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

Eun Young Lee, Hyun Cheol Lee, Hyun Kwan Kim, Song Yee Jang, Seong Jun Park, Yong Hoon Kim, Jong Hwan Kim, Jungwon Hwang, Jae Hoon Kim, Tae Hwan Kim, Abul Arif, Seon Young Kim, Young Ki Choi, Cheolju Lee, Chul Ho Lee, Jae U. Jung, Paul L. Fox, Sunghoon Kim, Jong Soo Lee, Myung Hee Kim

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27 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1252-1262
Number of pages11
JournalNature Immunology
Volume17
Issue number11
DOIs
Publication statusPublished - 2016 Oct 19

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Lee, E. Y., Lee, H. C., Kim, H. K., Jang, S. Y., Park, S. J., Kim, Y. H., Kim, J. H., Hwang, J., Kim, J. H., Kim, T. H., Arif, A., Kim, S. Y., Choi, Y. K., Lee, C., Lee, C. H., Jung, J. U., Fox, P. L., Kim, S., Lee, J. S., & Kim, M. H. (2016). Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity. Nature Immunology, 17(11), 1252-1262. https://doi.org/10.1038/ni.3542