PLA1A Participates in the Antiviral Innate Immune Response by Facilitating the Recruitment of TANK-Binding Kinase 1 to Mitochondria

• Published in: Journal of innate immunity Vol. 10; no. 4; pp. 315 - 327
• Main Authors: Gao, Xiaoxiao, Chen, Dan, Hu, Xue, Zhou, Yuan, Wang, Yun, Wu, Chunchen, Chen, Jizheng, Wang, Yanyi, Pei, Rongjuan, Chen, Xinwen
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Antigens, Human Platelet - genetics; Antigens, Human Platelet - metabolism; HEK293 Cells; Humans; Immunity, Innate; Interferon Regulatory Factor-3 - metabolism; Interferon-beta - genetics; Interferon-beta - metabolism; Mitochondria - metabolism; Mitochondria - pathology; Protein Binding; Protein Transport; Protein-Serine-Threonine Kinases - metabolism; Research Article; RNA Viruses - physiology; RNA, Small Interfering - genetics; Signal Transduction; Virus Diseases - immunology; Mitochondria; Antiviral innate immune response; TANK-binding kinase 1; PLA1A
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000489832

As a key molecule in the antiviral innate immune response, the activation of TANK-binding kinase 1 (TBK1) is under tight regulation. In this report, we identified phosphatidylserine-specific phospholipase PLA1A as a host factor that modulates the TBK1 activation. Knockdown of PLA1A expression suppressed the innate immune signaling induced by RNA viruses, while PLA1A overexpression enhanced the signaling. PLA1A functioned at the TBK1 level of the signaling pathway, as PLA1A silencing blocked TBK1, but not interferon regulatory factor 3 (IRF3) induced interferon-β (IFN-β) promoter activity. The phosphorylation and kinase activity of TBK1 was reduced in PLA1A knockdown cells. Mechanistically, PLA1A was required in TBK1-mitochondrial antiviral signaling protein (MAVS) interactions but not the interactions of TBK1 with other adaptor proteins. Furthermore, PLA1A knockdown reduced the recruitment of TBK1 and IRF3 to mitochondria, concomitant with altered mitochondria morphology.