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Article

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

by
Ye Zhao
1,2,*,†,
Zhiming Ran
2,3,†,
Qin Jiang
1,†,
Ningming Hu
2,3,
Bing Yu
2,3,
Li Zhu
1,
Linyuan Shen
1,
Shunhua Zhang
1,
Lei Chen
1,
Hong Chen
2,3,
Jun Jiang
1,3 and
Daiwen Chen
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
Submission received: 10 June 2019 / Revised: 9 July 2019 / Accepted: 16 July 2019 / Published: 21 July 2019
(This article belongs to the Section Molecular Immunology)
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Abstract

(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.
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.; et al. 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, et al. 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, Zhiming Ran, Qin Jiang, Ningming Hu, Bing Yu, Li Zhu, Linyuan Shen, Shunhua Zhang, Lei Chen, Hong Chen, and et al. 2019. "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 20, no. 14: 3562. https://doi.org/10.3390/ijms20143562

APA 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. (2019). 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, 20(14), 3562. https://doi.org/10.3390/ijms20143562

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