Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients
Andrés, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Cehic, D. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gregori i Font, Josep (Roche Diagnostics SL (Sant Cugat del Valles))
Piñana, Maria (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez Frías, Francisco (Universitat Autònoma de Barcelona)
Guerrero Murillo, Mercedes (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Esperalba, Juliana (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rando-Segura, Ariadna (Hospital Universitari Vall d'Hebron)
Goterris, Lidia (Hospital Universitari Vall d'Hebron)
Codina, María Gema (Hospital Universitari Vall d'Hebron)
Quer, Susanna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martín, Maria Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Campins Martí, Magda (Hospital Universitari Vall d'Hebron)
Ferrer, Ricard (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Almirante Gragera, Benito (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Esteban Mur, Juan Ignacio (Universitat Autònoma de Barcelona)
Pumarola Suñé, Tomàs (Universitat Autònoma de Barcelona)
Antón, Andrés (Universitat Autònoma de Barcelona)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Data:	2020
Resum:	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.
Ajuts:	Instituto de Salud Carlos III RD16/0016/0003
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca
Matèria:	COVID-19 ; SARS-CoV-2 ; Deletions ; Quasispecies ; NGS ; Respiratory virus ; Diversity
Publicat a:	Emerging microbes & infections, Vol. 9 Núm. 1 (september 2020) , p. 1900-1911, ISSN 2222-1751

DOI: 10.1080/22221751.2020.1806735
PMID: 32752979

13 p, 3.0 MB

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