NAC1 Potentiates Cellular Antiviral Signaling by Bridging MAVS and TBK1
NAC1 Potentiates Cellular Antiviral Signaling by Bridging MAVS and TBK1
复制标题
NAC1 通过桥接 MAVS 和 TBK1 增强细胞抗病毒信号传导
DOI：
10.4049/jimmunol.1801110
复制
发表时间：
2019-08-15
影响因子：
4.4
通讯作者：
Zhu, Ying
中科院分区：
文献类型：
--
作者：
Xia, Zhangchuan;Xu, Gang;Zhu, Ying
NAC 1增强病毒诱导的IFN信号传导和TBK 1和IRF 3的激活。NAC 1抑制RNA病毒的复制。NAC 1促进TBK 1在病毒感染后募集至MAVS。细胞内病毒RNA由RIG-I样受体（RLR）识别，RIG-I样受体（RLR）通过线粒体抗病毒信号传导蛋白MAVS发出信号。MAVS募集并激活TBK 1激酶，TBK 1激酶进一步磷酸化并激活转录因子IRF 3，导致I型IFN和下游抗病毒基因的诱导。我们确定了人核转录因子相关蛋白1（NAC 1），BTB/POZ家族的一员，作为MAVS和TBK 1的桥梁，积极调节TLR介导的I型IFN的诱导。NAC 1的过表达或敲低可分别增强或削弱仙台病毒触发的TBK 1和IRF 3的活化以及IFN-β的诱导。NAC 1还显著增强了宿主对多种RNA病毒的抗病毒应答。NAC 1能够在病毒感染后与MAVS和TBK 1相互作用。NAC 1的BTB/POZ结构域（aa 1-133）与MAVS相互作用，NAC 1的其余部分与TBK 1结合。此外，NAC 1可以促进TBK 1向MAVS的募集。相反，NAC 1的敲低减弱了TBK 1和MAVS之间的相互作用。总的来说，我们的研究将NAC 1描述为TLR介导的先天免疫反应的重要组成部分，并揭示了BTB/POZ家族蛋白以前未被认识的功能。
Key Points NAC1 enhances the virus-induced IFN signaling and activation of TBK1 and IRF3. NAC1 inhibits the replication of RNA viruses. NAC1 promotes the recruitment of TBK1 to MAVS upon viral infection. Intracellular viral RNAs are recognized by the RIG-I–like receptors (RLRs), which signal through the mitochondrial antiviral signaling protein MAVS. MAVS recruits and activates TBK1 kinase, which further phosphorylates and activates the transcription factor IRF3, leading to the induction of type I IFN and downstream antiviral genes. We identified human nucleus accumbens–associated 1 (NAC1), a member of the BTB/POZ family, as a bridge for MAVS and TBK1 that positively regulates the RLR-mediated induction of type I IFN. Overexpression or knockdown of NAC1 could, respectively, enhance or impair Sendai virus–triggered activation of TBK1 and IRF3, as well as induction of IFN-β. NAC1 also significantly boosted host antiviral responses against multiple RNA viruses. NAC1 was able to interact with MAVS and TBK1 upon viral infection. The BTB/POZ domain (aa 1–133) of NAC1 interacted with MAVS, and the remainder of NAC1 bound to TBK1. Furthermore, NAC1 could promote the recruitment of TBK1 to MAVS. In contrast, knockdown of NAC1 attenuated the interaction between TBK1 and MAVS. Collectively, our study characterizes NAC1 as an important component of RLR-mediated innate immune responses and uncovers a previously unrecognized function of the BTB/POZ family proteins.