EV71 Infection Induces IFNβ Expression in Neural Cells
EV71 Infection Induces IFNβ Expression in Neural Cells
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DOI：
10.3390/v11121121
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发表时间：
2019-12-01
期刊：
影响因子：
4.7
通讯作者：
Chen, Sheng-Hung
中科院分区：
文献类型：
--
作者：
Huang, Hsing-, I;Lin, Jhao-Yin;Chen, Sheng-Hung
肠病毒71型（EV71）可侵入中枢神经系统，引起神经系统疾病。越来越多的证据表明，EV71可以直接感染中枢神经系统的神经元。已知中枢神经系统的先天免疫反应在限制病原体感染中起重要作用。因此，研究EV71对神经细胞感染的影响对了解疾病发病机制具有重要意义。本研究用EV71感染人神经细胞，检测干扰素β (IFN β)的表达。我们的研究结果表明，在ev71感染的神经细胞中，IFN β的表达通过模式识别受体（PRRs）感知病毒RNA而上调。发现PRRs toll样受体3 （TLR3）、toll样受体8 （TLR8）和黑色素瘤分化相关基因5 (MDA-5)，但不包括视黄酸诱导基因i （RIG-I）和toll样受体7 (TLR7)，可介导ev71介导的IFN β诱导。尽管病毒蛋白在神经细胞中表现出切割线粒体抗病毒信号蛋白（MAVS）和含有Toll/IL-1受体（TIR）结构域的适配器诱导ifn - β (TRIF)的能力，但这些细胞中的病毒蛋白表达水平较低。此外，神经细胞在EV71 vRNA刺激下有效地产生IFN β转录物。用抗干扰素β抗体处理感染细胞导致病毒复制增加，表明干扰素β释放可能在限制病毒生长方面发挥作用。这些结果表明EV71感染可通过PRR途径诱导神经细胞中IFN β的表达。
Enterovirus 71 (EV71) can invade the central nervous system (CNS) and cause neurological disease. Accumulating evidence indicates that EV71 can directly infect neurons in the CNS. Innate immune responses in the CNS have been known to play an essential role in limiting pathogen infections. Thus, investigating the effects of EV71 infection of neural cells is important for understanding disease pathogenesis. In this study, human neural cells were infected with EV71, and interferon beta (IFN beta) expression was examined. Our results show that IFN beta expression was upregulated in EV71-infected neural cells via pattern recognition receptors (PRRs) sensing of virus RNA. The PRRs Toll-like receptor 3 (TLR3), Toll-like receptor 8 (TLR8), and melanoma differentiation-associated gene-5 (MDA-5), but not retinoic acid-inducible gene-I (RIG-I) and Toll-like receptor 7 (TLR7), were found to be EV71-mediated IFN beta induction. Although viral proteins exhibited the ability to cleave mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-beta (TRIF) in neural cells, levels of viral protein expression were low in these cells. Furthermore, neural cells efficiently produced IFN beta transcripts upon EV71 vRNA stimulation. Treating infected cells with anti-IFN beta antibodies resulted in increased virus replication, indicating that IFN beta release may play a role in limiting viral growth. These results indicate that EV71 infection can induce IFN beta expression in neural cells through PRR pathways.