Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain
Identifieur interne : 003B31 ( Main/Exploration ); précédent : 003B30; suivant : 003B32Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain
Auteurs : Marc G. Wathelet [États-Unis] ; Melissa Orr [États-Unis] ; Matthew B. Frieman [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Cellules Vero, Clonage moléculaire, Gènes rapporteurs, Humains, Interféron bêta (métabolisme), Interférons (métabolisme), Lignée cellulaire, Modèles génétiques, Protéines virales non structurales (métabolisme), RNA replicase (métabolisme), Régions promotrices (génétique), Résistance virale aux médicaments, Virus du SRAS (génétique), Virus du SRAS (pathogénicité), Virus du SRAS (physiologie).
- MESH :
- génétique : Virus du SRAS.
- métabolisme : Interféron bêta, Interférons, Protéines virales non structurales, RNA replicase.
- pathogénicité : Virus du SRAS.
- pharmacologie : Antiviraux.
- physiologie : Virus du SRAS.
- Pascal (Inist)
English descriptors
- KwdEn :
- Acute, Animals, Antiviral, Antiviral Agents (pharmacology), Attenuated strain, Cell Line, Chlorocebus aethiops, Cloning, Molecular, Coronavirus, Drug Resistance, Viral, Genes, Reporter, Humans, Interferon-beta (metabolism), Interferons (metabolism), Models, Genetic, Promoter Regions, Genetic, RNA Replicase (metabolism), SARS Virus (genetics), SARS Virus (pathogenicity), SARS Virus (physiology), Vero Cells, Viral Nonstructural Proteins (metabolism), Virology.
- MESH :
- chemical , metabolism : Interferon-beta, Interferons, RNA Replicase, Viral Nonstructural Proteins.
- chemical , pharmacology : Antiviral Agents.
- genetics : SARS Virus.
- pathogenicity : SARS Virus.
- physiology : SARS Virus.
- Animals, Cell Line, Chlorocebus aethiops, Cloning, Molecular, Drug Resistance, Viral, Genes, Reporter, Humans, Models, Genetic, Promoter Regions, Genetic, Vero Cells.
Abstract
The severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV nonstructural protein 1 (nspl) and show that expression of nspl significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nspl significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1 while having little effect on those of STAT2, JAK1, and TYK2. We engineered an attenuated mutant of nspl in SARS-CoV through reverse genetics, and the resulting mutant virus was viable and replicated as efficiently as wild-type virus in cells with a defective IFN response. However, mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nspl is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.
Url:
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 000332
- to stream PascalFrancis, to step Curation: 000657
- to stream PascalFrancis, to step Checkpoint: 000340
- to stream Main, to step Merge: 003C87
- to stream Pmc, to step Corpus: 000720
- to stream Pmc, to step Curation: 000720
- to stream Pmc, to step Checkpoint: 000E93
- to stream PubMed, to step Corpus: 001D40
- to stream PubMed, to step Curation: 001D40
- to stream PubMed, to step Checkpoint: 001C94
- to stream Ncbi, to step Merge: 001A46
- to stream Ncbi, to step Curation: 001A46
- to stream Ncbi, to step Checkpoint: 001A46
- to stream Main, to step Merge: 003721
- to stream Main, to step Curation: 003B31
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain</title><author><name sortKey="Wathelet, Marc G" sort="Wathelet, Marc G" uniqKey="Wathelet M" first="Marc G." last="Wathelet">Marc G. Wathelet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way</s1><s2>Cincinnati, Ohio 45267-0576</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cincinnati, Ohio 45267-0576</wicri:noRegion></affiliation></author><author><name sortKey="Orr, Melissa" sort="Orr, Melissa" uniqKey="Orr M" first="Melissa" last="Orr">Melissa Orr</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way</s1><s2>Cincinnati, Ohio 45267-0576</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cincinnati, Ohio 45267-0576</wicri:noRegion></affiliation></author><author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Epidemiology and Microbiology and Immunolgy, University of North Carolina</s1><s2>Chapel Hill, North Carolina 27599-7435</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chapel Hill, North Carolina 27599-7435</wicri:noRegion></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Epidemiology and Microbiology and Immunolgy, University of North Carolina</s1><s2>Chapel Hill, North Carolina 27599-7435</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chapel Hill, North Carolina 27599-7435</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Carolina Vaccine Institute, University of North Carolina</s1><s2>Chapel Hill, North Carolina 27599-7435</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chapel Hill, North Carolina 27599-7435</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0500880</idno><date when="2007">2007</date><idno type="stanalyst">PASCAL 07-0500880 INIST</idno><idno type="RBID">Pascal:07-0500880</idno><idno type="wicri:Area/PascalFrancis/Corpus">000332</idno><idno type="wicri:Area/PascalFrancis/Curation">000657</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000340</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000340</idno><idno type="wicri:doubleKey">0022-538X:2007:Wathelet M:severe:acute:respiratory</idno><idno type="wicri:Area/Main/Merge">003C87</idno><idno type="wicri:source">PMC</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168762</idno><idno type="RBID">PMC:2168762</idno><idno type="wicri:Area/Pmc/Corpus">000720</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000720</idno><idno type="wicri:Area/Pmc/Curation">000720</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000720</idno><idno type="wicri:Area/Pmc/Checkpoint">000E93</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000E93</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:17715225</idno><idno type="wicri:Area/PubMed/Corpus">001D40</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001D40</idno><idno type="wicri:Area/PubMed/Curation">001D40</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001D40</idno><idno type="wicri:Area/PubMed/Checkpoint">001C94</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001C94</idno><idno type="wicri:Area/Ncbi/Merge">001A46</idno><idno type="wicri:Area/Ncbi/Curation">001A46</idno><idno type="wicri:Area/Ncbi/Checkpoint">001A46</idno><idno type="wicri:doubleKey">0022-538X:2007:Wathelet M:severe:acute:respiratory</idno><idno type="wicri:Area/Main/Merge">003721</idno><idno type="wicri:Area/Main/Curation">003B31</idno><idno type="wicri:Area/Main/Exploration">003B31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain</title><author><name sortKey="Wathelet, Marc G" sort="Wathelet, Marc G" uniqKey="Wathelet M" first="Marc G." last="Wathelet">Marc G. Wathelet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way</s1><s2>Cincinnati, Ohio 45267-0576</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cincinnati, Ohio 45267-0576</wicri:noRegion></affiliation></author><author><name sortKey="Orr, Melissa" sort="Orr, Melissa" uniqKey="Orr M" first="Melissa" last="Orr">Melissa Orr</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way</s1><s2>Cincinnati, Ohio 45267-0576</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cincinnati, Ohio 45267-0576</wicri:noRegion></affiliation></author><author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Epidemiology and Microbiology and Immunolgy, University of North Carolina</s1><s2>Chapel Hill, North Carolina 27599-7435</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chapel Hill, North Carolina 27599-7435</wicri:noRegion></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Epidemiology and Microbiology and Immunolgy, University of North Carolina</s1><s2>Chapel Hill, North Carolina 27599-7435</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chapel Hill, North Carolina 27599-7435</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Carolina Vaccine Institute, University of North Carolina</s1><s2>Chapel Hill, North Carolina 27599-7435</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chapel Hill, North Carolina 27599-7435</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute</term><term>Animals</term><term>Antiviral</term><term>Antiviral Agents (pharmacology)</term><term>Attenuated strain</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Cloning, Molecular</term><term>Coronavirus</term><term>Drug Resistance, Viral</term><term>Genes, Reporter</term><term>Humans</term><term>Interferon-beta (metabolism)</term><term>Interferons (metabolism)</term><term>Models, Genetic</term><term>Promoter Regions, Genetic</term><term>RNA Replicase (metabolism)</term><term>SARS Virus (genetics)</term><term>SARS Virus (pathogenicity)</term><term>SARS Virus (physiology)</term><term>Vero Cells</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virology</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Cellules Vero</term><term>Clonage moléculaire</term><term>Gènes rapporteurs</term><term>Humains</term><term>Interféron bêta (métabolisme)</term><term>Interférons (métabolisme)</term><term>Lignée cellulaire</term><term>Modèles génétiques</term><term>Protéines virales non structurales (métabolisme)</term><term>RNA replicase (métabolisme)</term><term>Régions promotrices (génétique)</term><term>Résistance virale aux médicaments</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (pathogénicité)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interferon-beta</term><term>Interferons</term><term>RNA Replicase</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Interféron bêta</term><term>Interférons</term><term>Protéines virales non structurales</term><term>RNA replicase</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="pharmacologie" xml:lang="fr"><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Cloning, Molecular</term><term>Drug Resistance, Viral</term><term>Genes, Reporter</term><term>Humans</term><term>Models, Genetic</term><term>Promoter Regions, Genetic</term><term>Vero Cells</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Clonage moléculaire</term><term>Coronavirus</term><term>Aigu</term><term>Antiviral</term><term>Gènes rapporteurs</term><term>Humains</term><term>Lignée cellulaire</term><term>Modèles génétiques</term><term>Régions promotrices (génétique)</term><term>Résistance virale aux médicaments</term><term>Souche atténuée</term><term>Virologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV nonstructural protein 1 (nspl) and show that expression of nspl significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nspl significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1 while having little effect on those of STAT2, JAK1, and TYK2. We engineered an attenuated mutant of nspl in SARS-CoV through reverse genetics, and the resulting mutant virus was viable and replicated as efficiently as wild-type virus in cells with a defective IFN response. However, mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nspl is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Wathelet, Marc G" sort="Wathelet, Marc G" uniqKey="Wathelet M" first="Marc G." last="Wathelet">Marc G. Wathelet</name></noRegion><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name><name sortKey="Orr, Melissa" sort="Orr, Melissa" uniqKey="Orr M" first="Melissa" last="Orr">Melissa Orr</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003B31 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003B31 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= Pascal:07-0500880
|texte= Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain
}}
| This area was generated with Dilib version V0.6.33. |  |