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

Abstract

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.

• Authors: Zhiqiang Hu, Yuhong Pan, Anchun Cheng, Xingcui Zhang, Mingshu Wang, Shun Chen, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Xinxin Zhao, Juan Huang, Shaqiu Zhang, Sai Mao, Xumin Ou, Yanling Yu, Ling Zhang, Yunya Liu, Bin Tian, Leichang Pan, Mujeeb Ur Rehman, Zhongqiong Yin, Renyong Jia
• Journal: Vaccines (Vaccines (Basel)) Vol. 8 Issue 1 (Jan 13 2020) ISSN: 2076-393X [Print] Switzerland
• PMID: 31941042 (Publication Type: Journal Article)