Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication
Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication
复制标题
酯酶 D 增强 I 型干扰素信号转导，抑制口蹄疫病毒复制。
DOI：
10.1016/j.molimm.2016.05.016
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发表时间：
2016-07-01
影响因子：
3.6
通讯作者：
Zheng, Haixue
中科院分区：
文献类型：
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作者：
Li, Weiwei;Zhu, Zixiang;Zheng, Haixue
酯酶D （ESD）的酶活性与许多人类疾病有关。然而，到目前为止，还没有关于ESD抗病毒特性的报道。口蹄疫病毒（FMDV）是口蹄疫的病原。在本研究中，我们发现FMDV感染触发了ESD表达。过表达ESD可显著抑制FMDV的复制，而敲低ESD表达可增强病毒复制，显示ESD具有重要的抗病毒作用。此外，我们发现仙台病毒诱导的干扰素（IFN）信号通过ESD的上调而增强，ESD促进了IFN调节因子（IRF）3或其上游分子（视黄酸诱导基因- 1、黑色素瘤分化相关蛋白5、病毒诱导的信号转接器和TANK结合激酶1）模拟的IFN- β启动子的激活。详细分析显示，在FMDV感染过程中，ESD蛋白增强了IRF3磷酸化。过表达ESD也促进了多种抗病毒干扰素刺激基因（ISGs）的表达，而在FMDV感染过程中，敲低ESD会损害这些抗病毒基因的表达。我们的研究结果表明，在FMDV感染过程中，ESD进化出一种新的机制来增强I型IFN信号转导并抑制病毒复制。(C) 2016 Elsevier Ltd.版权所有。
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. Over expression 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-beta 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. (C) 2016 Elsevier Ltd. All rights reserved.