DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression
DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression
复制标题
DEF 细胞来源的外泌体 miR-148a-5p 通过负调节 TLR3 表达促进 DTMUV 复制
DOI：
10.3390/v12010094
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发表时间：
2020-01-01
期刊：
影响因子：
4.7
通讯作者：
Jia, Renyong
中科院分区：
文献类型：
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作者：
Guo, Hongyan;Cheng, Anchun;Jia, Renyong
鸭坦布苏病毒（DTMUV）是一种单链、正极性RNA黄病毒，近年来在我国造成了相当大的经济损失。天然免疫是机体抵抗病原体入侵的第一道防线，在抵抗病毒感染中发挥重要作用。本研究发现，DTMUV感染鸭后可激活Toll样受体（TLRs）和（RIG-I）样受体（RLRs）信号通路，诱导大量促炎因子和I型干扰素（IFN）产生，其中黑色素瘤分化相关基因5（MDA 5）和Toll样受体3（TLR 3）发挥重要的免疫作用，它们可以通过诱导I型IFN抑制DTMUV的复制过程。此外，我们证明了I型IFN可以以时间和剂量依赖性的方式抑制DTMUV复制过程。外泌体是一种在细胞间通讯中起重要作用的小膜囊泡。MicroRNA（miRNAs）是一类能够调节基因表达的非编码小RNA，是外泌体中常见的物质。本实验首次成功分离了DEF细胞来源的外泌体，并对其功能进行了初步探讨。首先，我们发现DTMUV感染后miR-148 a-5 p的表达显著降低。随后我们发现miR-148 a-5 p可以靶向TLR 3，下调TLR 3的表达，在天然免疫中起负性作用。不幸的是，我们无法找到可以靶向MDA 5的具有不同表达变化的miRNA。最后，我们的实验结果表明TLR 3是导致miR-148 a-5 p减少的原因之一，这表明DTMUV感染后高水平的TLR 3既可以触发天然免疫，又可以抑制miR-148 a-5 p抵抗DTMUV。
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.