Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease
Identifieur interne : 000E97 ( Main/Exploration ); précédent : 000E96; suivant : 000E98Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease
Auteurs : Madeline G. Douglas [États-Unis] ; Jacob F. Kocher [États-Unis] ; Trevor Scobey [États-Unis] ; Ralph S. Baric [États-Unis] ; Adam S. Cockrell [États-Unis]Source :
- Virology [ 0042-6822 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
- anatomopathologie : Infections à coronavirus.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus, Poumon.
- Animaux, Organismes génétiquement modifiés, Souris, Évolution biologique.
English descriptors
- KwdEn :
- MESH :
- pathology : Coronavirus Infections.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections, Lung.
- Animals, Biological Evolution, Mice, Organisms, Genetically Modified.
Abstract
We recently established a mouse model (288–330+/+) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 106 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 103 and 105 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.
Url:
DOI: 10.1016/j.virol.2017.12.006
PubMed: 29277291
PubMed Central: 5869108
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>We recently established a mouse model (288–330<sup>+/+</sup>
) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 10<sup>6</sup>
PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10<sup>3</sup>
and 10<sup>5</sup>
PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.</p>
</div>
</front>
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</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
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<tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Douglas, Madeline G" sort="Douglas, Madeline G" uniqKey="Douglas M" first="Madeline G." last="Douglas">Madeline G. Douglas</name>
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