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Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.

Identifieur interne : 000412 ( Main/Exploration ); précédent : 000411; suivant : 000413

Naturally 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 :

RBID : pubmed:32752979

Descripteurs français

English descriptors

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


Affiliations:


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Le document en format XML

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<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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<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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<name sortKey="Rando, Ariadna" sort="Rando, Ariadna" uniqKey="Rando A" first="Ariadna" last="Rando">Ariadna Rando</name>
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<nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
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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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<nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
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<wicri:regionArea>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
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<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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<nlm:affiliation>Microbiology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
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<name sortKey="Quer, Susanna" sort="Quer, Susanna" uniqKey="Quer S" first="Susanna" last="Quer">Susanna Quer</name>
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<settlement type="city">Barcelone</settlement>
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<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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<settlement type="city">Barcelone</settlement>
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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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<nlm:affiliation>Preventive Medicine, Hospital Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
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<wicri:regionArea>Preventive Medicine, Hospital Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
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<name sortKey="Ferrer, Ricard" sort="Ferrer, Ricard" uniqKey="Ferrer R" first="Ricard" last="Ferrer">Ricard Ferrer</name>
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<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>
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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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<wicri:regionArea>Infectious Diseases Department. Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona</wicri:regionArea>
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<settlement type="city">Barcelone</settlement>
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<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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<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>
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<settlement type="city">Barcelone</settlement>
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<wicri:regionArea>Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
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<name sortKey="Pumarola, Tomas" sort="Pumarola, Tomas" uniqKey="Pumarola T" first="Tomás" last="Pumarola">Tomás Pumarola</name>
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<nlm:affiliation>Universitat Autònoma de Barcelona, Bellaterra, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
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<settlement type="city">Barcelone</settlement>
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<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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<settlement type="city">Barcelone</settlement>
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<settlement type="city">Barcelone</settlement>
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<name sortKey="Quer, Josep" sort="Quer, Josep" uniqKey="Quer J" first="Josep" last="Quer">Josep Quer</name>
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<nlm:affiliation>Liver Unit, Liver Diseases - Viral Hepatitis, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Barcelona, Spain.</nlm:affiliation>
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<title level="j">Emerging microbes & infections</title>
<idno type="eISSN">2222-1751</idno>
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<date when="2020" type="published">2020</date>
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<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>
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<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>
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<term>Spike Glycoprotein, Coronavirus</term>
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<term>Pneumopathie virale</term>
</keywords>
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<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
<term>Respiratory Tract Infections</term>
</keywords>
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<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>
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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>
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<DateCompleted>
<Year>2020</Year>
<Month>09</Month>
<Day>08</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>09</Month>
<Day>08</Day>
</DateRevised>
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<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>
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<MedlinePgn>1900-1911</MedlinePgn>
</Pagination>
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<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>
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<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>
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<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>
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<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>
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   |texte=   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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