期刊
EMERGING MICROBES & INFECTIONS
卷 9, 期 1, 页码 1900-1911出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2020.1806735
关键词
SARS-CoV-2; deletions; quasispecies; NGS; respiratory virus; diversity
资金
- Direccio General de Recerca i Innovacio en Salut (DGRIS) Catalan Health Ministry Generalitat de Catalunya through Vall d'Hebron Institut de Recerca (VHIR)
- European Development Regional Fund (ERDF)A way to achieve Europe by Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0003]
- Centro para el Desarrollo Tecnologico Industrial (CDTI) from the Spanish Ministry of Economy and Business [IDI-20200297]
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 corona viruses. Here, we deep-sequenced the complete SARS-CoV-2Sgene 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 quasi species (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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