An Integrated View of Deubiquitinating Enzymes Involved in Type I Interferon Signaling, Host Defense and Antiviral Activities.
An Integrated View of Deubiquitinating Enzymes Involved in Type I Interferon Signaling, Host Defense and Antiviral Activities.
复制标题
参与 I 型干扰素信号传导、宿主防御和抗病毒活性的去泛素化酶的综合观点
DOI：
10.3389/fimmu.2021.742542
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Lv H
中科院分区：
文献类型：
--
作者：
Qian G;Zhu L;Li G;Liu Y;Zhang Z;Pan J;Lv H
病毒感染性疾病给全球人类健康带来巨大挑战。 I 型干扰素 (IFN-Is) 作为宿主防御的第一道防线，因此通过介导数百个基因的转录诱导在病毒感染过程中发挥关键作用。然而，过度活跃的细胞因子免疫反应也会引起自身免疫性疾病，因此，需要严格调节先天免疫反应，以在不引起过度免疫反应的情况下实现病毒清除。最近的新兴研究发现，泛素系统，特别是去泛素化酶（DUB），在调节先天免疫反应中发挥着关键作用。在这篇综述中，我们重点介绍了人类 DUB 与 IFN-I 信号传导相关的多种机制的最新进展。这些 DUB 通过靶向 IFN-I 信号转导途径中的中枢蛋白，动态发挥作用，校准宿主对各种病毒感染的防御。我们还对 DUB-底物相互作用网络在先天抗病毒活性中的作用提出了未来的观点，讨论了基于 DUB 的药物开发的前景和挑战，并确定了仍有待澄清的开放性问题。我们的综述提供了 DUB 的全面描述，特别是它们在宿主中进化来调节 IFN-I 信号介导的抗病毒反应的差异机制。
Viral infectious diseases pose a great challenge to human health around the world. Type I interferons (IFN-Is) function as the first line of host defense and thus play critical roles during virus infection by mediating the transcriptional induction of hundreds of genes. Nevertheless, overactive cytokine immune responses also cause autoimmune diseases, and thus, tight regulation of the innate immune response is needed to achieve viral clearance without causing excessive immune responses. Emerging studies have recently uncovered that the ubiquitin system, particularly deubiquitinating enzymes (DUBs), plays a critical role in regulating innate immune responses. In this review, we highlight recent advances on the diverse mechanisms of human DUBs implicated in IFN-I signaling. These DUBs function dynamically to calibrate host defenses against various virus infections by targeting hub proteins in the IFN-I signaling transduction pathway. We also present a future perspective on the roles of DUB-substrate interaction networks in innate antiviral activities, discuss the promises and challenges of DUB-based drug development, and identify the open questions that remain to be clarified. Our review provides a comprehensive description of DUBs, particularly their differential mechanisms that have evolved in the host to regulate IFN-I-signaling-mediated antiviral responses.