Department of Immunology, School of Medicine, University of Washington, Seattle, Washington, USA.
Immunol Rev. 2021 Nov;304(1):77-96. doi: 10.1111/imr.13019. Epub 2021 Aug 17.
From the initial sensing of viral nucleotides by pattern recognition receptors, through the induction of type I and III interferons (IFN), upregulation of antiviral effector proteins, and resolution of the inflammatory response, each step of innate immune signaling is under tight control. Though innate immunity is often associated with broad regulation at the level of gene transcription, RNA-centric post-transcriptional processes have emerged as critical mechanisms for ensuring a proper antiviral response. Here, we explore the diverse RNA regulatory mechanisms that modulate the innate antiviral immune response, with a focus on RNA sensing by RIG-I-like receptors (RLR), interferon (IFN) and IFN signaling pathways, viral pathogenesis, and host genetic variation that contributes to these processes. We address the post-transcriptional interactions with RNA-binding proteins, non-coding RNAs, transcript elements, and modifications that control mRNA stability, as well as alternative splicing events that modulate the innate immune antiviral response.
从模式识别受体对病毒核苷酸的初始感应,到 I 型和 III 型干扰素 (IFN) 的诱导、抗病毒效应蛋白的上调,以及炎症反应的解决,先天免疫信号的每一个步骤都受到严格的控制。尽管先天免疫通常与基因转录水平的广泛调控有关,但以 RNA 为中心的转录后过程已成为确保适当抗病毒反应的关键机制。在这里,我们探讨了调节先天抗病毒免疫反应的多种 RNA 调节机制,重点关注 RIG-I 样受体 (RLR)、干扰素 (IFN) 和 IFN 信号通路、病毒发病机制以及宿主遗传变异对这些过程的影响。我们讨论了与 RNA 结合蛋白、非编码 RNA、转录元件和修饰的转录后相互作用,这些相互作用控制着 mRNA 的稳定性,以及调节先天免疫抗病毒反应的可变剪接事件。