The negative regulation of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway in fish
The negative regulation of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway in fish
复制标题
鱼类视黄酸诱导基因 I (RIG-I) 样受体 (RLR) 信号通路的负调控
DOI：
10.1016/j.dci.2021.104038
复制
发表时间：
2021-03-05
影响因子：
2.9
通讯作者：
Chang, Ming Xian
中科院分区：
文献类型：
--
作者：
Chang, Ming Xian
在先天免疫反应的每个阶段，都有刺激和抑制信号来调节反应的强度和特征。 RIG-I 样受体 (RLR) 信号通路在抗病毒先天免疫反应中发挥着关键作用。最近的研究揭示了病毒感染导致 RLR 介导的下游信号级联激活和 I 型干扰素 (IFN) 产生的分子机制。然而，必须严格调节抗病毒免疫反应，以防止有害的 I 型干扰素产生。以往的综述强调了RLR信号通路的负调控，其主要目标是直接调节哺乳动物中的RIG-I、MDA5、MAVS和TBK1功能。在这篇综述中，我们总结了对硬骨鱼RLR信号通路负调节因子的理解的最新进展，特别关注在稳态或病毒感染时直接或间接抑制RIG-I、MDA5、LGP2、MAVS、TRAF3、TBK1、IRF3和IRF7功能的鱼类和病毒调节机制。我们还进一步讨论了未来研究的重要方向，特别是非编码 RNA 和通过鱼类特异性 TRIM 蛋白进行的翻译后修饰。对硬骨鱼 RLR 信号通路负调节因子的了解将为潜在治疗目的的关键信息提供新的线索。
At each stage of innate immune response, there are stimulatory and inhibitory signals that modulate the strength and character of the response. RIG-I-like receptor (RLR) signaling pathway plays pivotal roles in antiviral innate immune response. Recent studies have revealed the molecular mechanisms that viral infection leads to the activation of RLRs-mediated downstream signaling cascades and the production of type I interferons (IFNs). However, antiviral immune responses must be tightly regulated in order to prevent detrimental type I IFNs production. Previous reviews have highlighted negative regulation of RLR signaling pathway, which mainly target to directly regulate RIG-I, MDA5, MAVS and TBK1 function in mammals. In this review, we summarize recent advances in our understanding of negative regulators of RLR signaling pathway in teleost, with specific focus on piscine and viral regulatory mechanisms that directly or indirectly inhibit the function of RIG-I, MDA5, LGP2, MAVS, TRAF3, TBK1, IRF3 and IRF7 both in the steady state or upon viral infection. We also further discuss important directions for future studies, especially for non-coding RNAs and post-translational modifi-cations via fish specific TRIM proteins. The knowledge of negative regulators of RLR signaling pathway in teleost will shed new light on the critical information for potential therapeutic purposes.