SrasV1, Main, Exploration, bibRecord, 001F74

Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

Identifieur interne : 001F74 ( Main/Exploration ); précédent : 001F73; suivant : 001F75

Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

Auteurs : Matthew Frieman [États-Unis] ; Boyd Yount [États-Unis] ; Sudhakar Agnihothram [États-Unis] ; Carly Page [États-Unis] ; Eric Donaldson [États-Unis] ; Anjeanette Roberts [États-Unis] ; Leatrice Vogel [États-Unis] ; Becky Woodruff [États-Unis] ; Diana Scorpio [États-Unis] ; Kanta Subbarao [États-Unis] ; Ralph S. Baric [États-Unis]

Source :

Journal of virology [ 0022-538X ] ; 2012.

RBID : Pascal:12-0094566

Descripteurs français

KwdFr :
- Animaux, Facteurs de l'âge, Femelle, Génétique inverse, Humains, Lignée cellulaire, Modèles animaux de maladie humaine, Mutation, Protéines virales (génétique), Protéines virales (métabolisme), Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (mortalité), Syndrome respiratoire aigu sévère (virologie), Virulence, Virus du SRAS (génétique), Virus du SRAS (isolement et purification), Virus du SRAS (métabolisme), Virus du SRAS (pathogénicité).
MESH :
- anatomopathologie : Syndrome respiratoire aigu sévère.
- génétique : Protéines virales, Virus du SRAS.
- isolement et purification : Virus du SRAS.
- mortalité : Syndrome respiratoire aigu sévère.
- métabolisme : Protéines virales, Virus du SRAS.
- pathogénicité : Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
Pascal (Inist)
- Animaux, Coronavirus, Facteurs de l'âge, Femelle, Génétique inverse, Homme, Humains, Lignée cellulaire, Modèles animaux de maladie humaine, Mutation, Pathogénie, Souris, Souris de lignée BALB C, Virulence, Modèle animal, Syndrome respiratoire aigu sévère.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Age Factors, Animal model, Animals, Cell Line, Coronavirus, Disease Models, Animal, Female, Human, Humans, Mice, Mice, Inbred BALB C, Mutation, Pathogenesis, Reverse Genetics, SARS Virus (genetics), SARS Virus (isolation & purification), SARS Virus (metabolism), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (mortality), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology), Severe acute respiratory syndrome, Viral Proteins (genetics), Viral Proteins (metabolism), Virulence.
MESH :
- chemical , genetics : Viral Proteins.
- genetics : SARS Virus.
- isolation & purification : SARS Virus.
- metabolism : SARS Virus, Viral Proteins.
- mortality : Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- pathology : Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Age Factors, Animals, Cell Line, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred BALB C, Mutation, Reverse Genetics, Virulence.

Abstract

SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255850

Affiliations:

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age Factors</term>
<term>Animal model</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Coronavirus</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Human</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mutation</term>
<term>Pathogenesis</term>
<term>Reverse Genetics</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (isolation & purification)</term>
<term>SARS Virus (metabolism)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (mortality)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Severe acute respiratory syndrome</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</term>
<term>Virulence</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Facteurs de l'âge</term>
<term>Femelle</term>
<term>Génétique inverse</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mutation</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (mortalité)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virulence</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (isolement et purification)</term>
<term>Virus du SRAS (métabolisme)</term>
<term>Virus du SRAS (pathogénicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines virales</term>
<term>Virus du SRAS</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="metabolism" xml:lang="en"><term>SARS Virus</term>
<term>Viral 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 virales</term>
<term>Virus du SRAS</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="pathology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</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>Age Factors</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mutation</term>
<term>Reverse Genetics</term>
<term>Virulence</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Coronavirus</term>
<term>Facteurs de l'âge</term>
<term>Femelle</term>
<term>Génétique inverse</term>
<term>Homme</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mutation</term>
<term>Pathogénie</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Virulence</term>
<term>Modèle animal</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en">SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Maryland</li>
</region>
<settlement><li>Chapel Hill (Caroline du Nord)</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Maryland"><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name>
</region>
<name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name>
<name sortKey="Page, Carly" sort="Page, Carly" uniqKey="Page C" first="Carly" last="Page">Carly Page</name>
<name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name>
<name sortKey="Scorpio, Diana" sort="Scorpio, Diana" uniqKey="Scorpio D" first="Diana" last="Scorpio">Diana Scorpio</name>
<name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name>
<name sortKey="Woodruff, Becky" sort="Woodruff, Becky" uniqKey="Woodruff B" first="Becky" last="Woodruff">Becky Woodruff</name>
<name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name>
</country>
</tree>
</affiliations>
</record>

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Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

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