Open AccessPLA1A Participates in the Antiviral Innate Immune Response by Facilitating the Recruitment of TANK-Binding Kinase 1 to Mitochondria
Author(s) -
Xiaoxiao Gao,
Dan Chen,
Xue Hu,
Yuan Zhou,
Yun Wang,
Chunchen Wu,
Jizheng Chen,
Yanyi Wang,
Rongjuan Pei,
Xinwen Chen
Publication year - 2018
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000489832
Subject(s) - tank binding kinase 1 , irf3 , microbiology and biotechnology , interferon regulatory factors , innate immune system , gene knockdown , signal transducing adaptor protein , biology , signal transduction , small interfering rna , interferon , trif , phosphorylation , kinase , protein kinase a , immune system , biochemistry , map kinase kinase kinase , immunology , apoptosis , toll like receptor , transfection , gene
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.