Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway.
Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway.
复制标题
口蹄疫病毒非结构蛋白 3A 抑制干扰素-β 信号通路。
DOI：
10.1038/srep21888
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发表时间：
2016-02-17
影响因子：
4.6
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Li D;Lei C;Xu Z;Yang F;Liu H;Zhu Z;Li S;Liu X;Shu H;Zheng H
口蹄疫病毒（Foot-and-mouth disease virus，FMDV）是口蹄疫的病原体，主要危害偶蹄类动物。口蹄疫病毒的病理生理机制尚未完全清楚，其对宿主天然免疫系统的逃避机制也不清楚。在此，FMDV非结构蛋白3A被鉴定为病毒触发的IFN-β信号通路的负调节剂。FMDV 3A的过表达抑制仙台病毒触发的IRF 3的激活和RIG-I/MDA 5的表达。瞬时转染和免疫共沉淀实验表明，FMDV 3A与RIG-1、MDA 5和VISA相互作用依赖于3A的N端51个氨基酸。此外，3A还通过破坏它们的mRNA水平来抑制RIG-I、MDA 5和VISA的表达。这些结果表明3A抑制了RLR介导的IFN-β诱导，并揭示了FMDV 3A蛋白逃避宿主先天免疫系统的新机制。
Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system.