Transcriptional and Non-Transcriptional Activation, Posttranslational Modifications, and Antiviral Functions of Interferon Regulatory Factor 3 and Viral Antagonism by the SARS-Coronavirus.
Transcriptional and Non-Transcriptional Activation, Posttranslational Modifications, and Antiviral Functions of Interferon Regulatory Factor 3 and Viral Antagonism by the SARS-Coronavirus.
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DOI：
10.3390/v13040575
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发表时间：
2021-03-29
期刊：
影响因子：
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通讯作者：
Chattopadhyay S
中科院分区：
文献类型：
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作者：
Glanz A;Chakravarty S;Varghese M;Kottapalli A;Fan S;Chakravarti R;Chattopadhyay S
免疫系统通过快速激活先天免疫信号通路来防御入侵的病原体。干扰素调节因子3（Interferon Regulatory Factor 3，IRF 3）是一种在病毒感染后被激活的关键转录因子，主要负责在感染宿主体内建立抗病毒状态。在Irf 3 −/−小鼠中的研究表明，缺乏IRF 3会对多种病毒感染产生高度易感性。病毒感染引起IRF 3的活化以转录I型干扰素（例如，IFNβ），其负责诱导干扰素刺激基因（ISG），ISG在特定阶段起作用以限制病毒复制。除了其转录功能外，IRF 3还被激活以触发病毒感染细胞的凋亡，作为限制病毒在宿主内传播的机制，其途径称为RIG-I样受体诱导的IRF 3介导的凋亡途径（RIPA）。IRF 3的这些双重功能协同工作以介导针对病毒感染的保护性免疫。这两种途径通过IRF 3的翻译后修饰（PTMs）被差异激活。此外，PTM不仅调节IRF 3的激活和功能，还调节蛋白质的稳定性。因此，许多病毒利用病毒蛋白或劫持细胞酶来抑制IRF 3功能。本文将介绍调节IRF 3的RIPA和转录活性的PTM，并以冠状病毒为模型病毒，对IRF 3介导的天然免疫应答进行拮抗。深入了解IRF 3的细胞控制以及病毒用来破坏该系统的机制对于开发病毒诱导的病理学的新疗法至关重要。
The immune system defends against invading pathogens through the rapid activation of innate immune signaling pathways. Interferon regulatory factor 3 (IRF3) is a key transcription factor activated in response to virus infection and is largely responsible for establishing an antiviral state in the infected host. Studies in Irf3−/− mice have demonstrated the absence of IRF3 imparts a high degree of susceptibility to a wide range of viral infections. Virus infection causes the activation of IRF3 to transcribe type-I interferon (e.g., IFNβ), which is responsible for inducing the interferon-stimulated genes (ISGs), which act at specific stages to limit virus replication. In addition to its transcriptional function, IRF3 is also activated to trigger apoptosis of virus-infected cells, as a mechanism to restrict virus spread within the host, in a pathway called RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA). These dual functions of IRF3 work in concert to mediate protective immunity against virus infection. These two pathways are activated differentially by the posttranslational modifications (PTMs) of IRF3. Moreover, PTMs regulate not only IRF3 activation and function, but also protein stability. Consequently, many viruses utilize viral proteins or hijack cellular enzymes to inhibit IRF3 functions. This review will describe the PTMs that regulate IRF3′s RIPA and transcriptional activities and use coronavirus as a model virus capable of antagonizing IRF3-mediated innate immune responses. A thorough understanding of the cellular control of IRF3 and the mechanisms that viruses use to subvert this system is critical for developing novel therapies for virus-induced pathologies.
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影响因子：
21.1
作者：
Chen, Xiaojuan;Yang, Xingxing;Zheng, Yang;Yang, Yudong;Xing, Yaling;Chen, Zhongbin
通讯作者：
Chen, Zhongbin
影响因子：
6.4
作者：
Chattopadhyay S;Fensterl V;Zhang Y;Veleeparambil M;Wetzel JL;Sen GC
通讯作者：
Sen GC
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
冠状病毒类木瓜蛋白酶的去泛素化和干扰素拮抗活性
影响因子：
5.4
作者：
Clementz, Mark A.;Chen, Zhongbin;Baker, Susan C.
通讯作者：
Baker, Susan C.
影响因子：
30.5
作者：
通讯作者：
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