SrasV1, PascalFrancis, Corpus, bibRecord, 000075

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

Identifieur interne : 000075 ( PascalFrancis/Corpus ); précédent : 000074; suivant : 000076

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

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

Source :

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

RBID : Pascal:12-0094566

Descripteurs français

Pascal (Inist)
- Coronavirus, Homme, Pathogénie, Virulence, Modèle animal, Syndrome respiratoire aigu sévère.

English descriptors

KwdEn :
- Animal model, Coronavirus, Human, Pathogenesis, Severe acute respiratory syndrome, 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.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A14	`01`			`@1 Department of Microbiology and Immunology, University of Maryland School of Medicine @2 Baltimore, Maryland @3 USA @Z 1 aut. @Z 4 aut.`
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C01	`01`		`ENG`	@0 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.
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Format Inist (serveur)

NO :	PASCAL 12-0094566 INIST
ET :	Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease
AU :	FRIEMAN (Matthew); YOUNT (Boyd); AGNIHOTHRAM (Sudhakar); PAGE (Carly); DONALDSON (Eric); ROBERTS (Anjeanette); VOGEL (Leatrice); WOODRUFF (Becky); SCORPIO (Diana); SUBBARAO (Kanta); BARIC (Ralph S.)
AF :	Department of Microbiology and Immunology, University of Maryland School of Medicine/Baltimore, Maryland/Etats-Unis (1 aut., 4 aut.); Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (2 aut., 3 aut., 5 aut., 8 aut., 11 aut.); Laboratory of Infectious Diseases, NIAID, NIH/Bethesda, Maryland/Etats-Unis (6 aut., 7 aut., 10 aut.); Department of Molecular and Comparative Pathology, Johns Hopkins University/Baltimore, Maryland/Etats-Unis (9 aut.)
DT :	Publication en série; Niveau analytique
SO :	Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2012; Vol. 86; No. 2; Pp. 884-897; Bibl. 75 ref.
LA :	Anglais
EA :	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.
CC :	002A05C10; 002A05C04
FD :	Coronavirus; Homme; Pathogénie; Virulence; Modèle animal; Syndrome respiratoire aigu sévère
FG :	Coronaviridae; Nidovirales; Virus; Pathologie de l'appareil respiratoire; Virose; Infection; Pathologie des poumons
ED :	Coronavirus; Human; Pathogenesis; Virulence; Animal model; Severe acute respiratory syndrome
EG :	Coronaviridae; Nidovirales; Virus; Respiratory disease; Viral disease; Infection; Lung disease
SD :	Coronavirus; Hombre; Patogenia; Virulencia; Modelo animal; Síndrome respiratorio agudo severo
LO :	INIST-13592.354000508886770220
ID :	12-0094566

Links to Exploration step

Pascal:12-0094566

Le document en format XML

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<author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name>
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<author><name sortKey="Woodruff, Becky" sort="Woodruff, Becky" uniqKey="Woodruff B" first="Becky" last="Woodruff">Becky Woodruff</name>
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<author><name sortKey="Scorpio, Diana" sort="Scorpio, Diana" uniqKey="Scorpio D" first="Diana" last="Scorpio">Diana Scorpio</name>
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<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
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<author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
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<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>
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<ET>Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease</ET>
<AU>FRIEMAN (Matthew); YOUNT (Boyd); AGNIHOTHRAM (Sudhakar); PAGE (Carly); DONALDSON (Eric); ROBERTS (Anjeanette); VOGEL (Leatrice); WOODRUFF (Becky); SCORPIO (Diana); SUBBARAO (Kanta); BARIC (Ralph S.)</AU>
<AF>Department of Microbiology and Immunology, University of Maryland School of Medicine/Baltimore, Maryland/Etats-Unis (1 aut., 4 aut.); Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (2 aut., 3 aut., 5 aut., 8 aut., 11 aut.); Laboratory of Infectious Diseases, NIAID, NIH/Bethesda, Maryland/Etats-Unis (6 aut., 7 aut., 10 aut.); Department of Molecular and Comparative Pathology, Johns Hopkins University/Baltimore, Maryland/Etats-Unis (9 aut.)</AF>
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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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