MersV1, PubMed, Checkpoint, bibRecord, 001241

A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

Identifieur interne : 001241 ( PubMed/Checkpoint ); précédent : 001240; suivant : 001242

A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

Auteurs : Adam S. Cockrell [États-Unis] ; Boyd L. Yount [États-Unis] ; Trevor Scobey [États-Unis] ; Kara Jensen [États-Unis] ; Madeline Douglas [États-Unis] ; Anne Beall [États-Unis] ; Xian-Chun Tang [États-Unis] ; Wayne A. Marasco [États-Unis] ; Mark T. Heise [États-Unis] ; Ralph S. Baric [États-Unis]

Source :

Nature microbiology [ 2058-5276 ] ; 2016.

RBID : pubmed:27892925

Descripteurs français

KwdFr :
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement), Dipeptidyl peptidase 4 (génétique), Dipeptidyl peptidase 4 (métabolisme), Infections à coronavirus (), Modèles animaux de maladie humaine, Organismes génétiquement modifiés, Protéines mutantes (génétique), Protéines mutantes (métabolisme), Recombinaison génétique, Récepteurs viraux (génétique), Récepteurs viraux (métabolisme), Souris, Syndrome de détresse respiratoire de l'adulte (anatomopathologie), Édition de gène.
MESH :
- anatomopathologie : Syndrome de détresse respiratoire de l'adulte.
- croissance et développement : Coronavirus du syndrome respiratoire du Moyen-Orient.
- génétique : Dipeptidyl peptidase 4, Protéines mutantes, Récepteurs viraux.
- métabolisme : Dipeptidyl peptidase 4, Protéines mutantes, Récepteurs viraux.
- Animaux, Infections à coronavirus, Modèles animaux de maladie humaine, Organismes génétiquement modifiés, Recombinaison génétique, Souris, Édition de gène.

English descriptors

KwdEn :
- Animals, Coronavirus Infections (complications), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Disease Models, Animal, Gene Editing, Mice, Middle East Respiratory Syndrome Coronavirus (growth & development), Mutant Proteins (genetics), Mutant Proteins (metabolism), Organisms, Genetically Modified, Receptors, Virus (genetics), Receptors, Virus (metabolism), Recombination, Genetic, Respiratory Distress Syndrome, Adult (pathology).
MESH :
- chemical , genetics : Dipeptidyl Peptidase 4, Mutant Proteins, Receptors, Virus.
- complications : Coronavirus Infections.
- growth & development : Middle East Respiratory Syndrome Coronavirus.
- chemical , metabolism : Dipeptidyl Peptidase 4, Mutant Proteins, Receptors, Virus.
- pathology : Respiratory Distress Syndrome, Adult.
- Animals, Disease Models, Animal, Gene Editing, Mice, Organisms, Genetically Modified, Recombination, Genetic.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

DOI: 10.1038/nmicrobiol.2016.226
PubMed: 27892925

Affiliations:

États-Unis

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Le document en format XML

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<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Disease Models, Animal</term>
<term>Gene Editing</term>
<term>Mice</term>
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<term>Dipeptidyl peptidase 4 (métabolisme)</term>
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.</div>
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<Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.</AbstractText>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cockrell</LastName>
<ForeName>Adam S</ForeName>
<Initials>AS</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.</Affiliation>
</AffiliationInfo>
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<ForeName>Boyd L</ForeName>
<Initials>BL</Initials>
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</AffiliationInfo>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Jensen</LastName>
<ForeName>Kara</ForeName>
<Initials>K</Initials>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Douglas</LastName>
<ForeName>Madeline</ForeName>
<Initials>M</Initials>
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A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

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