Identification of cellular microRNA-136 as a dual regulator of RIG-I-mediated innate immunity that antagonizes H5N1 IAV replication in A549 cells.
Identification of cellular microRNA-136 as a dual regulator of RIG-I-mediated innate immunity that antagonizes H5N1 IAV replication in A549 cells.
复制标题
鉴定细胞 microRNA-136 作为 RIG-I 介导的先天免疫的双重调节剂，拮抗 A549 细胞中的 H5N1 IAV 复制
DOI：
10.1038/srep14991
复制
发表时间：
2015-10-09
影响因子：
4.6
通讯作者：
Jin M
中科院分区：
文献类型：
--
作者：
Zhao L;Zhu J;Zhou H;Zhao Z;Zou Z;Liu X;Lin X;Zhang X;Deng X;Wang R;Chen H;Jin M
H5N1 甲型流感病毒 (IAV) 会导致动物和人类严重的呼吸道疾病和高死亡率。人们正在越来越多地研究 MicroRNA，以评估其作为对抗病毒感染的治疗实体的潜力。然而，描述 microRNA 在调节宿主与 H5N1 病毒相互作用中的作用的机制研究仍然很少。在这里，我们使用感染高致病性禽流感病毒的 A549 人肺上皮细胞进行 microRNA 微阵列分析。受感染细胞的 microRNA 表达谱发现，少数 microRNA 在 H5N1 甲型流感病毒感染后失调。在差异表达的 microRNA 中，miR-136 上调了 5 倍，并且在体外对 H5N1 甲型流感病毒和水泡性口炎病毒表现出有效的抗病毒活性。一方面，3'非翻译区（UTR）报告基因分析揭示了 IL-6 3'UTR 中的 miR-136 结合位点。然而，另一方面，我们随后确定miR-136同时充当视黄酸诱导基因1（RIG-I）的免疫激动剂，从而导致A549细胞中IL-6和IFN-β的积累。总体而言，这项研究暗示了 miRNA-136 在调节宿主抗病毒先天免疫中的双重作用，并表明 microRNA 激活途径通过模式识别受体在病毒感染中发挥着重要作用。
H5N1 influenza A virus (IAV) causes severe respiratory diseases and high mortality rates in animals and humans. MicroRNAs are being increasingly studied to evaluate their potential as therapeutic entities to combat viral infection. However, mechanistic studies delineating the roles of microRNAs in regulating host-H5N1 virus interactions remain scarce. Here, we performed microRNA microarray analysis using A549 human lung epithelial cells infected with a highly pathogenic avian influenza virus. The microRNA expression profile of infected cells identified a small number of microRNAs being dysregulated upon H5N1 influenza A virus infection. Of the differentially expressed microRNAs, miR-136 was up-regulated 5-fold and exhibited potent antiviral activityin vitroagainst H5N1 influenza A virus, as well as vesicular stomatitis virus. On the one hand, 3′-untranslated region (UTR) reporter analysis revealed a miR-136 binding site in the 3′ UTR of IL-6. However, on the other hand, we subsequently determined that miR-136 meanwhile acts as an immune agonist of retinoic acid-inducible gene 1 (RIG-I), thereby causing IL-6 and IFN-β accumulation in A549 cells. Overall, this study implicates the dual role of miRNA-136 in the regulation of host antiviral innate immunity and suggests an important role for the microRNA-activated pathway in viral infection via pattern recognition receptors.