Chicken miR-126-5p negatively regulates antiviral innate immunity by targeting TRAF3

• Published in: Veterinary research (Paris) 2022-10, Vol.53 (1), p.82-14, Article 82
• Main Authors: Wang, Jie, Cheng, Yuqiang, Wang, Longlong, Sun, Aixi, Lin, Zhenyu, Zhu, Wenxian, Wang, Zhaofei, Ma, Jingjiao, Wang, Henan, Yan, Yaxian, Sun, Jianhe
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Animals; Antiviral agents; B cells; Bacterial infections; Binding sites; Biological response modifiers; Biology; Chicken; Chickens - genetics; Chickens - metabolism; Cloning; Cytokines; Cytokines - metabolism; Gene expression; Genes; Genomics; Immune response; Immunity, Innate - genetics; Infections; Influenza; innate immunity; Interferons - metabolism; Kinases; Laboratories; Luciferases - genetics; Luciferases - metabolism; Lymphocytes; Mammals; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-126-5p; Plasmids; Poultry; Proteins; Reagents; RNA viruses; TNF Receptor-Associated Factor 3 - genetics; TNF Receptor-Associated Factor 3 - metabolism; TRAF3; Tumor necrosis factor-TNF; Viral infections; Viruses
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/s13567-022-01098-x

Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessive activation is detrimental to immune homeostasis and even leads to a "cytokine storm" of the infected host. The host develops a series of negative regulatory mechanisms to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA. In the GEO database, we found that miR-126-5p was markedly up-regulated in chickens infected by RNA viruses. Upregulation of miR-126-5p by RNA virus was then further shown via both a cell model and in vivo tests. Overexpression of miR-126-5p significantly inhibited the expression of interferon and inflammatory cytokine-related genes induced by RNA viruses. The opposite result was achieved after the knockdown of miR-126-5p expression. Bioinformatics analysis identified TRAF3 as candidate target gene of miR-126-5p. Experimentally, miR-126-5p can target TRAF3, as shown by the effects of miR-126-5p on the endogenous expression of TRAF3, and by the TRAF3 3'UTR driven luciferase reporter assay. Furthermore, we demonstrated that miR-126-5p negatively regulated innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with a co-expression assay. Overall, our results suggest that miR-126-5p is involved in the negative regulation of chicken innate immunity, which might contribute to maintaining immune balance.