The Functional Deubiquitinating Enzymes in Control of Innate Antiviral Immunity.
The Functional Deubiquitinating Enzymes in Control of Innate Antiviral Immunity.
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控制先天抗病毒免疫的功能性去泛素化酶
DOI：
10.1002/advs.202002484
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Zhou F
中科院分区：
文献类型：
--
作者：
Zong Z;Zhang Z;Wu L;Zhang L;Zhou F
先天性抗病毒免疫是宿主抵御病毒病原体入侵的第一道防线。免疫激活主要依赖于模式识别受体（PRR）对病原体相关分子模式（PAMP）的识别。病毒蛋白质或核酸主要参与三类PRR：Toll样受体（TLR）、视黄酸诱导基因I（RIG-I）样受体（RLR）和DNA传感器环GMP-AMP（cGAMP）合酶（cGAS）。这些受体启动一系列信号级联反应，导致产生促炎细胞因子和I型干扰素（IFN-I），以应对病毒感染。该系统需要精确的调节以避免异常激活。新出现的证据揭示了泛素系统，特别是去泛素化酶（DUBs）在控制免疫反应中的关键作用。本文综述了DUBs在先天性抗病毒免疫途径中的作用。还提供了对病毒DUB在抵消宿主免疫反应中的作用的见解。最后，对DUBs作为感染性疾病治疗靶点的前景和挑战进行了讨论。本文系统总结了去泛素化酶（DUBs）通过Toll样受体（TLR）、RIG-I样受体（RLR）和环GMP-AMP合酶（cGAS）调节先天性抗病毒信号传导的作用和机制。病毒DUBs抵消宿主免疫反应的作用也得出结论。此外，还讨论了利用DUBs作为治疗COVID-19等传染病的治疗靶点的前景和挑战。
Innate antiviral immunity is the first line of host defense against invading viral pathogens. Immunity activation primarily relies on the recognition of pathogen‐associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Viral proteins or nucleic acids mainly engage three classes of PRRs: Toll‐like receptors (TLRs), retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs), and DNA sensor cyclic GMP‐AMP (cGAMP) synthase (cGAS). These receptors initiate a series of signaling cascades that lead to the production of proinflammatory cytokines and type I interferon (IFN‐I) in response to viral infection. This system requires precise regulation to avoid aberrant activation. Emerging evidence has unveiled the crucial roles that the ubiquitin system, especially deubiquitinating enzymes (DUBs), play in controlling immune responses. In this review, an overview of the most current findings on the function of DUBs in the innate antiviral immune pathways is provided. Insights into the role of viral DUBs in counteracting host immune responses are also provided. Furthermore, the prospects and challenges of utilizing DUBs as therapeutic targets for infectious diseases are discussed. This review systematically summarizes the role and mechanisms of deubiquitinating enzymes (DUBs) in regulating innate antiviral signaling via the Toll‐like receptors (TLRs), RIG‐I like receptors (RLRs), and cyclic GMP‐AMP synthase (cGAS). The role of viral DUBs counteracting host immune responses is also concluded. Moreover, the prospects and challenges of utilizing DUBs as therapeutic targets for treatment of infectious diseases like COVID‐19 are also discussed.
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