Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.
Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.
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DOI：
10.1080/22221751.2020.1806735
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发表时间：
2020-12
影响因子：
13.2
通讯作者：
Quer J
中科院分区：
文献类型：
--
作者：
Andrés C;Garcia-Cehic D;Gregori J;Piñana M;Rodriguez-Frias F;Guerrero-Murillo M;Esperalba J;Rando A;Goterris L;Codina MG;Quer S;Martín MC;Campins M;Ferrer R;Almirante B;Esteban JI;Pumarola T;Antón A;Quer J
SARS-CoV-2刺突(S)蛋白是病毒结合和进入宿主细胞的媒介，作为疫苗开发和中和抗体治疗的靶标引起了极大的兴趣。初步数据表明，该病毒的突变率较低，但其庞大的基因组可以促进重组、插入和缺失，正如其他冠状病毒所描述的那样。在这里，我们对来自18例患者（10例轻度和8例重度COVID-19）的完整SARS-CoV-2 S基因进行了深度测序，发现病毒在上游和非常靠近S1/S2切割位点（PRRAR/S）积累缺失，产生一个具有停止密码子外观的移码。在所有轻度COVID-19患者和一半重度COVID-19患者的样本中，在一小部分病毒准种（2.2%）中发现了这些缺失。我们的结果表明，病毒可能产生释放到循环的游离S1蛋白。我们认为自然选择倾向于“不烧房子”的策略，在这种策略中，游离的S1蛋白可能会与病毒颗粒竞争ACE2受体，从而在不丧失传播能力的情况下降低感染和组织损伤的严重程度。
The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site (PRRAR/S), generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We suggest that natural selection has favoured a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.
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DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
3.7
作者：
Matsushita K;Ding N;Kou M;Hu X;Chen M;Gao Y;Honda Y;Zhao D;Dowdy D;Mok Y;Ishigami J;Appel LJ
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影响因子：
4.6
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通讯作者：
Drosten C
影响因子：
5.4
作者：
HENDRICKS, DA;MCINTOSH, K;PATTERSON, JL
通讯作者：
PATTERSON, JL
DOI：
10.1016/b978-0-12-801364-9.00025-0
发表时间：
2015-04-24
期刊：
The Protective Arm of the Renin Angiotensin System (RAS)
影响因子：
--
作者：
Turner AJ
通讯作者：
Turner AJ