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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Douglas</name><affiliation wicri:level="2"><nlm:aff id="aff0005">Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Kocher, Jacob F" sort="Kocher, Jacob F" uniqKey="Kocher J" first="Jacob F." last="Kocher">Jacob F. Kocher</name><affiliation wicri:level="2"><nlm:aff id="aff0005">Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name><affiliation wicri:level="2"><nlm:aff id="aff0005">Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation wicri:level="2"><nlm:aff id="aff0005">Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff0010">Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Cockrell, Adam S" sort="Cockrell, Adam S" uniqKey="Cockrell A" first="Adam S." last="Cockrell">Adam S. Cockrell</name><affiliation wicri:level="2"><nlm:aff id="aff0005">Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><idno type="eISSN">1096-0341</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biological Evolution</term><term>Coronavirus Infections (pathology)</term><term>Coronavirus Infections (virology)</term><term>Lung (virology)</term><term>Mice</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Organisms, Genetically Modified</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (virologie)</term><term>Organismes génétiquement modifiés</term><term>Poumon (virologie)</term><term>Souris</term><term>Évolution biologique</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biological Evolution</term><term>Mice</term><term>Organisms, Genetically Modified</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Organismes génétiquement modifiés</term><term>Souris</term><term>Évolution biologique</term></keywords></textClass></profileDesc></teiHeader><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><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alsaad, K O" uniqKey="Alsaad K">K.O. Alsaad</name></author><author><name sortKey="Hajeer, A H" uniqKey="Hajeer A">A.H. Hajeer</name></author><author><name sortKey="Al Balwi, M" uniqKey="Al Balwi M">M. Al Balwi</name></author><author><name sortKey="Al Moaiqel, M" uniqKey="Al Moaiqel M">M. Al Moaiqel</name></author><author><name sortKey="Al Oudah, N" uniqKey="Al Oudah N">N. Al Oudah</name></author><author><name sortKey="Al Ajlan, A" uniqKey="Al Ajlan A">A. Al Ajlan</name></author><author><name sortKey="Aljohani, S" uniqKey="Aljohani S">S. AlJohani</name></author><author><name sortKey="Alsolamy, S" uniqKey="Alsolamy S">S. Alsolamy</name></author><author><name sortKey="Gmati, G E" uniqKey="Gmati G">G.E. 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Baric</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Cockrell, Adam S" sort="Cockrell, Adam S" uniqKey="Cockrell A" first="Adam S." last="Cockrell">Adam S. Cockrell</name><name sortKey="Kocher, Jacob F" sort="Kocher, Jacob F" uniqKey="Kocher J" first="Jacob F." last="Kocher">Jacob F. Kocher</name><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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