Lee Eun-Young, Lee Hyun-Cheol, Kim Hyun-Kwan, Jang Song Yee, Park Seong-Jun, Kim Yong-Hoon, Kim Jong Hwan, Hwang Jungwon, Kim Jae-Hoon, Kim Tae-Hwan, Arif Abul, Kim Seon-Young, Choi Young-Ki, Lee Cheolju, Lee Chul-Ho, Jung Jae U, Fox Paul L, Kim Sunghoon, Lee Jong-Soo, Kim Myung Hee
Infection and Immunity Research Laboratory, Microbiomics and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
Nat Immunol. 2016 Nov;17(11):1252-1262. doi: 10.1038/ni.3542. Epub 2016 Sep 5.
The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.
哺乳动物细胞质多tRNA合成酶复合体（MSC）是一种调节非翻译细胞功能的储存系统。在此，我们发现MSC组分谷氨酰-脯氨酰-tRNA合成酶（EPRS）在病毒感染后会转变其功能，并展现出强大的抗病毒活性。EPRS在Ser990位点的感染特异性磷酸化诱导其与MSC解离，之后它被导向抗病毒信号通路，在该通路中它与PCBP2相互作用，PCBP2是线粒体抗病毒信号蛋白（MAVS）的负调节因子，对抗病毒免疫至关重要。这种相互作用阻断了PCBP2介导的MAVS泛素化，最终抑制了病毒复制。EPRS单倍体（Eprs）小鼠表现出病毒血症增强、炎症加剧以及病毒清除延迟。EPRS对MAVS的这种刺激诱导激活表明，MSC作为病毒感染免疫反应调节因子具有意想不到的作用。
