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Open AccessArticle

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

by 1,2,3,†, 1,2,3,†, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 3 and 1,2,3,*
1
Research Center of Avian Disease, Sichuan Agricultural University, Chengdu 611130, China
2
Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
3
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China
*
Author to whom correspondence should be addressed.
These authors have contributed equally to this work.
Vaccines 2020, 8(1), 22; https://doi.org/10.3390/vaccines8010022
Received: 27 November 2019 / Revised: 8 January 2020 / Accepted: 10 January 2020 / Published: 13 January 2020
(This article belongs to the Special Issue Virus Immune Escape and Host Immune System)
Duck Tembusu virus (DTMUV) has recently appeared in ducks in China and the key cellular determiners for DTMUV replication in host cells remain unknown. Autophagy is an evolutionarily conserved cellular process that has been reported to facilitate flavivirus replication. In this study, we utilized primary duck embryo fibroblast (DEF) as the cell model and found that DTMUV infection triggered LC3-II increase and polyubiquitin-binding protein sequestosome 1 (p62) decrease, confirming that complete autophagy occurred in DEF cells. The induction of autophagy by pharmacological treatment increased DTMUV replication in DEF cells, whereas the inhibition of autophagy with pharmacological treatments or RNA interference decreased DTMUV replication. Inhibiting autophagy enhanced the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 7 (IRF7) pathways and increased the p62 protein level in DTMUV-infected cells. We further found that the overexpression of p62 decreased DTMUV replication and inhibited the activation of the NF-κB and IRF7 pathways, and changes in the NF-κB and IRF7 pathways were consistent with the level of phosphorylated TANK-binding kinase 1 (p-TBK1). Opposite results were found in p62 knockdown cells. In summary, we found that autophagy-mediated p62 degradation acted as a new strategy for DTMUV to evade host innate immunity. View Full-Text
Keywords: duck tembusu virus; autophagy; p62; p-TBK1; NF-κB; IRF7 duck tembusu virus; autophagy; p62; p-TBK1; NF-κB; IRF7
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MDPI and ACS Style

Hu, Z.; Pan, Y.; Cheng, A.; Zhang, X.; Wang, M.; Chen, S.; Zhu, D.; Liu, M.; Yang, Q.; Wu, Y.; Zhao, X.; Huang, J.; Zhang, S.; Mao, S.; Ou, X.; Yu, Y.; Zhang, L.; Liu, Y.; Tian, B.; Pan, L.; Rehman, M.U.; Yin, Z.; Jia, R. Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro. Vaccines 2020, 8, 22. https://doi.org/10.3390/vaccines8010022

AMA Style

Hu Z, Pan Y, Cheng A, Zhang X, Wang M, Chen S, Zhu D, Liu M, Yang Q, Wu Y, Zhao X, Huang J, Zhang S, Mao S, Ou X, Yu Y, Zhang L, Liu Y, Tian B, Pan L, Rehman MU, Yin Z, Jia R. Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro. Vaccines. 2020; 8(1):22. https://doi.org/10.3390/vaccines8010022

Chicago/Turabian Style

Hu, Zhiqiang; Pan, Yuhong; Cheng, Anchun; Zhang, Xingcui; Wang, Mingshu; Chen, Shun; Zhu, Dekang; Liu, Mafeng; Yang, Qiao; Wu, Ying; Zhao, Xinxin; Huang, Juan; Zhang, Shaqiu; Mao, Sai; Ou, Xumin; Yu, Yanling; Zhang, Ling; Liu, Yunya; Tian, Bin; Pan, Leichang; Rehman, Mujeeb U.; Yin, Zhongqiong; Jia, Renyong. 2020. "Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro" Vaccines 8, no. 1: 22. https://doi.org/10.3390/vaccines8010022

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