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DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression

by Hongyan Guo 1,2,3,†, Anchun Cheng 1,2,3,*, Xingcui Zhang 1,2,3,†, YuHong Pan 1,2,3,†, Mingshu Wang 1,2,3, Juan Huang 1,2,3, Dekang Zhu 1,2,3, Shun Chen 1,2,3, Mafeng Liu 1,2,3, Xinxin Zhao 1,2,3, Ying Wu 1,2,3, Qiao Yang 1,2,3, Shaqiu Zhang 1,2,3, Yanling Yu 1,2,3, Leichang Pan 1,2,3, Bin Tian 1,2,3, Mujeeb Ur Rehman 1,2,3, Xiaoyue Chen 1,2,3, Yunya Liu 1,2,3, Ling Zhang 1,2,3, Zhongqiong Yin 3, Bo Jing 3 and Renyong Jia 1,2,3,*
Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China
Authors to whom correspondence should be addressed.
These authors contributed equality to this work.
Viruses 2020, 12(1), 94;
Received: 10 October 2019 / Revised: 23 December 2019 / Accepted: 11 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue Flavivirus Replication and Pathogenesis)
Duck tembusu virus (DTMUV) is a single-stranded, positive-polarity RNA flavivirus that has caused considerable economic losses in China in recent years. Innate immunity represents the first line of defense against invading pathogens and serves as an important role in resisting viral infections. In this study, we found that the infection of ducks by DTMUV triggers Toll-like receptors (TLRs) and (RIG-I)-like receptors (RLRs) signaling pathways and inducing abundant of pro-inflammatory factors and type I interferons (IFNs), in which melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 3 (TLR3) play important immunity roles, they can inhibit the replication process of DTMUV via inducing type I IFNs. Moreover, we demonstrated that type I IFNs can inhibit the DTMUV replication process in a time- and dose-dependent manner. Exosomes are small membrane vesicles that have important roles in intercellular communication. MicroRNAs (miRNAs) are small non-coding RNAs that can modulate gene expression and are common substances in exosomes. In our experiment, we successfully isolated DEF cells derived exosome for the first time and explored its function. Firstly, we found the expression of miR-148a-5p is significantly decreased following DTMUV infect. Then we found miR-148a-5p can target TLR3 and down-regulate the expression of TLR3, serving as a negative factor in innate immunity. Unfortunately, we cannot find miRNAs with different expression changes that can target MDA5. Lastly, our experimental results showed that TLR3 was one of the causes of miR-148a-5p reduction, suggesting that the high level of TLR3 after DTMUV infect can both trigger innate immunity and suppress miR-148a-5p to resist DTMUV. View Full-Text
Keywords: innate immunity; TLRs; DTMUV; exosome; miRNA innate immunity; TLRs; DTMUV; exosome; miRNA
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Guo, H.; Cheng, A.; Zhang, X.; Pan, Y.; Wang, M.; Huang, J.; Zhu, D.; Chen, S.; Liu, M.; Zhao, X.; Wu, Y.; Yang, Q.; Zhang, S.; Yu, Y.; Pan, L.; Tian, B.; Rehman, M.U.; Chen, X.; Liu, Y.; Zhang, L.; Yin, Z.; Jing, B.; Jia, R. DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression. Viruses 2020, 12, 94.

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