MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression via Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.
MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression via Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.
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MicroRNA miR-214 通过靶向宿主腺苷 5α-单磷酸激活蛋白激酶促进 IFN-α 表达来抑制蛇头水泡病毒复制。
DOI：
10.3389/fimmu.2017.01775
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发表时间：
2017
影响因子：
7.3
通讯作者：
Tu J
中科院分区：
文献类型：
--
作者：
Zhang C;Feng S;Zhang W;Chen N;Hegazy AM;Chen W;Liu X;Zhao L;Li J;Lin L;Tu J
黑鱼水泡病毒（SHVV）是从患病的杂交黑鱼中分离出来的一种新的弹状病毒，近年来已成为我国的重要病原体，给黑鱼养殖带来了巨大的经济损失。然而，对其致病机制知之甚少。 MicroRNA 是一种小型非编码 RNA，可在转录后调节基因表达，并已被证明可调节几乎所有细胞过程。我们之前的研究表明，SHVV 感染后 miR-214 下调。条纹蛇头（SSN-1）细胞中miR-214的过表达抑制SHVV复制并促进IFN-α表达，而miR-214抑制剂促进SHVV复制并减少IFN-α表达。这些发现表明，miR-214 可能通过正向调节 IFN-α 表达来负向调节 SHVV 复制。进一步研究发现，5′-单磷酸腺苷激活蛋白激酶（AMPK）是miR-214的靶基因。 siRNA敲低AMPK可抑制SHVV复制并促进IFN-α表达，表明细胞AMPK正向调节SHVV复制并负向调节IFN-α表达。此外，我们发现siAMPK介导的SHVV复制抑制可以被miR-214抑制剂部分恢复，表明miR-214至少部分通过靶向AMPK抑制SHVV复制。这项研究的结果补充了我们早期的研究，并为 SHVV 致病机制提供了见解。 SHVV感染下调miR-214，反过来，下调的miR-214增加其靶基因AMPK的表达，从而通过减少IFN-α表达促进SHVV复制。因此，可以假设低水平miR-214的细胞环境有利于SHVV复制，并且SHVV通过调节细胞miR-214表达来降低IFN-α表达来逃避宿主抗病毒先天免疫。
Snakehead vesiculovirus (SHVV), a new rhabdovirus isolated from diseased hybrid snakehead, has emerged as an important pathogen during the past few years in China with great economical losses in snakehead fish cultures. However, little is known about the mechanism of its pathogenicity. MicroRNAs are small noncoding RNAs that posttranscriptionally modulate gene expression and have been indicated to regulate almost all cellular processes. Our previous study has revealed that miR-214 was downregulated upon SHVV infection. The overexpression of miR-214 in striped snakehead (SSN-1) cells inhibited SHVV replication and promoted IFN-α expression, while miR-214 inhibitor facilitated SHVV replication and reduced IFN-α expression. These findings suggested that miR-214 negatively regulated SHVV replication probably through positively regulating IFN-α expression. Further investigation revealed that adenosine 5′-monophosphate-activated protein kinase (AMPK) was a target gene of miR-214. Knockdown of AMPK by siRNA inhibited SHVV replication and promoted IFN-α expression, suggesting that cellular AMPK positively regulated SHVV replication and negatively regulated IFN-α expression. Moreover, we found that siAMPK-mediated inhibition of SHVV replication could be partially restored by miR-214 inhibitor, indicating that miR-214 inhibited SHVV replication at least partially via targeting AMPK. The findings of this study complemented our early study, and provide insights for the mechanism of SHVV pathogenicity. SHVV infection downregulated miR-214, and in turn, the downregulated miR-214 increased the expression of its target gene AMPK, which promoted SHVV replication via reducing IFN-α expression. It can therefore assume that cellular circumstance with low level of miR-214 is beneficial for SHVV replication and that SHVV evades host antiviral innate immunity through decreasing IFN-α expression via regulating cellular miR-214 expression.