College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
Faculty of Veterinary & Animal Science, Sylhet Agricultural University, Sylhet, Bangladesh.
J Virol. 2019 Jan 4;93(2). doi: 10.1128/JVI.01291-18. Print 2019 Jan 15.
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 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. 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 and 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.
色氨酰-tRNA 合成酶（WRS）是具有非典型功能的氨酰-tRNA 合成酶（ARS）之一。全长 WRS 在细菌感染期间释放，并启动 Toll 样受体 4（TLR4）-髓样分化因子 2（MD2）复合物，引发先天免疫反应。然而，WRS 在病毒感染中的作用尚不清楚。在这里，我们表明全长 WRS 在病毒感染的早期阶段由免疫细胞分泌，并作为一种抗病毒细胞因子发挥作用。用重组 WRS 蛋白处理细胞可促进炎症细胞因子和 I 型干扰素（IFNs）的产生，并抑制 THP-1 和 Raw264.7 细胞中的病毒复制，但不能抑制 TLR4 或 MD2 骨髓来源的巨噬细胞（BMDMs）中的病毒复制。重组 WRS 蛋白的静脉内和鼻内给药可诱导先天免疫反应并阻断病毒复制。这些发现表明，分泌的全长 WRS 在诱导对病毒感染以及细菌感染的先天免疫反应中具有非典型作用。ARS 是翻译中连接特定氨基酸与其相应 tRNA 的必需酶。在高等真核生物中，一些 ARS 在细胞代谢的调节中具有额外的非典型功能。在这里，我们报告了 WRS 在抗病毒防御中的一个新的非典型功能。WRS 对病毒感染迅速作出反应，并通过诱导促炎细胞因子和 I 型 IFNs 的分泌来启动先天免疫反应，从而抑制病毒复制。因此，我们认为 WRS 是抗病毒先天免疫反应的成员。本研究的结果增强了我们对宿主防御系统的理解，并提供了关于 ARS 非典型功能的更多信息。
