Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.
Identifieur interne : 000840 ( Main/Curation ); précédent : 000839; suivant : 000841Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.
Auteurs : Cristina Andrés [Espagne] ; Damir Garcia-Cehic [Espagne] ; Josep Gregori [Espagne] ; Maria Pi Ana [Espagne] ; Francisco Rodriguez-Frias [Espagne] ; Mercedes Guerrero-Murillo [Espagne] ; Juliana Esperalba [Espagne] ; Ariadna Rando [Espagne] ; Lidia Goterris [Espagne] ; Maria Gema Codina [Espagne] ; Susanna Quer [Espagne] ; Maria Carmen Martín [Espagne] ; Magda Campins [Espagne] ; Ricard Ferrer [Espagne] ; Benito Almirante [Espagne] ; Juan Ignacio Esteban [Espagne] ; Tomás Pumarola [Espagne] ; Andrés Ant N [Espagne] ; Josep Quer [Espagne]Source :
- Emerging microbes & infections [ 2222-1751 ] ; 2020.
Descripteurs français
- KwdFr :
- Adulte (MeSH), Adulte d'âge moyen (MeSH), Analyse de séquence d'ARN (MeSH), Betacoronavirus (génétique), Biologie informatique (MeSH), Clivage de l'ARN (MeSH), Délétion de gène (MeSH), Femelle (MeSH), Glycoprotéine de spicule des coronavirus (génétique), Génome viral (génétique), Humains (MeSH), Infections de l'appareil respiratoire (virologie), Infections à coronavirus (virologie), Mâle (MeSH), Pandémies (MeSH), Pneumopathie virale (virologie), Quasi-espèce (génétique), Sujet âgé (MeSH), Séquençage nucléotidique à haut débit (MeSH).
- MESH :
- génétique : Betacoronavirus, Glycoprotéine de spicule des coronavirus, Génome viral, Quasi-espèce.
- virologie : Infections de l'appareil respiratoire, Infections à coronavirus, Pneumopathie virale.
- Adulte, Adulte d'âge moyen, Analyse de séquence d'ARN, Biologie informatique, Clivage de l'ARN, Délétion de gène, Femelle, Humains, Mâle, Pandémies, Sujet âgé, Séquençage nucléotidique à haut débit.
English descriptors
- KwdEn :
- Adult (MeSH), Aged (MeSH), Betacoronavirus (genetics), Computational Biology (MeSH), Coronavirus Infections (virology), Female (MeSH), Gene Deletion (MeSH), Genome, Viral (genetics), High-Throughput Nucleotide Sequencing (MeSH), Humans (MeSH), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (virology), Quasispecies (genetics), RNA Cleavage (MeSH), Respiratory Tract Infections (virology), Sequence Analysis, RNA (MeSH), Spike Glycoprotein, Coronavirus (genetics).
- MESH :
- chemical , genetics : Spike Glycoprotein, Coronavirus.
- genetics : Betacoronavirus, Genome, Viral, Quasispecies.
- virology : Coronavirus Infections, Pneumonia, Viral, Respiratory Tract Infections.
- Adult, Aged, Computational Biology, Female, Gene Deletion, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Pandemics, RNA Cleavage, Sequence Analysis, RNA.
Abstract
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.
DOI: 10.1080/22221751.2020.1806735
PubMed: 32752979
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pubmed:32752979Le document en format XML
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<author><name sortKey="Garcia Cehic, Damir" sort="Garcia Cehic, Damir" uniqKey="Garcia Cehic D" first="Damir" last="Garcia-Cehic">Damir Garcia-Cehic</name>
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<author><name sortKey="Gregori, Josep" sort="Gregori, Josep" uniqKey="Gregori J" first="Josep" last="Gregori">Josep Gregori</name>
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<author><name sortKey="Pi Ana, Maria" sort="Pi Ana, Maria" uniqKey="Pi Ana M" first="Maria" last="Pi Ana">Maria Pi Ana</name>
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<author><name sortKey="Rodriguez Frias, Francisco" sort="Rodriguez Frias, Francisco" uniqKey="Rodriguez Frias F" first="Francisco" last="Rodriguez-Frias">Francisco Rodriguez-Frias</name>
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<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
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<author><name sortKey="Guerrero Murillo, Mercedes" sort="Guerrero Murillo, Mercedes" uniqKey="Guerrero Murillo M" first="Mercedes" last="Guerrero-Murillo">Mercedes Guerrero-Murillo</name>
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<author><name sortKey="Esperalba, Juliana" sort="Esperalba, Juliana" uniqKey="Esperalba J" first="Juliana" last="Esperalba">Juliana Esperalba</name>
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<author><name sortKey="Rando, Ariadna" sort="Rando, Ariadna" uniqKey="Rando A" first="Ariadna" last="Rando">Ariadna Rando</name>
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<author><name sortKey="Goterris, Lidia" sort="Goterris, Lidia" uniqKey="Goterris L" first="Lidia" last="Goterris">Lidia Goterris</name>
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<author><name sortKey="Codina, Maria Gema" sort="Codina, Maria Gema" uniqKey="Codina M" first="Maria Gema" last="Codina">Maria Gema Codina</name>
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<author><name sortKey="Quer, Susanna" sort="Quer, Susanna" uniqKey="Quer S" first="Susanna" last="Quer">Susanna Quer</name>
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<author><name sortKey="Martin, Maria Carmen" sort="Martin, Maria Carmen" uniqKey="Martin M" first="Maria Carmen" last="Martín">Maria Carmen Martín</name>
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<author><name sortKey="Campins, Magda" sort="Campins, Magda" uniqKey="Campins M" first="Magda" last="Campins">Magda Campins</name>
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<author><name sortKey="Ferrer, Ricard" sort="Ferrer, Ricard" uniqKey="Ferrer R" first="Ricard" last="Ferrer">Ricard Ferrer</name>
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</affiliation>
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<author><name sortKey="Almirante, Benito" sort="Almirante, Benito" uniqKey="Almirante B" first="Benito" last="Almirante">Benito Almirante</name>
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<author><name sortKey="Esteban, Juan Ignacio" sort="Esteban, Juan Ignacio" uniqKey="Esteban J" first="Juan Ignacio" last="Esteban">Juan Ignacio Esteban</name>
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<affiliation wicri:level="1"><nlm:affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
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</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
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<author><name sortKey="Pumarola, Tomas" sort="Pumarola, Tomas" uniqKey="Pumarola T" first="Tomás" last="Pumarola">Tomás Pumarola</name>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Universitat Autònoma de Barcelona, Bellaterra</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ant N, Andres" sort="Ant N, Andres" uniqKey="Ant N A" first="Andrés" last="Ant N">Andrés Ant N</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Universitat Autònoma de Barcelona, Bellaterra</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quer, Josep" sort="Quer, Josep" uniqKey="Quer J" first="Josep" last="Quer">Josep Quer</name>
<affiliation wicri:level="1"><nlm:affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.</title>
<author><name sortKey="Andres, Cristina" sort="Andres, Cristina" uniqKey="Andres C" first="Cristina" last="Andrés">Cristina Andrés</name>
<affiliation wicri:level="1"><nlm:affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
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<author><name sortKey="Garcia Cehic, Damir" sort="Garcia Cehic, Damir" uniqKey="Garcia Cehic D" first="Damir" last="Garcia-Cehic">Damir Garcia-Cehic</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
</affiliation>
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<author><name sortKey="Gregori, Josep" sort="Gregori, Josep" uniqKey="Gregori J" first="Josep" last="Gregori">Josep Gregori</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Roche Diagnostics SL, Sant Cugat del Valles, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
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<author><name sortKey="Pi Ana, Maria" sort="Pi Ana, Maria" uniqKey="Pi Ana M" first="Maria" last="Pi Ana">Maria Pi Ana</name>
<affiliation wicri:level="1"><nlm:affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
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</author>
<author><name sortKey="Rodriguez Frias, Francisco" sort="Rodriguez Frias, Francisco" uniqKey="Rodriguez Frias F" first="Francisco" last="Rodriguez-Frias">Francisco Rodriguez-Frias</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Biochemistry and Microbiology Departments, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Biochemistry and Microbiology Departments, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Universitat Autònoma de Barcelona, Bellaterra</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Guerrero Murillo, Mercedes" sort="Guerrero Murillo, Mercedes" uniqKey="Guerrero Murillo M" first="Mercedes" last="Guerrero-Murillo">Mercedes Guerrero-Murillo</name>
<affiliation wicri:level="1"><nlm:affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Esperalba, Juliana" sort="Esperalba, Juliana" uniqKey="Esperalba J" first="Juliana" last="Esperalba">Juliana Esperalba</name>
<affiliation wicri:level="1"><nlm:affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rando, Ariadna" sort="Rando, Ariadna" uniqKey="Rando A" first="Ariadna" last="Rando">Ariadna Rando</name>
<affiliation wicri:level="1"><nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
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<author><name sortKey="Goterris, Lidia" sort="Goterris, Lidia" uniqKey="Goterris L" first="Lidia" last="Goterris">Lidia Goterris</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
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<author><name sortKey="Codina, Maria Gema" sort="Codina, Maria Gema" uniqKey="Codina M" first="Maria Gema" last="Codina">Maria Gema Codina</name>
<affiliation wicri:level="1"><nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quer, Susanna" sort="Quer, Susanna" uniqKey="Quer S" first="Susanna" last="Quer">Susanna Quer</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Martin, Maria Carmen" sort="Martin, Maria Carmen" uniqKey="Martin M" first="Maria Carmen" last="Martín">Maria Carmen Martín</name>
<affiliation wicri:level="1"><nlm:affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Campins, Magda" sort="Campins, Magda" uniqKey="Campins M" first="Magda" last="Campins">Magda Campins</name>
<affiliation wicri:level="1"><nlm:affiliation>Preventive Medicine, Hospital Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Preventive Medicine, Hospital Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ferrer, Ricard" sort="Ferrer, Ricard" uniqKey="Ferrer R" first="Ricard" last="Ferrer">Ricard Ferrer</name>
<affiliation wicri:level="1"><nlm:affiliation>Intensive Care Department. Shock, Disfunció Orgànica i Ressuscitació (SODIR) Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Department. Shock, Disfunció Orgànica i Ressuscitació (SODIR) Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Almirante, Benito" sort="Almirante, Benito" uniqKey="Almirante B" first="Benito" last="Almirante">Benito Almirante</name>
<affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Department. Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Infectious Diseases Department. Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Esteban, Juan Ignacio" sort="Esteban, Juan Ignacio" uniqKey="Esteban J" first="Juan Ignacio" last="Esteban">Juan Ignacio Esteban</name>
<affiliation wicri:level="1"><nlm:affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Universitat Autònoma de Barcelona, Bellaterra</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pumarola, Tomas" sort="Pumarola, Tomas" uniqKey="Pumarola T" first="Tomás" last="Pumarola">Tomás Pumarola</name>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Universitat Autònoma de Barcelona, Bellaterra</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ant N, Andres" sort="Ant N, Andres" uniqKey="Ant N A" first="Andrés" last="Ant N">Andrés Ant N</name>
<affiliation wicri:level="1"><nlm:affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Universitat Autònoma de Barcelona, Bellaterra</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quer, Josep" sort="Quer, Josep" uniqKey="Quer J" first="Josep" last="Quer">Josep Quer</name>
<affiliation wicri:level="1"><nlm:affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
</affiliation>
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<series><title level="j">Emerging microbes & infections</title>
<idno type="eISSN">2222-1751</idno>
<imprint><date when="2020" type="published">2020</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Aged (MeSH)</term>
<term>Betacoronavirus (genetics)</term>
<term>Computational Biology (MeSH)</term>
<term>Coronavirus Infections (virology)</term>
<term>Female (MeSH)</term>
<term>Gene Deletion (MeSH)</term>
<term>Genome, Viral (genetics)</term>
<term>High-Throughput Nucleotide Sequencing (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (virology)</term>
<term>Quasispecies (genetics)</term>
<term>RNA Cleavage (MeSH)</term>
<term>Respiratory Tract Infections (virology)</term>
<term>Sequence Analysis, RNA (MeSH)</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term>
<term>Adulte d'âge moyen (MeSH)</term>
<term>Analyse de séquence d'ARN (MeSH)</term>
<term>Betacoronavirus (génétique)</term>
<term>Biologie informatique (MeSH)</term>
<term>Clivage de l'ARN (MeSH)</term>
<term>Délétion de gène (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Génome viral (génétique)</term>
<term>Humains (MeSH)</term>
<term>Infections de l'appareil respiratoire (virologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Mâle (MeSH)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (virologie)</term>
<term>Quasi-espèce (génétique)</term>
<term>Sujet âgé (MeSH)</term>
<term>Séquençage nucléotidique à haut débit (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Betacoronavirus</term>
<term>Genome, Viral</term>
<term>Quasispecies</term>
</keywords>
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<term>Glycoprotéine de spicule des coronavirus</term>
<term>Génome viral</term>
<term>Quasi-espèce</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections de l'appareil respiratoire</term>
<term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
<term>Respiratory Tract Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Computational Biology</term>
<term>Female</term>
<term>Gene Deletion</term>
<term>High-Throughput Nucleotide Sequencing</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Pandemics</term>
<term>RNA Cleavage</term>
<term>Sequence Analysis, RNA</term>
</keywords>
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<term>Adulte d'âge moyen</term>
<term>Analyse de séquence d'ARN</term>
<term>Biologie informatique</term>
<term>Clivage de l'ARN</term>
<term>Délétion de gène</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Pandémies</term>
<term>Sujet âgé</term>
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<front><div type="abstract" xml:lang="en">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 <i>S</i>
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.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32752979</PMID>
<DateCompleted><Year>2020</Year>
<Month>09</Month>
<Day>08</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>09</Month>
<Day>08</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2222-1751</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>9</Volume>
<Issue>1</Issue>
<PubDate><Year>2020</Year>
<Month>Dec</Month>
</PubDate>
</JournalIssue>
<Title>Emerging microbes & infections</Title>
<ISOAbbreviation>Emerg Microbes Infect</ISOAbbreviation>
</Journal>
<ArticleTitle>Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.</ArticleTitle>
<Pagination><MedlinePgn>1900-1911</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1080/22221751.2020.1806735</ELocationID>
<Abstract><AbstractText>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 <i>S</i>
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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Andrés</LastName>
<ForeName>Cristina</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Garcia-Cehic</LastName>
<ForeName>Damir</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gregori</LastName>
<ForeName>Josep</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0002-4253-8015</Identifier>
<AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Roche Diagnostics SL, Sant Cugat del Valles, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Piñana</LastName>
<ForeName>Maria</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rodriguez-Frias</LastName>
<ForeName>Francisco</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Biochemistry and Microbiology Departments, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Guerrero-Murillo</LastName>
<ForeName>Mercedes</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Esperalba</LastName>
<ForeName>Juliana</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rando</LastName>
<ForeName>Ariadna</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Goterris</LastName>
<ForeName>Lidia</ForeName>
<Initials>L</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0003-1471-4461</Identifier>
<AffiliationInfo><Affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Codina</LastName>
<ForeName>Maria Gema</ForeName>
<Initials>MG</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0002-5313-5086</Identifier>
<AffiliationInfo><Affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Quer</LastName>
<ForeName>Susanna</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Martín</LastName>
<ForeName>Maria Carmen</ForeName>
<Initials>MC</Initials>
<AffiliationInfo><Affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Campins</LastName>
<ForeName>Magda</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0002-8841-6195</Identifier>
<AffiliationInfo><Affiliation>Preventive Medicine, Hospital Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ferrer</LastName>
<ForeName>Ricard</ForeName>
<Initials>R</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0002-4859-4747</Identifier>
<AffiliationInfo><Affiliation>Intensive Care Department. Shock, Disfunció Orgànica i Ressuscitació (SODIR) Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Almirante</LastName>
<ForeName>Benito</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Infectious Diseases Department. Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Esteban</LastName>
<ForeName>Juan Ignacio</ForeName>
<Initials>JI</Initials>
<AffiliationInfo><Affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pumarola</LastName>
<ForeName>Tomás</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0002-5171-7461</Identifier>
<AffiliationInfo><Affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Antón</LastName>
<ForeName>Andrés</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0002-1476-0815</Identifier>
<AffiliationInfo><Affiliation>Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Quer</LastName>
<ForeName>Josep</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0003-0014-084X</Identifier>
<AffiliationInfo><Affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
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</PublicationTypeList>
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<MedlineTA>Emerg Microbes Infect</MedlineTA>
<NlmUniqueID>101594885</NlmUniqueID>
<ISSNLinking>2222-1751</ISSNLinking>
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<NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance>
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<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="N">deletions</Keyword>
<Keyword MajorTopicYN="N">diversity</Keyword>
<Keyword MajorTopicYN="N">quasispecies</Keyword>
<Keyword MajorTopicYN="N">respiratory virus</Keyword>
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<ArticleId IdType="doi">10.1080/22221751.2020.1806735</ArticleId>
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