Chen Luoquan, Song Yinjing, He Li, Wan Xiaopeng, Lai Lihua, Dai Feng, Liu Yang, Wang Qingqing
From the Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
From the Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China
J Biol Chem. 2016 Jul 8;291(28):14706-16. doi: 10.1074/jbc.M115.700252. Epub 2016 May 13.
Effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs. Previous reports have shown that some microRNAs are induced during virus infection and participate in the regulation of the innate antiviral response. However, whether the type I IFN response is regulated by miR-223 is still unknown. Here, we reported that vesicular stomatitis virus (VSV) infection induced significant up-regulation of miR-223 in murine macrophages. We observed that miR-223 overexpression up-regulated type I IFN expression levels in VSV-infected macrophages. We also demonstrated that miR-223 directly targets FOXO3 to regulate the type I IFN production. Furthermore, type I IFN, which is triggered by VSV infection, is responsible for the up-regulation of miR-223, thus forming a positive regulatory loop for type I IFN production. Our results uncovered a novel mechanism of miR-223-mediated regulation of type I IFN production in the antiviral innate immunity for the first time.
有效识别病毒感染并随后触发抗病毒先天免疫反应对于宿主抗病毒防御至关重要，这一过程受到包括微小RNA在内的多种调节因子的严格调控。先前的报道表明，一些微小RNA在病毒感染期间被诱导，并参与先天抗病毒反应的调节。然而，I型干扰素反应是否受miR-223调控仍不清楚。在此，我们报道水泡性口炎病毒（VSV）感染可诱导小鼠巨噬细胞中miR-223显著上调。我们观察到miR-223过表达可上调VSV感染的巨噬细胞中I型干扰素的表达水平。我们还证明miR-223直接靶向FOXO3来调节I型干扰素的产生。此外，VSV感染触发的I型干扰素负责miR-223的上调，从而形成I型干扰素产生的正调控回路。我们的结果首次揭示了miR-223在抗病毒先天免疫中介导I型干扰素产生调节的新机制。
