Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity.

ABSTRACT: 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 vi

SUBMITTER: Lee EY 

PROVIDER: S-EPMC5173487 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature