The First Hospital of Jilin University, Institute of Virology and AIDS Research & Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130021, China.
Biomed Res Int. 2020 Feb 19;2020:2430640. doi: 10.1155/2020/2430640. eCollection 2020.
Enterovirus 71 (EV71) is the causative pathogen of hand, foot, and mouth disease (HFMD). However, no effective antiviral therapy is currently available. Some viruses could escape the host's innate immunity by upregulating suppressor of cytokine signaling (SOCS) proteins. Until now, whether EV71 evades the host immune system by regulating the expression of SOCS proteins remains unknown. In this study, we found that EV71 infection promoted SOCS expression at both mRNA and protein levels in vitro and in vivo. Consistently, the infectivity of EV71 was decreased significantly in the SOCS3 or SOCS1 knockdown cells, suggesting that SOCS1 and especially SOCS3 are crucial for EV71 infection. Further investigation showed that SOCS3 promoted virus infection by inhibiting interferon-induced STAT3 phosphorylation. SOCS1 and SOCS3 mRNA expressions were independent on virus-induced type I interferon expression but were blocked by the inhibitor of NF-B. Therefore, EV71 infection stimulates the expression of SOCS proteins in an interferon-independent way and negatively regulates the JAK/STAT signaling pathway, thus escaping host immunity. All these results may add new information to the mechanism of EV71 in fighting against type I interferon responses.
肠道病毒 71 型（EV71）是手足口病（HFMD）的病原体。然而，目前尚无有效的抗病毒治疗方法。一些病毒可以通过上调细胞因子信号转导抑制因子（SOCS）蛋白来逃避宿主的先天免疫。到目前为止，EV71 是否通过调节 SOCS 蛋白的表达来逃避宿主免疫系统仍不清楚。在本研究中，我们发现 EV71 感染在体外和体内均能促进 SOCS 蛋白在 mRNA 和蛋白水平上的表达。一致地，SOCS3 或 SOCS1 敲低细胞中 EV71 的感染性显著降低，表明 SOCS1 尤其是 SOCS3 对 EV71 感染至关重要。进一步的研究表明，SOCS3 通过抑制干扰素诱导的 STAT3 磷酸化促进病毒感染。SOCS1 和 SOCS3 的 mRNA 表达不依赖于病毒诱导的 I 型干扰素表达，但被 NF-B 抑制剂阻断。因此，EV71 感染以干扰素非依赖的方式刺激 SOCS 蛋白的表达，并负调控 JAK/STAT 信号通路，从而逃避宿主免疫。所有这些结果可能为 EV71 对抗 I 型干扰素反应的机制提供新的信息。
