Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival
Identifieur interne : 001628 ( Main/Exploration ); précédent : 001627; suivant : 001629Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival
Auteurs : Marta L. Dediego [Espagne] ; Jose L. Nieto-Torres [Espagne] ; Jose A. Regla-Nava [Espagne] ; Jose M. Jimenez-Guarde O [Espagne] ; Raul Fernandez-Delgado [Espagne] ; Craig Fett [États-Unis] ; Carlos Casta O-Rodriguez [Espagne] ; Stanley Perlman [États-Unis] ; Luis Enjuanes [Espagne]Source :
- Journal of Virology [ 0022-538X ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Cytokines (génétique), Cytokines (immunologie), Facteur de transcription NF-kappa B (génétique), Facteur de transcription NF-kappa B (immunologie), Femelle, Humains, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Régulation négative, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (génétique), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (mortalité), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (génétique), Virus du SRAS (physiologie).
- MESH :
- génétique : Cytokines, Facteur de transcription NF-kappa B, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Virus du SRAS.
- immunologie : Cytokines, Facteur de transcription NF-kappa B, Syndrome respiratoire aigu sévère.
- mortalité : Syndrome respiratoire aigu sévère.
- métabolisme : Protéines de l'enveloppe virale.
- physiologie : Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Femelle, Humains, Régulation négative, Souris, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Animals, Cytokines (genetics), Cytokines (immunology), Down-Regulation, Female, Humans, Mice, Mice, Inbred BALB C, NF-kappa B (genetics), NF-kappa B (immunology), SARS Virus (genetics), SARS Virus (physiology), Severe Acute Respiratory Syndrome (genetics), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (mortality), Severe Acute Respiratory Syndrome (virology), Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , genetics : Cytokines, NF-kappa B, Viral Envelope Proteins.
- chemical , immunology : Cytokines, NF-kappa B.
- genetics : SARS Virus, Severe Acute Respiratory Syndrome.
- immunology : Severe Acute Respiratory Syndrome.
- chemical , metabolism : Viral Envelope Proteins.
- mortality : Severe Acute Respiratory Syndrome.
- physiology : SARS Virus.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Down-Regulation, Female, Humans, Mice, Mice, Inbred BALB C.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a respiratory disease that has a 10% mortality rate. We previously showed that SARS-CoV lacking the E gene (SARS-CoV-ΔE) is attenuated in several animal model systems. Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.
Url:
DOI: 10.1128/JVI.02576-13
PubMed: 24198408
PubMed Central: 3911641
Affiliations:
- Espagne, États-Unis
- Communauté de Madrid, Iowa
- Iowa City, Madrid
- Université autonome de Madrid, Université de l'Iowa
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Le document en format XML
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Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. 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Nieto-Torres</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Regla Nava, Jose A" sort="Regla Nava, Jose A" uniqKey="Regla Nava J" first="Jose A." last="Regla-Nava">Jose A. Regla-Nava</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Jimenez Guarde O, Jose M" sort="Jimenez Guarde O, Jose M" uniqKey="Jimenez Guarde O J" first="Jose M." last="Jimenez-Guarde O">Jose M. Jimenez-Guarde O</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff><country 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O Rodriguez, Carlos" sort="Casta O Rodriguez, Carlos" uniqKey="Casta O Rodriguez C" first="Carlos" last="Casta O-Rodriguez">Carlos Casta O-Rodriguez</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:aff id="aff2">Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cytokines (genetics)</term><term>Cytokines (immunology)</term><term>Down-Regulation</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>NF-kappa B (genetics)</term><term>NF-kappa B (immunology)</term><term>SARS Virus (genetics)</term><term>SARS Virus (physiology)</term><term>Severe Acute Respiratory Syndrome (genetics)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (mortality)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cytokines (génétique)</term><term>Cytokines (immunologie)</term><term>Facteur de transcription NF-kappa B (génétique)</term><term>Facteur de transcription NF-kappa B (immunologie)</term><term>Femelle</term><term>Humains</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Régulation négative</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère (génétique)</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (mortalité)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cytokines</term><term>NF-kappa B</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Cytokines</term><term>NF-kappa B</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cytokines</term><term>Facteur de transcription NF-kappa B</term><term>Protéines de l'enveloppe virale</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cytokines</term><term>Facteur de transcription NF-kappa B</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de l'enveloppe virale</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" qualifier="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Down-Regulation</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Régulation négative</term><term>Souris</term><term>Souris de lignée BALB C</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a respiratory disease that has a 10% mortality rate. We previously showed that SARS-CoV lacking the E gene (SARS-CoV-ΔE) is attenuated in several animal model systems. Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.</p></div></front></TEI><affiliations><list><country><li>Espagne</li><li>États-Unis</li></country><region><li>Communauté de Madrid</li><li>Iowa</li></region><settlement><li>Iowa City</li><li>Madrid</li></settlement><orgName><li>Université autonome de Madrid</li><li>Université de l'Iowa</li></orgName></list><tree><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L." last="Dediego">Marta L. Dediego</name></region><name sortKey="Casta O Rodriguez, Carlos" sort="Casta O Rodriguez, Carlos" uniqKey="Casta O Rodriguez C" first="Carlos" last="Casta O-Rodriguez">Carlos Casta O-Rodriguez</name><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name><name sortKey="Jimenez Guarde O, Jose M" sort="Jimenez Guarde O, Jose M" uniqKey="Jimenez Guarde O J" first="Jose M." last="Jimenez-Guarde O">Jose M. Jimenez-Guarde O</name><name sortKey="Nieto Torres, Jose L" sort="Nieto Torres, Jose L" uniqKey="Nieto Torres J" first="Jose L." last="Nieto-Torres">Jose L. Nieto-Torres</name><name sortKey="Regla Nava, Jose A" sort="Regla Nava, Jose A" uniqKey="Regla Nava J" first="Jose A." last="Regla-Nava">Jose A. Regla-Nava</name></country><country name="États-Unis"><region name="Iowa"><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name></region><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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