Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome.
Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome.
复制标题
丙酮酸羧化酶通过靶向 MAVS 信号体激活 RIG-I 样受体介导的抗病毒免疫反应
DOI：
10.1038/srep22002
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发表时间：
2016-02-24
影响因子：
4.6
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Cao Z;Zhou Y;Zhu S;Feng J;Chen X;Liu S;Peng N;Yang X;Xu G;Zhu Y
当视黄酸诱导基因1蛋白（rig - 1）样受体在细胞质中感知病毒dsRNA时，rig - 1和黑色素瘤分化相关基因5 （MDA5）被招募到线粒体，与线粒体抗病毒信号蛋白（MAVS）相互作用并启动抗病毒免疫反应。在这项研究中，我们证明了含生物素酶丙酮酸羧化酶（PC）在病毒触发的MAVS介导的核因子κB （NF-κB）信号激活中发挥了重要作用。PC有助于增强I型干扰素（ifn）和促炎细胞因子的产生，PC敲低抑制病毒引发的先天免疫反应。此外，PC对甲型流感病毒（IAV）、人肠病毒71型（EV71）和水疱性口炎病毒（VSV）等RNA病毒具有广泛的抗病毒活性。此外，PC通过靶向MAVS信号体介导抗病毒作用，并通过促进NF-κB抑制剂-α (i -κB α)和i -κB激酶（IKK）复合物的磷酸化以及NF-κB核易位诱导干扰素刺激基因（ISGs）的激活，包括双链rna依赖蛋白激酶（PKR）和黏液病毒抗性蛋白1 (Mx1)，诱导ifn和促炎细胞因子。我们的研究结果表明，PC是宿主抗病毒信号传导的重要参与者。
When retinoic acid-inducible gene 1 protein (RIG-I)-like receptors sense viral dsRNA in the cytosol, RIG-I and melanoma differentiation-associated gene 5 (MDA5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (MAVS) and initiate antiviral immune responses. In this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (PC) plays an essential role in the virus-triggered activation of nuclear factor kappa B (NF-κB) signaling mediated by MAVS. PC contributes to the enhanced production of type I interferons (IFNs) and pro-inflammatory cytokines and PC knockdown inhibits the virus-triggered innate immune response. In addition, PC shows extensive antiviral activity against RNA viruses, including influenza A virus (IAV), human enterovirus 71 (EV71) and vesicular stomatitis virus (VSV). Furthermore, PC mediates antiviral action by targeting the MAVS signalosome and induces IFNs and pro-inflammatory cytokines by promoting phosphorylation of NF-κB inhibitor-α (IκBα) and the IκB kinase (IKK) complex, as well as NF-κB nuclear translocation, which leads to activation of interferon-stimulated genes (ISGs), including double-stranded RNA-dependent protein kinase (PKR) and myxovirus resistance protein 1 (Mx1). Our findings suggest that PC is an important player in host antiviral signaling.