Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19.
Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19.
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DOI：
10.3389/fmicb.2022.854567
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发表时间：
2022
影响因子：
5.2
通讯作者：
Zhao RY
中科院分区：
文献类型：
--
作者：
Zhang J;Ejikemeuwa A;Gerzanich V;Nasr M;Tang Q;Simard JM;Zhao RY
持续的SARS-CoV-2大流行因其持续性、COVID-19相关的发病率和死亡率以及病毒的高度变异性而震惊了世界。其中一个主要问题是出现新的病毒变异，可能会增加病毒传播和疾病的严重程度。除了刺突蛋白的突变之外，还必须考虑影响毒力的病毒蛋白的突变，例如ORF 3a。本文综述了近年来关于ORF 3a的研究进展，并对SARS-CoV-2 ORF 3a的分子作用及其在病毒致病和COVID-19中的作用进行了综述。ORF 3a是一种多态性多功能病毒蛋白，对SARS-CoV/SARS-CoV-2具有特异性。它是从β-CoV谱系获得的，并且可能通过病毒进化起源于蝙蝠。SARS-CoV-2 ORF 3a是一种病毒孔蛋白，可干扰宿主血浆和内膜中的离子通道活性。它可能是一种病毒体相关蛋白，在病毒通过内吞作用进入、内膜相关病毒转录和复制以及通过胞吐作用释放病毒期间对病毒生命周期发挥其作用。ORF 3a通过激活NLRP 3炎性体、HMGB 1和HIF-1α来促进促炎细胞因子和趋化因子的产生，诱导细胞先天性和促炎性免疫应答，其可以触发细胞因子风暴，特别是在缺氧条件下。ORF 3a通过细胞凋亡、坏死和焦亡诱导细胞死亡，从而导致影响COVID-19严重程度的组织损伤。ORF 3a与刺突蛋白和其他病毒蛋白一起继续沿着进化以适应人类细胞环境。新出现的ORF 3a突变如何改变SARS-CoV-2 ORF 3a的功能及其在病毒发病机制和COVID-19中的作用在很大程度上尚不清楚。本文对ORF 3a蛋白的结构、起源、进化和突变变体，以及这些特征如何影响其在病毒发病机制和COVID-19中的功能作用进行了深入分析。
The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein’s structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.
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DOI：
10.1083/jcb.200311084
发表时间：
2004-03-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.1
作者：
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DOI：
10.1038/s41579-018-0003-6
发表时间：
2018-06
期刊：
Nature reviews. Microbiology
影响因子：
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Jung JU
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影响因子：
11.8
作者：
Chen D;Zheng Q;Sun L;Ji M;Li Y;Deng H;Zhang H
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Zhang H
影响因子：
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作者：
Akerström S;Mirazimi A;Tan YJ
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