gga-miR-2127 downregulates the translation of chicken p53 and attenuates chp53-mediated innate immune response against IBDV infection
gga-miR-2127 downregulates the translation of chicken p53 and attenuates chp53-mediated innate immune response against IBDV infection
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gga-miR-2127 下调鸡 p53 的翻译并减弱 chp53 介导的针对 IBDV 感染的先天免疫反应
DOI：
10.1016/j.vetmic.2016.12.007
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发表时间：
2017-01-01
影响因子：
3.3
通讯作者：
Luo, Kai
中科院分区：
文献类型：
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作者：
Ouyang, Wei;Wang, Yong-shan;Luo, Kai
传染性法氏囊病（IBD）以感染禽类的免疫抑制为特征。IBD病毒（IBDV）抑制宿主免疫系统的分子机制仍有待阐明。肿瘤抑制蛋白p53可以抑制多种病毒的复制，但其对IBDV的作用尚不清楚。本研究建立了鸡胚成纤维细胞系DF-1细胞体外感染模型，探讨鸡p53 （chp53）对IBDV感染的抗病毒作用。在ibdv感染的DF-1细胞中，chp53的表达水平和活性显著升高。chp53的过表达抑制了IBDV的复制，上调了多种鸡抗病毒先天免疫基因（IPS-1、IRF3、PKR、OAS和Mx）的表达，而chp53的抑制则导致相反的效果。这表明chp53激活了鸡对IBDV感染的抗病毒先天免疫反应。生物信息学分析和双荧光素酶报告基因检测显示，gga-miR-2127靶向chp53的3'UTR。qRT-PCR和western blot结果显示，gga-miR-2127在DF-1细胞中过表达，不仅能下调鸡体内chp53和抗病毒先天免疫基因的表达水平，还能促进IBDV的复制。我们的研究结果表明，gga-miR-2127通过靶向chp53的3'UTR下调chp53 mRNA的翻译，并减弱chp53介导的针对IBDV的抗病毒先天免疫反应。(C) 2016 Elsevier B.V.版权所有
Infectious bursal disease (IBD) is characterized by the immune suppression of infected birds. The molecular mechanism by which IBD virus (IBDV) suppresses the host immune system remains to be elucidated. The tumor suppressor protein p53 can inhibit the replication of various viruses, but its effect on IBDV remains unknown. This study established an in vitro infection model based on DF-1 cells (chicken embryo fibroblast cell line) to investigate the antiviral effects of chicken p53 (chp53) on IBDV infection. The expression level and activity of chp53 remarkably increased in IBDV-infected DF-1 cells. The overexpression of chp53 inhibited IBDV replication and upregulated the expression of multiple chicken antiviral innate immunity genes (IPS-1, IRF3, PKR, OAS, and Mx), whereas the suppression of chp53 led to the opposite effect. This result indicates that chp53 activates the antiviral innate immune response of chickens to IBDV infection. Bioinformatics analysis and dual-luciferase reporter assay showed that gga-miR-2127 targeted the 3'UTR of chp53. qRT-PCR and western blot revealed that gga-miR-2127 overexpression in DF-1 cells not only downregulated the expression levels of chp53 and of the antiviral innate immunity genes in chickens but also promoted IBDV replication. Our results suggest that gga-miR-2127 downregulates chp53 mRNA translation by targeting its 3'UTR and attenuates chp53-mediated antiviral innate immune response against IBDV. (C) 2016 Elsevier B.V. All rights reserved.