Fitness Barriers Limit Reversion of a Proofreading-Deficient Coronavirus
Identifieur interne : 000B41 ( Main/Exploration ); précédent : 000B40; suivant : 000B42Fitness Barriers Limit Reversion of a Proofreading-Deficient Coronavirus
Auteurs : Kevin W. Graepel [États-Unis] ; Maria L. Agostini [États-Unis] ; Xiaotao Lu [États-Unis] ; Nicole R. Sexton [États-Unis] ; Mark R. Denison [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2019.
Abstract
Coronaviruses encode an exoribonuclease (ExoN) that is important for viral replication, fitness, and virulence, yet coronaviruses with a defective ExoN (ExoN-AA) have not reverted under diverse experimental conditions. In this study, we identify multiple impediments to MHV-ExoN-AA reversion. We show that ExoN-AA reversion is possible but evolutionarily unfavorable. Instead, compensatory mutations outside ExoN-AA motif I are more accessible and beneficial than partial reversion. We also show that coevolution between replicase proteins over long-term passage partially compensates for ExoN-AA motif I but renders the virus inhospitable to a reverted ExoN. Our results reveal the evolutionary basis for the genetic stability of ExoN-inactivating mutations, illuminate complex functional and evolutionary relationships between coronavirus replicase proteins, and identify potential mechanisms for stabilization of ExoN-AA coronavirus mutants.
Url:
DOI: 10.1128/JVI.00711-19
PubMed: 31341046
PubMed Central: 6798108
Affiliations:
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Sexton</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado</wicri:regionArea><placeName><region type="state">Colorado</region></placeName></affiliation></author><author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Coronaviruses encode an exoribonuclease (ExoN) that is important for viral replication, fitness, and virulence, yet coronaviruses with a defective ExoN (ExoN-AA) have not reverted under diverse experimental conditions. In this study, we identify multiple impediments to MHV-ExoN-AA reversion. We show that ExoN-AA reversion is possible but evolutionarily unfavorable. Instead, compensatory mutations outside ExoN-AA motif I are more accessible and beneficial than partial reversion. We also show that coevolution between replicase proteins over long-term passage partially compensates for ExoN-AA motif I but renders the virus inhospitable to a reverted ExoN. Our results reveal the evolutionary basis for the genetic stability of ExoN-inactivating mutations, illuminate complex functional and evolutionary relationships between coronavirus replicase proteins, and identify potential mechanisms for stabilization of ExoN-AA coronavirus mutants.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Colorado</li><li>Tennessee</li></region></list><tree><country name="États-Unis"><region name="Tennessee"><name sortKey="Graepel, Kevin W" sort="Graepel, Kevin W" uniqKey="Graepel K" first="Kevin W." last="Graepel">Kevin W. Graepel</name></region><name sortKey="Agostini, Maria L" sort="Agostini, Maria L" uniqKey="Agostini M" first="Maria L." last="Agostini">Maria L. Agostini</name><name sortKey="Agostini, Maria L" sort="Agostini, Maria L" uniqKey="Agostini M" first="Maria L." last="Agostini">Maria L. Agostini</name><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><name sortKey="Graepel, Kevin W" sort="Graepel, Kevin W" uniqKey="Graepel K" first="Kevin W." last="Graepel">Kevin W. Graepel</name><name sortKey="Lu, Xiaotao" sort="Lu, Xiaotao" uniqKey="Lu X" first="Xiaotao" last="Lu">Xiaotao Lu</name><name sortKey="Sexton, Nicole R" sort="Sexton, Nicole R" uniqKey="Sexton N" first="Nicole R." last="Sexton">Nicole R. Sexton</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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