Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China; State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.
College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China.
Cell Rep. 2021 Sep 28;36(13):109761. doi: 10.1016/j.celrep.2021.109761.
Drosophila Vago is a small antiviral peptide. Its ortholog in Culex mosquito was found to be an interferon-like cytokine that limits virus replication through activating Jak/Stat signaling. However, this activation is independent of Domeless, the sole homolog of vertebrate type I cytokine receptor. How Vago activates the Jak/Stat pathway remains unknown. Herein, we report this process is dependent on integrin in kuruma shrimp (Marsupenaeus japonicus). Shrimp Vago-like (MjVago-L) plays an antiviral role by activating the Jak/Stat pathway and inducing Stat-regulated Ficolin. Blocking integrin abrogates the role of MjVago-L. The interaction between MjVago-L and integrin β3 is confirmed. An Asp residue in MjVago-L is found critical for the interaction and MjVago-L's antiviral role. Moreover, Fak, a key adaptor of integrin signaling, mediates MjVago-L-induced Jak/Stat activation. Therefore, this study reveals that integrin, as the receptor of MjVago-L, mediates Jak/Stat activation. The establishment of the MjVago-L/integrin/Fak/Jak/Stat/Ficolin axis provides insights into antiviral cytokine signaling in invertebrates.
果蝇 Vago 是一种小的抗病毒肽。在库蚊中发现其同源物是一种干扰素样细胞因子，通过激活 Jak/Stat 信号通路来限制病毒复制。然而，这种激活不依赖于脊椎动物 I 型细胞因子受体的唯一同源物 Domeless。Vago 如何激活 Jak/Stat 途径尚不清楚。在此，我们报告该过程依赖于对虾（日本对虾）中的整合素。虾类 Vago 样（MjVago-L）通过激活 Jak/Stat 途径和诱导 Stat 调节型 Ficolin 发挥抗病毒作用。阻断整合素会破坏 MjVago-L 的作用。证实了 MjVago-L 与整合素 β3 之间的相互作用。在 MjVago-L 中发现一个 Asp 残基对于相互作用和 MjVago-L 的抗病毒作用至关重要。此外，整合素信号的关键接头 Fak 介导了 MjVago-L 诱导的 Jak/Stat 激活。因此，本研究揭示了整合素作为 MjVago-L 的受体，介导了 Jak/Stat 的激活。MjVago-L/整合素/Fak/Jak/Stat/Ficolin 轴的建立为无脊椎动物抗病毒细胞因子信号提供了新的见解。
