The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species
Identifieur interne : 000C18 ( Main/Exploration ); précédent : 000C17; suivant : 000C19The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species
Auteurs : Daniela Niemeyer [Allemagne] ; Kirstin Mösbauer [Allemagne] ; Eva M. Klein [Allemagne] ; Andrea Sieberg [Allemagne] ; Robert C. Mettelman [États-Unis] ; Anna M. Mielech [États-Unis] ; Ronald Dijkman [Suisse] ; Susan C. Baker [États-Unis] ; Christian Drosten [Allemagne] ; Marcel A. Müller [Allemagne]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Cellules HEK293, Cellules Vero, Chiroptera (virologie), Cysteine endopeptidases (génétique), Cysteine endopeptidases (physiologie), Humains, Interactions hôte-pathogène, Interférons (antagonistes et inhibiteurs), Phylogénie, Protéines virales (génétique), Protéines virales (physiologie), Réplication virale (génétique), Réplication virale (physiologie), Réservoirs d'agents pathogènes (virologie), Similitude de séquences d'acides aminés, Spécificité d'hôte, Syndrome respiratoire aigu sévère (virologie), Syndrome respiratoire aigu sévère (épidémiologie), Séquence d'acides aminés, Ubiquitine (métabolisme), Virulence (génétique), Virulence (physiologie), Virus du SRAS (enzymologie), Virus du SRAS (génétique), Virus du SRAS (pathogénicité), Zoonoses (virologie), Zoonoses (épidémiologie).
- MESH :
- antagonistes et inhibiteurs : Interférons.
- enzymologie : Virus du SRAS.
- génétique : Cysteine endopeptidases, Protéines virales, Réplication virale, Virulence, Virus du SRAS.
- métabolisme : Ubiquitine.
- pathogénicité : Virus du SRAS.
- physiologie : Cysteine endopeptidases, Protéines virales, Réplication virale, Virulence.
- virologie : Chiroptera, Réservoirs d'agents pathogènes, Syndrome respiratoire aigu sévère, Zoonoses.
- épidémiologie : Syndrome respiratoire aigu sévère, Zoonoses.
- Animaux, Cellules HEK293, Cellules Vero, Humains, Interactions hôte-pathogène, Phylogénie, Similitude de séquences d'acides aminés, Spécificité d'hôte, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Chiroptera (virology), Chlorocebus aethiops, Cysteine Endopeptidases (genetics), Cysteine Endopeptidases (physiology), Disease Reservoirs (virology), HEK293 Cells, Host Specificity, Host-Pathogen Interactions, Humans, Interferons (antagonists & inhibitors), Phylogeny, SARS Virus (enzymology), SARS Virus (genetics), SARS Virus (pathogenicity), Sequence Homology, Amino Acid, Severe Acute Respiratory Syndrome (epidemiology), Severe Acute Respiratory Syndrome (virology), Ubiquitin (metabolism), Vero Cells, Viral Proteins (genetics), Viral Proteins (physiology), Virulence (genetics), Virulence (physiology), Virus Replication (genetics), Virus Replication (physiology), Zoonoses (epidemiology), Zoonoses (virology).
- MESH :
- chemical , antagonists & inhibitors : Interferons.
- chemical , genetics : Cysteine Endopeptidases, Viral Proteins.
- chemical , metabolism : Ubiquitin.
- chemical , physiology : Cysteine Endopeptidases, Viral Proteins.
- enzymology : SARS Virus.
- epidemiology : Severe Acute Respiratory Syndrome, Zoonoses.
- genetics : SARS Virus, Virulence, Virus Replication.
- pathogenicity : SARS Virus.
- physiology : Virulence, Virus Replication.
- virology : Chiroptera, Disease Reservoirs, Severe Acute Respiratory Syndrome, Zoonoses.
- Amino Acid Sequence, Animals, Chlorocebus aethiops, HEK293 Cells, Host Specificity, Host-Pathogen Interactions, Humans, Phylogeny, Sequence Homology, Amino Acid, Vero Cells.
Abstract
SARS-coronavirus (CoV) is a zoonotic agent derived from rhinolophid bats, in which a plethora of SARS-related, conspecific viral lineages exist. Whereas the variability of virulence among reservoir-borne viruses is unknown, it is generally assumed that the emergence of epidemic viruses from animal reservoirs requires human adaptation. To understand the influence of a viral factor in relation to interspecies spillover, we studied the papain-like protease (PLP) of SARS-CoV. This key enzyme drives the early stages of infection as it cleaves the viral polyprotein, deubiquitinates viral and cellular proteins, and antagonizes the interferon (IFN) response. We identified a bat SARS-CoV PLP, which shared 86% amino acid identity with SARS-CoV PLP, and used reverse genetics to insert it into the SARS-CoV genome. The resulting virus replicated like SARS-CoV in Vero cells but was suppressed in IFN competent MA-104 (3.7-fold), Calu-3 (2.6-fold) and human airway epithelial cells (10.3-fold). Using ectopically-expressed PLP variants as well as full SARS-CoV infectious clones chimerized for PLP, we found that a protease-independent, anti-IFN function exists in SARS-CoV, but not in a SARS-related, bat-borne virus. This PLP-mediated anti-IFN difference was seen in primate, human as well as bat cells, thus independent of the host context. The results of this study revealed that coronavirus PLP confers a variable virulence trait among members of the species SARS-CoV, and that a SARS-CoV lineage with virulent PLPs may have pre-existed in the reservoir before onset of the epidemic.
Url:
DOI: 10.1371/journal.ppat.1007296
PubMed: 30248143
PubMed Central: 6171950
Affiliations:
- Allemagne, Suisse, États-Unis
- Berlin, Canton de Berne, District de Cologne, Illinois, Rhénanie-du-Nord-Westphalie
- Berlin, Berne, Bonn, Chicago
- Université de Berne, Université de Chicago
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Le document en format XML
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Müller</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, University of Bonn Medical Centre, Bonn</wicri:regionArea><placeName><region type="land" 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Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, University of Bonn Medical Centre, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>German Centre for Infection Research, associated partner Charité, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research, associated partner Charité, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Mosbauer, Kirstin" sort="Mosbauer, Kirstin" uniqKey="Mosbauer K" first="Kirstin" last="Mösbauer">Kirstin Mösbauer</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Klein, Eva M" sort="Klein, Eva M" uniqKey="Klein E" first="Eva M." last="Klein">Eva M. Klein</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, University of Bonn Medical Centre, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Sieberg, Andrea" sort="Sieberg, Andrea" uniqKey="Sieberg A" first="Andrea" last="Sieberg">Andrea Sieberg</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, University of Bonn Medical Centre, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Mettelman, Robert C" sort="Mettelman, Robert C" uniqKey="Mettelman R" first="Robert C." last="Mettelman">Robert C. Mettelman</name><affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Mielech, Anna M" sort="Mielech, Anna M" uniqKey="Mielech A" first="Anna M." last="Mielech">Anna M. Mielech</name><affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Dijkman, Ronald" sort="Dijkman, Ronald" uniqKey="Dijkman R" first="Ronald" last="Dijkman">Ronald Dijkman</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Institute of Virology and Immunology, Bern & Mittelhäusern, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Virology and Immunology, Bern & Mittelhäusern</wicri:regionArea><wicri:noRegion>Bern & Mittelhäusern</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff006"><addr-line>Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Infectious Diseases and Pathobiology, University of Bern, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName><orgName type="university">Université de Berne</orgName></affiliation></author><author><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C." last="Baker">Susan C. Baker</name><affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Loyola University of Chicago, Maywood, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, University of Bonn Medical Centre, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>German Centre for Infection Research, associated partner Charité, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research, associated partner Charité, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, University of Bonn Medical Centre, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>German Centre for Infection Research, associated partner Charité, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research, associated partner Charité, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Chiroptera (virology)</term><term>Chlorocebus aethiops</term><term>Cysteine Endopeptidases (genetics)</term><term>Cysteine Endopeptidases (physiology)</term><term>Disease Reservoirs (virology)</term><term>HEK293 Cells</term><term>Host Specificity</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Interferons (antagonists & inhibitors)</term><term>Phylogeny</term><term>SARS Virus (enzymology)</term><term>SARS Virus (genetics)</term><term>SARS Virus (pathogenicity)</term><term>Sequence Homology, Amino Acid</term><term>Severe Acute Respiratory Syndrome (epidemiology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Ubiquitin (metabolism)</term><term>Vero Cells</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (physiology)</term><term>Virulence (genetics)</term><term>Virulence (physiology)</term><term>Virus Replication (genetics)</term><term>Virus Replication (physiology)</term><term>Zoonoses (epidemiology)</term><term>Zoonoses (virology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Chiroptera (virologie)</term><term>Cysteine endopeptidases (génétique)</term><term>Cysteine endopeptidases (physiologie)</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Interférons (antagonistes et inhibiteurs)</term><term>Phylogénie</term><term>Protéines virales (génétique)</term><term>Protéines virales (physiologie)</term><term>Réplication virale (génétique)</term><term>Réplication virale (physiologie)</term><term>Réservoirs d'agents pathogènes (virologie)</term><term>Similitude de séquences d'acides aminés</term><term>Spécificité d'hôte</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Syndrome respiratoire aigu sévère (épidémiologie)</term><term>Séquence d'acides aminés</term><term>Ubiquitine (métabolisme)</term><term>Virulence (génétique)</term><term>Virulence (physiologie)</term><term>Virus du SRAS (enzymologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (pathogénicité)</term><term>Zoonoses (virologie)</term><term>Zoonoses (épidémiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interferons</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Ubiquitin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term><term>Zoonoses</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term><term>Virulence</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term><term>Réplication virale</term><term>Virulence</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Ubiquitine</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term><term>Réplication virale</term><term>Virulence</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Virulence</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Chiroptera</term><term>Réservoirs d'agents pathogènes</term><term>Syndrome respiratoire aigu sévère</term><term>Zoonoses</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Chiroptera</term><term>Disease Reservoirs</term><term>Severe Acute Respiratory Syndrome</term><term>Zoonoses</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term><term>Zoonoses</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Chlorocebus aethiops</term><term>HEK293 Cells</term><term>Host Specificity</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Phylogeny</term><term>Sequence Homology, Amino Acid</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Phylogénie</term><term>Similitude de séquences d'acides aminés</term><term>Spécificité d'hôte</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>SARS-coronavirus (CoV) is a zoonotic agent derived from rhinolophid bats, in which a plethora of SARS-related, conspecific viral lineages exist. Whereas the variability of virulence among reservoir-borne viruses is unknown, it is generally assumed that the emergence of epidemic viruses from animal reservoirs requires human adaptation. To understand the influence of a viral factor in relation to interspecies spillover, we studied the papain-like protease (PLP) of SARS-CoV. This key enzyme drives the early stages of infection as it cleaves the viral polyprotein, deubiquitinates viral and cellular proteins, and antagonizes the interferon (IFN) response. We identified a bat SARS-CoV PLP, which shared 86% amino acid identity with SARS-CoV PLP, and used reverse genetics to insert it into the SARS-CoV genome. The resulting virus replicated like SARS-CoV in Vero cells but was suppressed in IFN competent MA-104 (3.7-fold), Calu-3 (2.6-fold) and human airway epithelial cells (10.3-fold). Using ectopically-expressed PLP variants as well as full SARS-CoV infectious clones chimerized for PLP, we found that a protease-independent, anti-IFN function exists in SARS-CoV, but not in a SARS-related, bat-borne virus. This PLP-mediated anti-IFN difference was seen in primate, human as well as bat cells, thus independent of the host context. The results of this study revealed that coronavirus PLP confers a variable virulence trait among members of the species SARS-CoV, and that a SARS-CoV lineage with virulent PLPs may have pre-existed in the reservoir before onset of the epidemic.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Vijgen, L" uniqKey="Vijgen L">L Vijgen</name></author><author><name sortKey="Keyaerts, E" uniqKey="Keyaerts E">E Keyaerts</name></author><author><name sortKey="Lemey, P" uniqKey="Lemey P">P Lemey</name></author><author><name sortKey="Maes, P" uniqKey="Maes P">P Maes</name></author><author><name sortKey="Van Reeth, K" uniqKey="Van Reeth K">K Van Reeth</name></author><author><name sortKey="Nauwynck, H" uniqKey="Nauwynck H">H Nauwynck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijgen, L" uniqKey="Vijgen L">L Vijgen</name></author><author><name sortKey="Keyaerts, E" uniqKey="Keyaerts E">E 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Meng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cornish Bowden, A" uniqKey="Cornish Bowden A">A Cornish-Bowden</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Suisse</li><li>États-Unis</li></country><region><li>Berlin</li><li>Canton de Berne</li><li>District de Cologne</li><li>Illinois</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Berlin</li><li>Berne</li><li>Bonn</li><li>Chicago</li></settlement><orgName><li>Université de Berne</li><li>Université de Chicago</li></orgName></list><tree><country name="Allemagne"><region name="Berlin"><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name></region><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Klein, Eva M" sort="Klein, Eva M" uniqKey="Klein E" first="Eva M." last="Klein">Eva M. Klein</name><name sortKey="Mosbauer, Kirstin" sort="Mosbauer, Kirstin" uniqKey="Mosbauer K" first="Kirstin" last="Mösbauer">Kirstin Mösbauer</name><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><name sortKey="Sieberg, Andrea" sort="Sieberg, Andrea" uniqKey="Sieberg A" first="Andrea" last="Sieberg">Andrea Sieberg</name><name sortKey="Sieberg, Andrea" sort="Sieberg, Andrea" uniqKey="Sieberg A" first="Andrea" last="Sieberg">Andrea Sieberg</name></country><country name="États-Unis"><region name="Illinois"><name sortKey="Mettelman, Robert C" sort="Mettelman, Robert C" uniqKey="Mettelman R" first="Robert C." last="Mettelman">Robert C. Mettelman</name></region><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C." last="Baker">Susan C. Baker</name><name sortKey="Mielech, Anna M" sort="Mielech, Anna M" uniqKey="Mielech A" first="Anna M." last="Mielech">Anna M. Mielech</name></country><country name="Suisse"><noRegion><name sortKey="Dijkman, Ronald" sort="Dijkman, Ronald" uniqKey="Dijkman R" first="Ronald" last="Dijkman">Ronald Dijkman</name></noRegion><name sortKey="Dijkman, Ronald" sort="Dijkman, Ronald" uniqKey="Dijkman R" first="Ronald" last="Dijkman">Ronald Dijkman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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