Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects
Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects
复制标题
肠道病毒 71 抑制白细胞介素增强子结合因子 2 的产生和细胞核易位，以拮抗 ILF2 的抗病毒作用。
DOI：
10.3390/v12010022
复制
发表时间：
2020-01-01
期刊：
影响因子：
4.7
通讯作者：
Wu, Jianguo
中科院分区：
文献类型：
--
作者：
Jin, Jing;Wang, Wenbiao;Wu, Jianguo
肠病毒71型（EV 71）感染可导致手足口病、脑膜脑炎、新生儿败血症，甚至儿童致命性脑炎，从而对公共卫生构成严重威胁。确定EV 71感染的潜在调节机制是重要的。在这项研究中，我们初步表明，白细胞介素增强子结合因子2（ILF 2）减少EV 71的50%组织培养感染剂量（TCID 50）和衰减EV 71空斑形成单位（PFU），从而抑制EV 71感染。微阵列数据分析显示，EV 71感染后ILF 2 mRNA减少。细胞研究表明，EV 71感染抑制ILF 2 mRNA的表达和蛋白质的生产在人白血病单核细胞（THP-1）分化的巨噬细胞和人横纹肌肉瘤（RD）细胞。此外，EV 71非结构蛋白2B在人胚肾（HEK 293 T）细胞中与ILF 2相互作用。有趣的是，在EV 71 2B存在下，ILF 2从细胞核易位到细胞质，并且它与2B共定位在细胞质中。因此，我们提出了一个独特的机制，EV 71拮抗ILF 2介导的抗病毒作用，通过抑制ILF 2的表达和促进ILF 2从细胞核易位到细胞质通过其2B蛋白。
Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.