The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-β signaling pathway
The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-β signaling pathway
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口蹄疫病毒VP3结构蛋白抑制IFN-β信号通路
DOI：
10.1096/fj.15-281410
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发表时间：
2016-05-01
期刊：
影响因子：
4.8
通讯作者：
Shu, Hongbing
中科院分区：
文献类型：
--
作者：
Li, Dan;Yang, Wenping;Shu, Hongbing
口蹄疫是由口蹄疫病毒（Foot-and-mouth virus，FMDV）感染引起的偶蹄类动物的一种常见病。FMDV通过表达拮抗细胞先天免疫的蛋白质，如前导蛋白酶和3C蛋白酶，来规避I型IFN应答。我们鉴定了FMDV结构蛋白VP 3作为病毒触发的IFN-β信号通路的负调节因子。FMDV VP 3的表达抑制仙台病毒触发的IFN调节因子3的激活和视黄酸诱导基因I/黑色素瘤分化相关蛋白5的表达。瞬时转染和免疫共沉淀证实，结构蛋白VP 3与病毒诱导的信号转导接头（VISA）相互作用，这是依赖于VP 3的C-末端氨基酸111-220。此外，我们发现FMDV VP 3通过破坏VISA的mRNA来抑制VISA的表达。总之，我们的研究结果揭示了FMDV结构VP 3蛋白逃避宿主先天免疫的新策略。Li，D.，杨伟，杨，F.，刘洪，Zhu，Z.，Lian，K.，雷，C.，Li，S.，刘，X.，郑洪，Shu，H.口蹄疫病毒VP 3结构蛋白抑制IFN-β信号通路。
Foot-and-mouth disease is a frequently occurring disease of cloven-hoofed animals that is caused by infection with the foot-and-mouth virus (FMDV). FMDV circumvents the type-I IFN response by expressing proteins that antagonize cellular innate immunity, such as leader protease and 3C protease. We identified the FMDV structural protein VP3 as a negative regulator of the virus-triggered IFN-beta signaling pathway. Expression of FMDV VP3 inhibited the Sendai virus-triggered activation of IFN regulatory factor-3 and the expression of retinoic acid-inducible gene-I/melanoma differentiation-associated protein-5. Transient transfection and coimmunoprecipitation confirmed that the structural protein VP3 interacts with virus-induced signaling adapter (VISA), which is dependent on the C-terminal aa 111-220 of VP3. In addition, we found that FMDV VP3 inhibits the expression of VISA by disrupting its mRNA. Taken together, our findings reveal a novel strategy used by the structural VP3 protein of FMDV to evade host innate immunity.-Li, D., Yang, W., Yang, F., Liu, H., Zhu, Z., Lian, K., Lei, C., Li, S., Liu, X., Zheng, H., Shu, H. The VP3 structural protein of foot-andmouth disease virus inhibits the IFN-beta signaling pathway.