MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction
MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction
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MicroRNA-302a 抑制甲型流感病毒刺激的干扰素调节因子 5 表达和细胞因子风暴诱导
DOI：
10.1074/jbc.m117.805937
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发表时间：
2017-12-29
影响因子：
4.8
通讯作者：
Liu, Shi
中科院分区：
文献类型：
--
作者：
Chen, Xueyuan;Zhou, Li;Liu, Shi
在甲型流感病毒（IAV）感染期间，细胞因子风暴在临床结果中起着至关重要的作用。我们以前报道过microRNA（miR）-302 c通过靶向核因子B（NF-B）诱导激酶的3-UTR来调节IAV诱导的IFN表达。在目前的研究中，我们发现miR-302簇的另一个成员miR-302 a控制IAV诱导的细胞因子风暴。根据基于细胞和基因敲除小鼠模型的结果，IAV通过干扰素调节因子-5（IRF-5）诱导细胞因子风暴。我们还发现，IAV感染上调IRF-5的表达，IRF-5反过来促进IAV复制。此外，我们观察到IRF-5是miR-302 a的直接靶点，miR-302 a通过结合其3-UTR下调IRF-5的表达。此外，IAV通过下调miR-302 a的表达来增加IRF-5的表达。有趣的是，miR-302 a抑制IAV复制。在IAV感染患者中，miR-302 a表达下调，而IRF-5表达上调。总之，我们的工作揭示和定义了一个信号通路牵连在IAV诱导的细胞因子风暴。
During influenza A virus (IAV) infection, cytokine storms play a vital and critical role in clinical outcomes. We have previously reported that microRNA (miR)-302c regulates IAV-induced IFN expression by targeting the 3-UTR of nuclear factor B (NF-B)-inducing kinase. In the current study, we found that miR-302a, another member of the miR-302 cluster, controls the IAV-induced cytokine storm. According to results from cell-based and knockout mouse models, IAV induces a cytokine storm via interferon regulatory factor-5 (IRF-5). We also found that IAV infection up-regulates IRF-5 expression and that IRF-5 in turn promotes IAV replication. Furthermore, we observed that IRF-5 is a direct target of miR-302a, which down-regulated IRF-5 expression by binding its 3-UTR. Moreover, IAV increased IRF-5 expression by down-regulating miR-302a expression. Interestingly, miR-302a inhibited IAV replication. In IAV-infected patients, miR-302a expression was down-regulated, whereas IRF-5 expression was up-regulated. Taken together, our work uncovers and defines a signaling pathway implicated in an IAV-induced cytokine storm.