Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai 201306, China;
National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai 201306, China.
J Immunol. 2018 Aug 1;201(3):982-994. doi: 10.4049/jimmunol.1800377. Epub 2018 Jul 2.
Viral infection induces type I IFN production, which plays critical roles in orchestrating the antiviral defense by inducing direct antiviral activities. To establish a persistent infection, viruses have evolved numerous strategies to specifically interfere with IFN production or its downstream mediators, thereby evading the immune responses. MicroRNAs (miRNAs) are a family of small noncoding RNAs that posttranscriptionally regulate the expressions of specific target genes. Although accumulating evidence demonstrates that miRNAs play vital roles in regulating viral infection, miRNAs that target intracellular sensors and adaptors of innate immunity have not been fully uncovered. In this paper, we identify fish miR-210 as a robust regulator involved in regulating virus-host interactions. We found that rhabdovirus significantly upregulated the expression of fish miR-210. Inducible miR-210 modulates virus-triggered type I IFN and inflammatory cytokine production by targeting stimulator of IFN genes (STING), thereby promoting viral replication. Furthermore, we demonstrated that miR-210 regulates innate immune response through NF-κB, IFN regulatory factor 3, and JAK/STAT signaling pathways. The collective findings indicate that inducible miR-210 plays a regulatory role in virus-host interactions through STING-mediated singling pathway by targeting STING.
病毒感染诱导 I 型干扰素（IFN）的产生，在诱导直接抗病毒活性方面，IFN 对于协调抗病毒防御起着关键作用。为了建立持续性感染，病毒已经进化出许多策略来专门干扰 IFN 的产生或其下游介质，从而逃避免疫反应。微小 RNA（miRNA）是一类小的非编码 RNA，通过转录后调控特定靶基因的表达。尽管越来越多的证据表明 miRNA 在调控病毒感染中发挥着重要作用，但针对先天免疫的细胞内传感器和衔接蛋白的 miRNA 尚未被完全揭示。在本文中，我们鉴定出鱼类 miR-210 是一种参与调控病毒-宿主相互作用的强大调节剂。我们发现弹状病毒显著地上调了鱼类 miR-210 的表达。诱导型 miR-210 通过靶向干扰素基因刺激因子（STING）来调节病毒触发的 I 型 IFN 和炎症细胞因子的产生，从而促进病毒复制。此外，我们证明 miR-210 通过 NF-κB、IFN 调节因子 3 和 JAK/STAT 信号通路来调节先天免疫反应。这些发现表明，诱导型 miR-210 通过靶向 STING 来调节 STING 介导的信号通路，在病毒-宿主相互作用中发挥调节作用。
