SrasV1, Main, Merge, bibRecord, 003721

Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain▿

Identifieur interne : 003721 ( Main/Merge ); précédent : 003720; suivant : 003722

Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain▿

Auteurs : Marc G. Wathelet ; Melissa Orr ; Matthew B. Frieman ; Ralph S. Baric

Source :

Journal of Virology [ 0022-538X ] ; 2007.

RBID : PMC:2168762

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.
- Animaux, Cellules Vero, Clonage moléculaire, Gènes rapporteurs, Humains, Lignée cellulaire, Modèles génétiques, Régions promotrices (génétique), Résistance virale aux médicaments.

English descriptors

KwdEn :
- Animals, Antiviral Agents (pharmacology), Cell Line, Chlorocebus aethiops, Cloning, Molecular, 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).
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 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 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 nsp1 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, nsp1 is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168762

DOI: 10.1128/JVI.00702-07
PubMed: 17715225
PubMed Central: 2168762

Links to Exploration step

PMC:2168762

Le document en format XML

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<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>Interferon-beta (metabolism)</term>
<term>Interferons (metabolism)</term>
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<term>Promoter Regions, Genetic</term>
<term>RNA Replicase (metabolism)</term>
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<term>SARS Virus (pathogenicity)</term>
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<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>
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<term>Virus du SRAS (pathogénicité)</term>
<term>Virus du SRAS (physiologie)</term>
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<term>Viral Nonstructural Proteins</term>
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<term>Interférons</term>
<term>Protéines virales non structurales</term>
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<term>Chlorocebus aethiops</term>
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<term>Drug Resistance, Viral</term>
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<term>Humans</term>
<term>Models, Genetic</term>
<term>Promoter Regions, Genetic</term>
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<term>Cellules Vero</term>
<term>Clonage moléculaire</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
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<front><div type="abstract" xml:lang="en"><p>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 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 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 nsp1 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, nsp1 is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.</p>
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Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain▿

Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain▿

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

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