毒力的重要决定因素。FMDV 3B 蛋白的修饰显着降低病毒产量。在目前的研究中，我们证明了 3B 蛋白在抑制人胚胎肾 HEK293T 细胞和猪肾 PK-15 细胞中 I 型 IFN 产生和宿主抗病毒反应中的重要作用。我们发现 3B 蛋白与病毒 RNA 传感器 RIG-I 相互作用以阻断 RIG-I 介导的免疫信号传导。3B 蛋白不影响 RIG-I 的表达，但与 RIG-I 相互作用以阻断 RIG-I 与 E3 泛素连接酶 TRIM25 之间的相互作用，从而阻止了 TRIM25 介导的、Lys63 连接的泛素化和 RIG-I 的激活。3B 蛋白对 RIG-I 介导的免疫信号的抑制降低了 IFN-β、IFN 刺激基因和促炎细胞因子的表达，进而促进了 FMDV 的复制。3B 的所有三个不同拷贝都可以抑制 I 型 IFN 的产生，并且每个 3B 拷贝中的 aa 17A 参与抑制猪细胞中 FMDV 感染期间 IFN 相关的抗病毒反应。一起，