gga-miR-9*inhibits IFN production in antiviral innate immunity by targeting interferon regulatory factor 2 to promote IBDV replication
gga-miR-9*inhibits IFN production in antiviral innate immunity by targeting interferon regulatory factor 2 to promote IBDV replication
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DOI：
10.1016/j.vetmic.2015.04.023
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发表时间：
2015-07-09
影响因子：
3.3
通讯作者：
Zhang, Hai-bin
中科院分区：
文献类型：
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作者：
Ouyang, Wei;Wang, Yong-shan;Zhang, Hai-bin
微小RNA（miRNAs）是在病毒感染期间参与宿主-病原体相互作用的小的非编码RNA。在目前的研究中，miRNA分析显示，一组microRNA，包括gga-miR-9*，在感染传染性法氏囊病病毒（IBDV）后，在无特异性病原体（SPF）鸡中显著上调;然而，gga-miR-9* 在病毒感染期间的生物学功能仍然未知。使用TCID 50测定，发现gga-miR-9* 的异位表达显著促进IBDV复制。反过来，gga-miR-9* 负调节IBDV触发的I型IFN产生，从而促进DF-1细胞中的IBDV复制。生物信息学分析表明，干扰素调节因子2（interferon regulatory factor 2，IRF 2）的3'非翻译区（untranslated region，UTR）有两个gga-miR-9* 的结合位点。通过荧光素酶测定确定gga-miR-9* 对IRF 2 3 'UTR的靶向。使用gga-miR-9* 模拟物功能性过表达gga-miR-9*，抑制IRF 2 mRNA和蛋白表达。gga-miR-9* 抑制剂的转染消除了IRF 2蛋白表达的抑制。此外，IRF 2敲低介导了gga-miR-9* 对I型IFN介导的抗病毒应答的增强作用。这些发现表明，诱导型gga-miR-9* 反馈通过靶向IRF 2抑制I型IFN产生来负调节宿主抗病毒先天免疫应答。(C)2015 Elsevier B. V.版权所有。
MicroRNAs (miRNAs) are small non-coding RNAs that contribute to the repertoire of host-pathogen interactions during viral infections. In the current study, miRNA analysis showed that a panel of microRNAs, including gga-miR-9*, were markedly upregulated in specific-pathogen-free (SPF) chickens upon infection with infectious bursal disease virus (IBDV); however, the biological function of gga-miR-9* during viral infection remains unknown. Using a TCID50 assay, it was found that ectopic expression of gga-miR-9* significantly promoted IBDV replication. In turn, gga-miR-9* negatively regulated IBDV-triggered type I IFN production, thus promoting IBDV replication in DF-1 cells. Bioinformatics analysis indicates that the 3' untranslated region (UTR) of interferon regulatory factor 2 (IRF2) has two putative binding sites for gga-miR-9*. Targeting of IRF2 3'UTR by gga-miR-9* was determined by luciferase assay. Functional overexpression of gga-miR-9*, using gga-miR-9* mimics, inhibited IRF2 mRNA and protein expression. Transfection of the gga-miR-9* inhibitor abolished the suppression of IRF2 protein expression. Furthermore, IRF2 knockdown mediated the enhancing effect of gga-miR-9* on the type I IFN-mediated antiviral response. These findings indicate that inducible gga-miR-9* feedback negatively regulates the host antiviral innate immune response by suppressing type I IFN production via targeting IRF2. (C) 2015 Elsevier B.V. All rights reserved.