Li Weiwei, Zhu Zixiang, Cao Weijun, Yang Fan, Zhang Xiangle, Li Dan, Zhang Keshan, Li Pengfei, Mao Ruoqing, Liu Xiangtao, Zheng Haixue
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China.
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China.
Mol Immunol. 2016 Jul;75:112-21. doi: 10.1016/j.molimm.2016.05.016. Epub 2016 Jun 3.
The enzymatic activities of esterase D (ESD) are involved in many human diseases. However, no antiviral property of ESD has been described to date. Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease. In this study, we showed that FMDV infection triggered ESD expression. Overexpression of ESD significantly suppressed FMDV replication and knockdown of ESD expression enhanced virus replication, showing an essential antiviral role of ESD. Furthermore, we found that Sendai-virus-induced interferon (IFN) signaling was enhanced by upregulation of ESD, and ESD promoted activation of the IFN-β promoter simulated by IFN regulatory factor (IRF)3 or its upstream molecules (retinoic acid-inducible gene-I, melanoma differentiation-associated protein 5, virus-induced signaling adaptor and TANK binding kinase 1). Detailed analysis revealed that ESD protein enhanced IRF3 phosphorylation during FMDV infection. Overexpression of ESD also promoted the expression of various antiviral interferon-stimulated genes (ISGs) and knockdown of ESD impaired the expression of these antiviral genes during FMDV infection. Our findings demonstrate a new mechanism evolved by ESD to enhance type I IFN signal transduction and suppress viral replication during FMDV infection.
酯酶D（ESD）的酶活性与多种人类疾病有关。然而，迄今为止尚未有ESD抗病毒特性的相关描述。口蹄疫病毒（FMDV）是口蹄疫的病原体。在本研究中，我们发现FMDV感染会引发ESD表达。ESD的过表达显著抑制FMDV复制，而敲低ESD表达则增强病毒复制，这表明ESD具有重要的抗病毒作用。此外，我们发现上调ESD可增强仙台病毒诱导的干扰素（IFN）信号传导，并且ESD可促进由IFN调节因子（IRF）3或其上游分子（视黄酸诱导基因I、黑色素瘤分化相关蛋白5、病毒诱导信号衔接子和TANK结合激酶1）模拟的IFN-β启动子的激活。详细分析表明，在FMDV感染期间，ESD蛋白增强了IRF3的磷酸化。ESD的过表达还促进了多种抗病毒干扰素刺激基因（ISG）的表达，而敲低ESD则会损害FMDV感染期间这些抗病毒基因的表达。我们的研究结果揭示了ESD在FMDV感染期间增强I型IFN信号转导并抑制病毒复制的新机制。
