PMID- 30355684
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20201126
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 93
IP  - 2
DP  - 2019 Jan 15
TI  - Released Tryptophanyl-tRNA Synthetase Stimulates Innate Immune Responses against 
      Viral Infection.
LID - 10.1128/JVI.01291-18 [doi]
LID - e01291-18
AB  - Tryptophanyl-tRNA synthetase (WRS) is one of the aminoacyl-tRNA synthetases 
      (ARSs) that possesses noncanonical functions. Full-length WRS is released during 
      bacterial infection and primes the Toll-like receptor 4 (TLR4)-myeloid 
      differentiation factor 2 (MD2) complex to elicit innate immune responses. 
      However, the role of WRS in viral infection remains unknown. Here, we show that 
      full-length WRS is secreted by immune cells in the early phase of viral infection 
      and functions as an antiviral cytokine. Treatment of cells with recombinant WRS 
      protein promotes the production of inflammatory cytokines and type I interferons 
      (IFNs) and curtails virus replication in THP-1 and Raw264.7 cells but not in 
      TLR4(-/-) or MD2(-/-) bone marrow-derived macrophages (BMDMs). Intravenous and 
      intranasal administration of recombinant WRS protein induces an innate immune 
      response and blocks viral replication in vivo These findings suggest that 
      secreted full-length WRS has a noncanonical role in inducing innate immune 
      responses to viral infection as well as to bacterial infection.IMPORTANCE ARSs 
      are essential enzymes in translation that link specific amino acids to their 
      cognate tRNAs. In higher eukaryotes, some ARSs possess additional, noncanonical 
      functions in the regulation of cell metabolism. Here, we report a novel 
      noncanonical function of WRS in antiviral defense. WRS is rapidly secreted in 
      response to viral infection and primes the innate immune response by inducing the 
      secretion of proinflammatory cytokines and type I IFNs, resulting in the 
      inhibition of virus replication both in vitro and in vivo Thus, we consider WRS 
      to be a member of the antiviral innate immune response. The results of this study 
      enhance our understanding of host defense systems and provide additional 
      information on the noncanonical functions of ARSs.
CI  - Copyright (c) 2019 American Society for Microbiology.
FAU - Lee, Hyun-Cheol
AU  - Lee HC
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
FAU - Lee, Eun-Seo
AU  - Lee ES
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
FAU - Uddin, Md Bashir
AU  - Uddin MB
AUID- ORCID: 0000-0002-0045-9669
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
AD  - Faculty of Veterinary & Animal Science, Sylhet Agricultural University, Sylhet, 
      Bangladesh.
FAU - Kim, Tae-Hwan
AU  - Kim TH
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
FAU - Kim, Jae-Hoon
AU  - Kim JH
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
AD  - Laboratory Animal Resource Center, KRIBB, University of Science and Technology 
      (UST), Daejeon, Republic of Korea.
FAU - Chathuranga, Kiramage
AU  - Chathuranga K
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
FAU - Chathuranga, W A Gayan
AU  - Chathuranga WAG
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
FAU - Jin, Mirim
AU  - Jin M
AD  - Laboratory of Microbiology, College of Medicine, Gachon University, Incheon, 
      Republic of Korea.
AD  - Department of Health Science and Technology, GAIHST, Gachon University, Incheon, 
      Republic of Korea.
FAU - Kim, Sunghoon
AU  - Kim S
AD  - Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National 
      University, Gwanak-gu, Seoul, Republic of Korea.
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Gwanak-gu, 
      Seoul, Republic of Korea.
FAU - Kim, Chul-Joong
AU  - Kim CJ
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea.
FAU - Lee, Jong-Soo
AU  - Lee JS
AD  - College of Veterinary Medicine, Chungnam National University, Daejeon, Republic 
      of Korea jongsool@cnu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190104
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Cytokines)
RN  - 0 (Interferon Type I)
RN  - EC 6.1.1.2 (Tryptophan-tRNA Ligase)
RN  - EC 6.1.1.2 (WARS1 protein, human)
SB  - IM
MH  - Administration, Intranasal
MH  - Administration, Intravenous
MH  - Animals
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Immunity, Innate
MH  - Interferon Type I/metabolism
MH  - Mice
MH  - RAW 264.7 Cells
MH  - Rhabdoviridae Infections/genetics/*immunology
MH  - THP-1 Cells
MH  - Tryptophan-tRNA Ligase/administration & dosage/*genetics/*metabolism
MH  - Vesiculovirus/immunology/*pathogenicity
PMC - PMC6321899
OTO - NOTNLM
OT  - WRS
OT  - alarmin
OT  - innate immunity
OT  - virus infection
EDAT- 2018/10/26 06:00
MHDA- 2019/10/23 06:00
PMCR- 2019/07/04
CRDT- 2018/10/26 06:00
PHST- 2018/07/26 00:00 [received]
PHST- 2018/10/14 00:00 [accepted]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2019/07/04 00:00 [pmc-release]
AID - JVI.01291-18 [pii]
AID - 01291-18 [pii]
AID - 10.1128/JVI.01291-18 [doi]
PST - epublish
SO  - J Virol. 2019 Jan 4;93(2):e01291-18. doi: 10.1128/JVI.01291-18. Print 2019 Jan 
      15.