Enterovirus 71 antagonizes the antiviral activity of host STAT3 and IL-6R with partial dependence on virus-induced miR-124
Enterovirus 71 antagonizes the antiviral activity of host STAT3 and IL-6R with partial dependence on virus-induced miR-124
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肠道病毒 71 拮抗宿主 STAT3 和 IL-6R 的抗病毒活性，部分依赖于病毒诱导的 miR-124。
DOI：
10.1099/jgv.0.000967
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发表时间：
2017-12-01
影响因子：
3.8
通讯作者：
Long, Jian-Er
中科院分区：
文献类型：
--
作者：
Chang, Zhangmei;Wang, Yan;Long, Jian-Er
肠病毒71型（EV 71）引起了手足口病的大规模爆发。EV 71感染增加许多宿主细胞因子和促炎因子的产生，包括白细胞介素（IL）-6、IL-10和考克斯-2。这些分子中的一些可以刺激信号转导子和转录激活子3（STAT 3），其在调节宿主免疫应答和一些病毒性疾病中起关键作用。然而，STAT 3在EV 71感染中的作用仍然未知。本研究发现STAT 3（pY 705-STAT 3）的磷酸化水平与EV 71感染密切相关。进一步的实验表明，STAT 3发挥抗EV 71活性。然而，STAT 3的抗病毒活性被EV 71诱导的miR-124部分拮抗，miR-124直接靶向STAT 3 mRNA。类似地，IL-6受体复合物的α亚基IL-6 R表现出抗EV 71活性，并被病毒诱导的miR-124直接靶向。这些结果表明EV 71可以通过EV 71诱导的miR-124逃避宿主IL-6 R和STAT 3介导的抗病毒活性。这表明控制miR-124及其下游靶点IL-6 R和STAT 3可能有利于EV 71感染的抗病毒治疗。
Enterovirus 71 (EV71) has caused major outbreaks of hand, foot and mouth disease. EV71 infections increase the production of many host cytokines and pro-inflammatory factors, including interleukin (IL)-6, IL-10 and COX-2. Some of these molecules could stimulate the signal transducer and activator of transcription 3 (STAT3), which plays a key role in regulating host immune responses and several viral diseases. However, the role of STAT3 in EV71 infection remains unknown. This study found that the phosphorylation levels of STAT3 (pY705-STAT3) are closely related to EV71 infection. Further experiments revealed that STAT3 exerts an anti-EV71 activity. However, the antiviral activity of STAT3 is partially antagonized by EV71-induced miR-124, which directly targets STAT3 mRNA. Similarly, IL-6R, the α-subunit of the IL-6 receptor complex, exhibits anti-EV71 activity and is directly targeted by the virus-induced miR-124. These results indicate that EV71 can evade host IL-6R- and STAT3-mediated antiviral activities by EV71-induced miR-124. This suggests that controlling miR-124 and the downstream targets, IL-6R and STAT3, might benefit the antiviral treatment of EV71 infection.