Ouyang Wei, Wang Yong-Shan, Meng Kai, Pan Qun-Xing, Wang Xiao-Li, Xia Xing-Xia, Zhu Yu-Mei, Bi Zhen-Wei, Zhang Hai-Bin, Luo Kai
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences/Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture/National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou 225009, China; First Affiliated Hospital with Nanjing Medical University/Jiangsu Province Hospital, Nanjing 210029, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences/Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture/National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou 225009, China.
Vet Microbiol. 2017 Jan;198:34-42. doi: 10.1016/j.vetmic.2016.12.007. Epub 2016 Dec 6.
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.
传染性法氏囊病（IBD）的特征是感染禽类的免疫抑制。传染性法氏囊病病毒（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。本研究建立了基于DF-1细胞（鸡胚成纤维细胞系）的体外感染模型，以研究鸡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增加。chp53的过表达抑制了IBDV的复制，并上调了多个鸡抗病毒天然免疫基因（IPS-1、IRF3、PKR、OAS和Mx）的表达，而chp53的抑制则产生相反的效果。这一结果表明，chp53激活了鸡对IBDV感染的抗病毒天然免疫反应。生物信息学分析和双荧光素酶报告基因检测表明，gga-miR-2127靶向chp53的3'UTR。qRT-PCR和蛋白质印迹显示，DF-1细胞中gga-miR-2127的过表达不仅下调了鸡chp53和抗病毒天然免疫基因的表达水平，还促进了IBDV的复制。我们的结果表明，gga-miR-2127通过靶向chp53的3'UTR下调其mRNA翻译，并减弱chp53介导的针对IBDV的抗病毒天然免疫反应。
