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

doi:10.1038/ni.3542

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

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

40 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 language	English
Pages (from-to)	1252-1262
Number of pages	11
Journal	Nature Immunology
Volume	17
Issue number	11
DOIs	https://doi.org/10.1038/ni.3542
Publication status	Published - 2016 Oct 19

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

Access to Document

10.1038/ni.3542

Cite this

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

Lee, Eun Young ; Lee, Hyun Cheol ; Kim, Hyun Kwan ; Jang, Song Yee ; Park, Seong Jun ; Kim, Yong Hoon ; Kim, Jong Hwan ; Hwang, Jungwon ; Kim, Jae Hoon ; Kim, Tae Hwan ; Arif, Abul ; Kim, Seon Young ; Choi, Young Ki ; Lee, Cheolju ; Lee, Chul Ho ; Jung, Jae U. ; Fox, Paul L. ; Kim, Sunghoon ; Lee, Jong Soo ; Kim, Myung Hee. / Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity. In: Nature Immunology. 2016 ; Vol. 17, No. 11. pp. 1252-1262.

@article{e21fe61a1ccf495196781c1a6ae40fed,

title = "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 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.",

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

year = "2016",

month = oct,

day = "19",

doi = "10.1038/ni.3542",

language = "English",

volume = "17",

pages = "1252--1262",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "11",

}

Lee, EY, Lee, HC, Kim, HK, Jang, SY, Park, SJ, Kim, YH, Kim, JH, Hwang, J, Kim, JH, Kim, TH, Arif, A, Kim, SY, Choi, YK, Lee, C, Lee, CH, Jung, JU, Fox, PL, Kim, S, Lee, JS & Kim, MH 2016, 'Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity', Nature Immunology, vol. 17, no. 11, pp. 1252-1262. https://doi.org/10.1038/ni.3542

Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity. / Lee, Eun Young; Lee, Hyun Cheol; Kim, Hyun Kwan; Jang, Song Yee; Park, Seong Jun; Kim, Yong Hoon; Kim, Jong Hwan; Hwang, Jungwon; Kim, Jae Hoon; Kim, Tae Hwan; Arif, Abul; Kim, Seon Young; Choi, Young Ki; Lee, Cheolju; Lee, Chul Ho; Jung, Jae U.; Fox, Paul L.; Kim, Sunghoon; Lee, Jong Soo; Kim, Myung Hee.

In: Nature Immunology, Vol. 17, No. 11, 19.10.2016, p. 1252-1262.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity

AU - Lee, Eun Young

AU - Lee, Hyun Cheol

AU - Kim, Hyun Kwan

AU - Jang, Song Yee

AU - Park, Seong Jun

AU - Kim, Yong Hoon

AU - Kim, Jong Hwan

AU - Hwang, Jungwon

AU - Kim, Jae Hoon

AU - Kim, Tae Hwan

AU - Arif, Abul

AU - Kim, Seon Young

AU - Choi, Young Ki

AU - Lee, Cheolju

AU - Lee, Chul Ho

AU - Jung, Jae U.

AU - Fox, Paul L.

AU - Kim, Sunghoon

AU - Lee, Jong Soo

AU - Kim, Myung Hee

PY - 2016/10/19

Y1 - 2016/10/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84991574461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991574461&partnerID=8YFLogxK

U2 - 10.1038/ni.3542

DO - 10.1038/ni.3542

M3 - Article

C2 - 27595231

AN - SCOPUS:84991574461

VL - 17

SP - 1252

EP - 1262

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 11

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this