Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection
Identifieur interne : 002F34 ( Main/Exploration ); précédent : 002F33; suivant : 002F35Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection
Auteurs : Barry Rockx [États-Unis] ; Tracey Baas [États-Unis] ; Gregory A. Zornetzer [États-Unis] ; Bart Haagmans [Pays-Bas] ; Timothy Sheahan [États-Unis] ; Matthew Frieman [États-Unis] ; Matthew D. Dyer [États-Unis] ; Thomas H. Teal [États-Unis] ; Sean Proll [États-Unis] ; Judith Van Den Brand [Pays-Bas] ; Ralph Baric [États-Unis] ; Michael G. Katze [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Cytokines (génétique), Cytokines (immunologie), Expression des gènes, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Humains, Modèles animaux de maladie humaine, Mort, Poumon (anatomopathologie), Poumon (immunologie), Protéines de l'enveloppe virale (immunologie), Régulation positive, Souris, Souris de lignée BALB C, Syndrome de détresse respiratoire de l'adulte (génétique), Syndrome de détresse respiratoire de l'adulte (immunologie), Syndrome de détresse respiratoire de l'adulte (mortalité), Syndrome de détresse respiratoire de l'adulte (virologie), Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (génétique), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Vieillissement (immunologie), Virus du SRAS (immunologie), Virus du SRAS (isolement et purification), Virus du SRAS (physiologie).
- MESH :
- anatomopathologie : Poumon.
- génétique : Cytokines, Syndrome de détresse respiratoire de l'adulte, Syndrome respiratoire aigu sévère.
- immunologie : Cytokines, Glycoprotéines membranaires, Poumon, Protéines de l'enveloppe virale, Syndrome de détresse respiratoire de l'adulte, Syndrome respiratoire aigu sévère, Vieillissement, Virus du SRAS.
- isolement et purification : Virus du SRAS.
- mortalité : Syndrome de détresse respiratoire de l'adulte.
- physiologie : Virus du SRAS.
- virologie : Syndrome de détresse respiratoire de l'adulte, Syndrome respiratoire aigu sévère.
- Pascal (Inist)
- Animaux, Coronavirus, Aigu, Détresse respiratoire, Cytokine, Expression des gènes, Femelle, Glycoprotéine de spicule des coronavirus, Humains, Modèle animal, Infection, Modèles animaux de maladie humaine, Mort, Régulation positive, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère, Virologie, Syndrome respiratoire aigu sévère, Association genetique.
English descriptors
- KwdEn :
- Acute, Aging (immunology), Animal model, Animals, Coronavirus, Cytokine, Cytokines (genetics), Cytokines (immunology), Death, Disease Models, Animal, Female, Gene Expression, Humans, Infection, Lung (immunology), Lung (pathology), Membrane Glycoproteins (immunology), Mice, Mice, Inbred BALB C, Respiratory Distress Syndrome, Adult (genetics), Respiratory Distress Syndrome, Adult (immunology), Respiratory Distress Syndrome, Adult (mortality), Respiratory Distress Syndrome, Adult (virology), Respiratory distress, SARS Virus (immunology), SARS Virus (isolation & purification), SARS Virus (physiology), Severe Acute Respiratory Syndrome (complications), Severe Acute Respiratory Syndrome (genetics), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Severe acute respiratory syndrome, Spike Glycoprotein, Coronavirus, Up-Regulation, Viral Envelope Proteins (immunology), Virology.
- MESH :
- chemical , genetics : Cytokines.
- complications : Severe Acute Respiratory Syndrome.
- genetics : Respiratory Distress Syndrome, Adult, Severe Acute Respiratory Syndrome.
- immunology : Aging, Cytokines, Lung, Membrane Glycoproteins, Respiratory Distress Syndrome, Adult, SARS Virus, Severe Acute Respiratory Syndrome, Viral Envelope Proteins.
- isolation & purification : SARS Virus.
- mortality : Respiratory Distress Syndrome, Adult.
- pathology : Lung.
- physiology : SARS Virus.
- virology : Respiratory Distress Syndrome, Adult, Severe Acute Respiratory Syndrome.
- Animals, Death, Disease Models, Animal, Female, Gene Expression, Humans, Mice, Mice, Inbred BALB C, Spike Glycoprotein, Coronavirus, Up-Regulation.
Abstract
Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.
Url:
Affiliations:
- Pays-Bas, États-Unis
- Caroline du Nord, Hollande-Méridionale, Washington (État)
- Rotterdam, Seattle
- Université de Washington
Links toward previous steps (curation, corpus...)
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection</title>
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<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author><name sortKey="Proll, Sean" sort="Proll, Sean" uniqKey="Proll S" first="Sean" last="Proll">Sean Proll</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology, School of Medicine, University of Washington</s1>
<s2>Seattle, Washington</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author><name sortKey="Van Den Brand, Judith" sort="Van Den Brand, Judith" uniqKey="Van Den Brand J" first="Judith" last="Van Den Brand">Judith Van Den Brand</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Virology, Erasmus Medical Center</s1>
<s2>Rotterdam</s2>
<s3>NLD</s3>
<sZ>4 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Epidemiology, University of North Carolina</s1>
<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Microbiology and Immunology, University of North Carolina</s1>
<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology, School of Medicine, University of Washington</s1>
<s2>Seattle, Washington</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</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="2009">2009</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>Aging (immunology)</term>
<term>Animal model</term>
<term>Animals</term>
<term>Coronavirus</term>
<term>Cytokine</term>
<term>Cytokines (genetics)</term>
<term>Cytokines (immunology)</term>
<term>Death</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Infection</term>
<term>Lung (immunology)</term>
<term>Lung (pathology)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Respiratory Distress Syndrome, Adult (genetics)</term>
<term>Respiratory Distress Syndrome, Adult (immunology)</term>
<term>Respiratory Distress Syndrome, Adult (mortality)</term>
<term>Respiratory Distress Syndrome, Adult (virology)</term>
<term>Respiratory distress</term>
<term>SARS Virus (immunology)</term>
<term>SARS Virus (isolation & purification)</term>
<term>SARS Virus (physiology)</term>
<term>Severe Acute Respiratory Syndrome (complications)</term>
<term>Severe Acute Respiratory Syndrome (genetics)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Severe acute respiratory syndrome</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Up-Regulation</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Virology</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Cytokines (génétique)</term>
<term>Cytokines (immunologie)</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mort</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (immunologie)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Régulation positive</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome de détresse respiratoire de l'adulte (génétique)</term>
<term>Syndrome de détresse respiratoire de l'adulte (immunologie)</term>
<term>Syndrome de détresse respiratoire de l'adulte (mortalité)</term>
<term>Syndrome de détresse respiratoire de l'adulte (virologie)</term>
<term>Syndrome respiratoire aigu sévère ()</term>
<term>Syndrome respiratoire aigu sévère (génétique)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Vieillissement (immunologie)</term>
<term>Virus du SRAS (immunologie)</term>
<term>Virus du SRAS (isolement et purification)</term>
<term>Virus du SRAS (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Respiratory Distress Syndrome, Adult</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cytokines</term>
<term>Syndrome de détresse respiratoire de l'adulte</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cytokines</term>
<term>Glycoprotéines membranaires</term>
<term>Poumon</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome de détresse respiratoire de l'adulte</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Vieillissement</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Aging</term>
<term>Cytokines</term>
<term>Lung</term>
<term>Membrane Glycoproteins</term>
<term>Respiratory Distress Syndrome, Adult</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Respiratory Distress Syndrome, Adult</term>
</keywords>
<keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Syndrome de détresse respiratoire de l'adulte</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</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 de détresse respiratoire de l'adulte</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Respiratory Distress Syndrome, Adult</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Death</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Coronavirus</term>
<term>Aigu</term>
<term>Détresse respiratoire</term>
<term>Cytokine</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Modèle animal</term>
<term>Infection</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mort</term>
<term>Régulation positive</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Association genetique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.</div>
</front>
</TEI>
<affiliations><list><country><li>Pays-Bas</li>
<li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Hollande-Méridionale</li>
<li>Washington (État)</li>
</region>
<settlement><li>Rotterdam</li>
<li>Seattle</li>
</settlement>
<orgName><li>Université de Washington</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Rockx, Barry" sort="Rockx, Barry" uniqKey="Rockx B" first="Barry" last="Rockx">Barry Rockx</name>
</region>
<name sortKey="Baas, Tracey" sort="Baas, Tracey" uniqKey="Baas T" first="Tracey" last="Baas">Tracey Baas</name>
<name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name>
<name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name>
<name sortKey="Dyer, Matthew D" sort="Dyer, Matthew D" uniqKey="Dyer M" first="Matthew D." last="Dyer">Matthew D. Dyer</name>
<name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name>
<name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name>
<name sortKey="Proll, Sean" sort="Proll, Sean" uniqKey="Proll S" first="Sean" last="Proll">Sean Proll</name>
<name sortKey="Sheahan, Timothy" sort="Sheahan, Timothy" uniqKey="Sheahan T" first="Timothy" last="Sheahan">Timothy Sheahan</name>
<name sortKey="Teal, Thomas H" sort="Teal, Thomas H" uniqKey="Teal T" first="Thomas H." last="Teal">Thomas H. Teal</name>
<name sortKey="Zornetzer, Gregory A" sort="Zornetzer, Gregory A" uniqKey="Zornetzer G" first="Gregory A." last="Zornetzer">Gregory A. Zornetzer</name>
</country>
<country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Haagmans, Bart" sort="Haagmans, Bart" uniqKey="Haagmans B" first="Bart" last="Haagmans">Bart Haagmans</name>
</region>
<name sortKey="Van Den Brand, Judith" sort="Van Den Brand, Judith" uniqKey="Van Den Brand J" first="Judith" last="Van Den Brand">Judith Van Den Brand</name>
</country>
</tree>
</affiliations>
</record>
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