Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an City, China.
Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, College of Basic Medical Sciences, Shandong First Medical University, Tai'an City, China.
Front Immunol. 2022 Jun 15;13:916350. doi: 10.3389/fimmu.2022.916350. eCollection 2022.
In mammals, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) has been demonstrated to play a critical role in activating downstream signaling in response to viral RNA. However, its role in ducks' antiviral innate immunity is less well understood, and how gene-mediated signaling is regulated is unknown. The regulatory role of the duck laboratory of genetics and physiology 2 (duLGP2) in the duck RIG-I (duRIG-I)-mediated antiviral innate immune signaling system was investigated in this study. In duck embryo fibroblast (DEF) cells, overexpression of duLGP2 dramatically reduced duRIG-I-mediated IFN-promotor activity and cytokine expression. In contrast, the knockdown of duLGP2 led to an opposite effect on the duRIG-I-mediated signaling pathway. We demonstrated that duLGP2 suppressed the duRIG-I activation induced by duck Tembusu virus (DTMUV) infection. Intriguingly, when duRIG-I signaling was triggered, duLGP2 enhanced the production of inflammatory cytokines. We further showed that duLGP2 interacts with duRIG-I, and this interaction was intensified during DTMUV infection. In summary, our data suggest that duLGP2 downregulated duRIG-I mediated innate immunity against the Tembusu virus. The findings of this study will help researchers better understand the antiviral innate immune system's regulatory networks in ducks.
在哺乳动物中，已证实视黄酸诱导基因 I (RIG-I)-样受体 (RLR) 在激活病毒 RNA 反应的下游信号通路中发挥关键作用。然而，其在禽类抗病毒先天免疫中的作用尚不清楚，基因介导的信号通路如何被调控也尚不清楚。本研究旨在探讨鸭实验室遗传学和生理学 2 (duLGP2) 在鸭 RIG-I (duRIG-I) 介导的抗病毒先天免疫信号系统中的调控作用。在鸭胚成纤维细胞 (DEF) 中，过表达 duLGP2 可显著降低 duRIG-I 介导的 IFN 启动子活性和细胞因子表达。相反，duLGP2 的敲低对 duRIG-I 介导的信号通路产生相反的影响。我们证明 duLGP2 抑制鸭坦布苏病毒 (DTMUV) 感染诱导的 duRIG-I 激活。有趣的是，当 duRIG-I 信号被触发时，duLGP2 增强了炎症细胞因子的产生。我们进一步表明 duLGP2 与 duRIG-I 相互作用，并且这种相互作用在 DTMUV 感染期间增强。综上所述，我们的数据表明 duLGP2 下调了 duRIG-I 介导的针对坦布苏病毒的先天免疫。本研究的发现将有助于研究人员更好地理解禽类抗病毒先天免疫系统的调控网络。
