Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice
Identifieur interne : 000E77 ( Main/Exploration ); précédent : 000E76; suivant : 000E78Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice
Auteurs : Lisa E. Gralinski [États-Unis] ; Vineet D. Menachery [États-Unis] ; Andrew P. Morgan [États-Unis] ; Allison L. Totura [États-Unis] ; Anne Beall [États-Unis] ; Jacob Kocher [États-Unis] ; Jessica Plante [États-Unis] ; D. Corinne Harrison-Shostak [États-Unis] ; Alexandra Sch Fer [États-Unis] ; Fernando Pardo-Manuel De Villena [États-Unis] ; Martin T. Ferris [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- G3: Genes|Genomes|Genetics [ 2160-1836 ] ; 2017.
Descripteurs français
- KwdFr :
- Allèles, Animaux, Cartographie chromosomique, Charge virale, Femelle, Génotype, Interactions hôte-pathogène (génétique), Lignée cellulaire, Locus de caractère quantitatif, Modèles animaux de maladie humaine, Mâle, Phénotype, Prédisposition génétique à une maladie, Souris, Souris knockout, Syndrome respiratoire aigu sévère (diagnostic), Syndrome respiratoire aigu sévère (génétique), Syndrome respiratoire aigu sévère (virologie), Variation génétique, Virus du SRAS (physiologie).
- MESH :
- diagnostic : Syndrome respiratoire aigu sévère.
- génétique : Interactions hôte-pathogène, Syndrome respiratoire aigu sévère.
- physiologie : Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Allèles, Animaux, Cartographie chromosomique, Charge virale, Femelle, Génotype, Lignée cellulaire, Locus de caractère quantitatif, Modèles animaux de maladie humaine, Mâle, Phénotype, Prédisposition génétique à une maladie, Souris, Souris knockout, Variation génétique.
English descriptors
- KwdEn :
- Alleles, Animals, Cell Line, Chromosome Mapping, Disease Models, Animal, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Host-Pathogen Interactions (genetics), Male, Mice, Mice, Knockout, Phenotype, Quantitative Trait Loci, SARS Virus (physiology), Severe Acute Respiratory Syndrome (diagnosis), Severe Acute Respiratory Syndrome (genetics), Severe Acute Respiratory Syndrome (virology), Viral Load.
- MESH :
- diagnosis : Severe Acute Respiratory Syndrome.
- genetics : Host-Pathogen Interactions, Severe Acute Respiratory Syndrome.
- physiology : SARS Virus.
- virology : Severe Acute Respiratory Syndrome.
- Alleles, Animals, Cell Line, Chromosome Mapping, Disease Models, Animal, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Male, Mice, Mice, Knockout, Phenotype, Quantitative Trait Loci, Viral Load.
Abstract
Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1–58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified
Url:
DOI: 10.1534/g3.117.041434
PubMed: 28592648
PubMed Central: 5473747
Affiliations:
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Le document en format XML
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Gralinski</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Epidemiology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Epidemiology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Morgan, Andrew P" sort="Morgan, Andrew P" uniqKey="Morgan A" first="Andrew P." last="Morgan">Andrew P. Morgan</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Genetics, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Totura, Allison L" sort="Totura, Allison L" uniqKey="Totura A" first="Allison L." last="Totura">Allison L. Totura</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Beall, Anne" sort="Beall, Anne" uniqKey="Beall A" first="Anne" last="Beall">Anne Beall</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Genetics, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Kocher, Jacob" sort="Kocher, Jacob" uniqKey="Kocher J" first="Jacob" last="Kocher">Jacob Kocher</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Epidemiology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Plante, Jessica" sort="Plante, Jessica" uniqKey="Plante J" first="Jessica" last="Plante">Jessica Plante</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Epidemiology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Harrison Shostak, D Corinne" sort="Harrison Shostak, D Corinne" uniqKey="Harrison Shostak D" first="D. Corinne" last="Harrison-Shostak">D. Corinne Harrison-Shostak</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Genetics, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Epidemiology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Genetics, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="aff4">Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T." last="Ferris">Martin T. Ferris</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Genetics, University of North Carolina, Chapel Hill</wicri:cityArea></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="aff1">Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Epidemiology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="aff4">Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill</wicri:cityArea></affiliation></author></analytic><series><title level="j">G3: Genes|Genomes|Genetics</title><idno type="eISSN">2160-1836</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term><term>Animals</term><term>Cell Line</term><term>Chromosome Mapping</term><term>Disease Models, Animal</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Genetic Variation</term><term>Genotype</term><term>Host-Pathogen Interactions (genetics)</term><term>Male</term><term>Mice</term><term>Mice, Knockout</term><term>Phenotype</term><term>Quantitative Trait Loci</term><term>SARS Virus (physiology)</term><term>Severe Acute Respiratory Syndrome (diagnosis)</term><term>Severe Acute Respiratory Syndrome (genetics)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Load</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allèles</term><term>Animaux</term><term>Cartographie chromosomique</term><term>Charge virale</term><term>Femelle</term><term>Génotype</term><term>Interactions hôte-pathogène (génétique)</term><term>Lignée cellulaire</term><term>Locus de caractère quantitatif</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Phénotype</term><term>Prédisposition génétique à une maladie</term><term>Souris</term><term>Souris knockout</term><term>Syndrome respiratoire aigu sévère (diagnostic)</term><term>Syndrome respiratoire aigu sévère (génétique)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Variation génétique</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Host-Pathogen Interactions</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interactions hôte-pathogène</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Animals</term><term>Cell Line</term><term>Chromosome Mapping</term><term>Disease Models, Animal</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Genetic Variation</term><term>Genotype</term><term>Male</term><term>Mice</term><term>Mice, Knockout</term><term>Phenotype</term><term>Quantitative Trait Loci</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Allèles</term><term>Animaux</term><term>Cartographie chromosomique</term><term>Charge virale</term><term>Femelle</term><term>Génotype</term><term>Lignée cellulaire</term><term>Locus de caractère quantitatif</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Phénotype</term><term>Prédisposition génétique à une maladie</term><term>Souris</term><term>Souris knockout</term><term>Variation génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1–58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified <italic>Ticam2</italic>, an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. <italic>Ticam2</italic><sup>−/−</sup> mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for <italic>Ticam2</italic> in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Adachi, O" uniqKey="Adachi O">O. Adachi</name></author><author><name sortKey="Kawai, T" uniqKey="Kawai T">T. Kawai</name></author><author><name sortKey="Takeda, K" uniqKey="Takeda K">K. Takeda</name></author><author><name sortKey="Matsumoto, M" uniqKey="Matsumoto M">M. Matsumoto</name></author><author><name sortKey="Tsutsui, H" uniqKey="Tsutsui H">H. 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Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name></author><author><name sortKey="Zhou, G" uniqKey="Zhou G">G. Zhou</name></author><author><name sortKey="Zhi, L" uniqKey="Zhi L">L. Zhi</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Zhai, Y" uniqKey="Zhai Y">Y. Zhai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, S Y" uniqKey="Zhang S">S. Y. Zhang</name></author><author><name sortKey="Jouanguy, E" uniqKey="Jouanguy E">E. Jouanguy</name></author><author><name sortKey="Ugolini, S" uniqKey="Ugolini S">S. Ugolini</name></author><author><name sortKey="Smahi, A" uniqKey="Smahi A">A. Smahi</name></author><author><name sortKey="Elain, G" uniqKey="Elain G">G. Elain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Legge, K" uniqKey="Legge K">K. Legge</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li></region></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name></region><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. 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="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Beall, Anne" sort="Beall, Anne" uniqKey="Beall A" first="Anne" last="Beall">Anne Beall</name><name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T." last="Ferris">Martin T. Ferris</name><name sortKey="Harrison Shostak, D Corinne" sort="Harrison Shostak, D Corinne" uniqKey="Harrison Shostak D" first="D. Corinne" last="Harrison-Shostak">D. Corinne Harrison-Shostak</name><name sortKey="Kocher, Jacob" sort="Kocher, Jacob" uniqKey="Kocher J" first="Jacob" last="Kocher">Jacob Kocher</name><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><name sortKey="Morgan, Andrew P" sort="Morgan, Andrew P" uniqKey="Morgan A" first="Andrew P." last="Morgan">Andrew P. Morgan</name><name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name><name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name><name sortKey="Plante, Jessica" sort="Plante, Jessica" uniqKey="Plante J" first="Jessica" last="Plante">Jessica Plante</name><name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name><name sortKey="Totura, Allison L" sort="Totura, Allison L" uniqKey="Totura A" first="Allison L." last="Totura">Allison L. Totura</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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