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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)与开放阅读框3a(ORF3a):非同义突变、功能结构域与病毒致病机制

SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis.

作者信息

Issa Elio, Merhi Georgi, Panossian Balig, Salloum Tamara, Tokajian Sima

机构信息

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon.

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon

出版信息

mSystems. 2020 May 5;5(3):e00266-20. doi: 10.1128/mSystems.00266-20.

DOI:10.1128/mSystems.00266-20
PMID:32371472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7205519/
Abstract

The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein's structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation. At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.

摘要

非同义突变的快速积累对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)发病机制的影响尚不清楚。3a蛋白是SARS-CoV特有的,对疾病发病机制至关重要。我们的研究旨在确定SARS-CoV-2中3a蛋白的非同义突变,并与SARS-CoV中的3a蛋白相比,确定和表征该蛋白的结构和空间取向。在2782株SARS-CoV-2毒株的3a蛋白中总共检测到51种不同的非同义氨基酸替换。我们在由非同义突变定义的ORF3a基因树中观察到微克隆性,这些突变将分离株分为不同的亚群。我们在SARS-CoV-2 3a蛋白中检测并鉴定出六个功能域(I至VI)。这些功能域与毒力、感染性、离子通道形成和病毒释放有关。我们的研究显示了跨物种屏障的保守功能域的重要性,并揭示了3a蛋白在病毒生命周期中的可能作用。本研究报告的观察结果值得进行实验证实。在2019冠状病毒病(COVID-19)大流行激增期间,我们在SARS-CoV-2 3a蛋白中检测并鉴定出六个功能域(I至VI)。我们的分析表明,这些功能域与SARS-CoV-2 3a中的毒力、感染性、离子通道形成和病毒释放有关。我们的研究还揭示了跨物种屏障的保守结构域的功能重要性。本研究报告的观察结果值得进行实验证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01f8/7205519/ece91171da5a/mSystems.00266-20-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01f8/7205519/cb4118c31f45/mSystems.00266-20-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01f8/7205519/ece91171da5a/mSystems.00266-20-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01f8/7205519/cb4118c31f45/mSystems.00266-20-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01f8/7205519/ece91171da5a/mSystems.00266-20-f0002.jpg

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