| First Author | Lee EY | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 11 | Pages | 1252-1262 |
| PubMed ID | 27595231 | Mgi Jnum | J:259146 |
| Mgi Id | MGI:6142456 | Doi | 10.1038/ni.3542 |
| Citation | Lee EY, et al. (2016) Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity. Nat Immunol 17(11):1252-1262 |
| abstractText | 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. |
