Deletion in the C-terminal region of the envelope glycoprotein in some of the Indian SARS-CoV-2 genome.

Deletion in the C-terminal region of the envelope glycoprotein in some of the Indian SARS-CoV-2 genome.
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DOI:
10.1016/j.virusres.2020.198222
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发表时间:
2021-01-02
期刊:
影响因子:
5
通讯作者:
Karunasagar I
Karunasagar I
中科院分区:
医学3区
文献类型:
--
作者:
Kumar BK;Rohit A;Prithvisagar KS;Rai P;Karunasagar I;Karunasagar I

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首次观察到印度SARS-CoV-2中E蛋白C-末端区域的氨基酸残基广泛缺失。.该缺失在印度使用的靶向E基因的RTqPCR的引物结合区域之外,来自不同邦的分离株除外,奥里萨邦的分离株在引物结合区域中存在缺失。E蛋白中的特征性框内缺失映射到存在于E蛋白的C-末端区域中的同源五聚体界面和PDZ结合基序(PBM)。缺失菌株分属于不同的分支。囊膜糖蛋白(E)是SARS冠状病毒最小的结构成分,在病毒复制过程中起着从囊膜形成到组装的重要作用。在这项研究中,对来自印度的2086个全基因组序列进行了计算机分析,首次观察到34个印度SARS-CoV-2基因组中包膜糖蛋白C-末端区域的氨基酸残基广泛缺失。根据Charité方案,这些氨基酸缺失映射到E蛋白C末端区域以及其中26个基因组中紧接反向引物结合区域后存在的同源五聚体界面和PDZ结合基序(PBM),因此,通过RT-qPCR进行检测可能不会受到阻碍,因此基于E基因的RT-qPCR仍将检测到这些分离株。来自奥里萨邦的8个基因组甚至在引物结合位点也有缺失。这些基因组的E蛋白C-末端区域的缺失可能是适应新的地理区域和宿主的结果。在34例病例中,只有9例病例的临床状况信息可用,这些病例无症状。然而,进一步的研究是必不可少的,以了解在SARS-CoV-2包膜蛋白的C端区域的氨基酸缺失的功能后果在病毒的发病机制和宿主适应。
First observation on the extensive deletion of amino acid residues in the C-terminal region of the E protein in some of the SARS-CoV-2 sequenced from the India. . The deletion is outside the primer binding region of RTqPCR targeting E gene used in India in isolates from various states except Odisha, which had deletion in primer binding region. Characteristic in-frame deletion in the E protein map to the homopentameric interface and PDZ binding motif (PBM) present in the C-terminal region of E protein. The isolates with deletions belonged to different clades. The envelope glycoprotein (E) is the smallest structural component of SARS-CoVs; plays an essential role in the viral replication starting from envelope formation to assembly. The in silico analysis of 2086 whole genome sequences from India performed in this study provides the first observation on the extensive deletion of amino acid residues in the C-terminal region of the envelope glycoprotein in 34 Indian SARS-CoV-2 genomes. These amino acid deletions map to the homopentameric interface and PDZ binding motif (PBM) present in the C-terminal region of E protein as well as immediately after the reverse primer binding region as per Charité protocol in 26 of these genomes, hence, their detection through RT-qPCR may not be hampered and therefore E gene-based RT-qPCR would still detect these isolates. Eight genomes from the State of Odisha had deletion even in the primer binding site. It is possible that the deletions in the C-terminal region of E protein of these genomes are a result of adapting to a newer geographical area and host. The information on the clinical status was available only for 9 out of 34 cases and these were asymptomatic. However, further studies are indispensable to understand the functional consequences of amino acid deletion in the C terminal region of SARS-CoV-2 envelope protein in the viral pathogenesis and host adaptation.
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