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Open AccessArticle

Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro

by 1,2,*,†, 2,3,†, 1,†, 2,3, 2,3, 1, 1, 1, 1, 2,3, 1,3 and 2,3,*
1
College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China
2
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Ya’an 625014, China
3
Institute of Animal Nutrition, Sichuan Agricultural University, Ya’an 625014, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(14), 3562; https://doi.org/10.3390/ijms20143562
Received: 10 June 2019 / Revised: 9 July 2019 / Accepted: 16 July 2019 / Published: 21 July 2019
(This article belongs to the Section Molecular Immunology)
(1) Background: Vitamin D (VD) plays a vital role in anti-viral innate immunity. However, the role of VD in anti-rotavirus and its mechanism is still unclear. The present study was performed to investigate whether VD alleviates rotavirus (RV) infection through a microRNA-155-5p (miR-155-5p)-mediated regulation of TANK-binding kinase 1 (TBK1)/interferon regulatory factors 3 (IRF3) signaling pathway in vivo and in vitro. (2) Methods: The efficacy of VD treatment was evaluated in DLY pig and IPEC-J2. Dual-luciferase reporter activity assay was performed to verify the role of miR-155-5p in 1α,25-dihydroxy-VD3 (1,25D3) mediating the regulation of the TBK1/IRF3 signaling pathway. (3) Results: A 5000 IU·kg–1 dietary VD3 supplementation attenuated RV-induced the decrease of the villus height and crypt depth (p < 0.05), and up-regulated TBK1, IRF3, and IFN-β mRNA expressions in the jejunum (p < 0.05). Incubation with 1,25D3 significantly decreased the RV mRNA expression and the RV antigen concentration, and increased the TBK1 mRNA and protein levels, and the phosphoprotein IRF3 (p-IRF3) level (p < 0.05). The expression of miR-155-5p was up-regulated in response to an RV infection in vivo and in vitro (p < 0.05). 1,25D3 significantly repressed the up-regulation of miR-155-5p in vivo and in vitro (p < 0.05). Overexpression of miR-155-5p remarkably suppressed the mRNA and protein levels of TBK1 and p-IRF3 (p < 0.01), while the inhibition of miR-155-5p had an opposite effect. Luciferase activity assays confirmed that miR-155-5p regulated RV replication by directly targeting TBK1, and miR-155-5p suppressed the TBK1 protein level (p < 0.01). (4) Conclusions: These results indicate that miR-155-5p is involved in 1,25D3 mediating the regulation of the TBK1/IRF3 signaling pathway by directly targeting TBK1. View Full-Text
Keywords: VD; rotavirus; TBK1/IRF3; microRNA-155-5p; pigs; IPEC-J2 VD; rotavirus; TBK1/IRF3; microRNA-155-5p; pigs; IPEC-J2
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MDPI and ACS Style

Zhao, Y.; Ran, Z.; Jiang, Q.; Hu, N.; Yu, B.; Zhu, L.; Shen, L.; Zhang, S.; Chen, L.; Chen, H.; Jiang, J.; Chen, D. Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro. Int. J. Mol. Sci. 2019, 20, 3562. https://doi.org/10.3390/ijms20143562

AMA Style

Zhao Y, Ran Z, Jiang Q, Hu N, Yu B, Zhu L, Shen L, Zhang S, Chen L, Chen H, Jiang J, Chen D. Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro. International Journal of Molecular Sciences. 2019; 20(14):3562. https://doi.org/10.3390/ijms20143562

Chicago/Turabian Style

Zhao, Ye; Ran, Zhiming; Jiang, Qin; Hu, Ningming; Yu, Bing; Zhu, Li; Shen, Linyuan; Zhang, Shunhua; Chen, Lei; Chen, Hong; Jiang, Jun; Chen, Daiwen. 2019. "Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro" Int. J. Mol. Sci. 20, no. 14: 3562. https://doi.org/10.3390/ijms20143562

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