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.
Bibliographical noteFunding Information:
This work was supported by the Ministry for Food, Agriculture, Forestry, and Fisheries (grant no. 315044031, 316043-3, and 318039-3) and the National Research Foundation (grant no. 2015020957, 2018M3A9H 4079660, and 2018M3A9H 4078703), Republic of Korea.
This work was supported by the Ministry for Food, Agriculture, Forestry, and Fisheries (grant no. 315044031, 316043-3, and 318039-3) and the National Research Foundation (grant no. 2015020957, 2018M3A9H 4079660, and 2018M3A9H 4078703), Republic of Korea. H.-C.L., E.-S.L., and M.B.U. performed most of the experiments, with help from T.-H.K., J.-H.K., K.C., and W.A.G.C. M.J., S.K., and C.-J.K. contributed to the discussion and provided critical reagents. H.-C.L. and J.-S.L. designed the study and wrote the manuscript. J.-S.L. supervised the study. All authors helped with data analysis. We have no conflicts of interest to declare.
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All Science Journal Classification (ASJC) codes
- Insect Science