A mouse model for MERS coronavirus-induced acute respiratory distress syndrome
Identifieur interne : 001403 ( Main/Exploration ); précédent : 001402; suivant : 001404A mouse model for MERS coronavirus-induced acute respiratory distress syndrome
Auteurs : Adam S. Cockrell ; Boyd L. Yount ; Trevor Scobey ; Kara Jensen ; Madeline Douglas ; Anne Beall ; Xian-Chun Tang [États-Unis] ; Wayne A. Marasco [États-Unis] ; Mark T. Heise ; Ralph S. BaricSource :
- Nature Microbiology [ 2058-5276 ] ; 2016.
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.
The online version of this article (doi:10.1038/nmicrobiol.2016.226) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/nmicrobiol.2016.226
PubMed: 27892925
PubMed Central: 5578707
Affiliations:
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Cockrell</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author><author><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L." last="Yount">Boyd L. Yount</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author><author><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author><author><name sortKey="Jensen, Kara" sort="Jensen, Kara" uniqKey="Jensen K" first="Kara" last="Jensen">Kara Jensen</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author><author><name sortKey="Douglas, Madeline" sort="Douglas, Madeline" uniqKey="Douglas M" first="Madeline" last="Douglas">Madeline Douglas</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author><author><name sortKey="Beall, Anne" sort="Beall, Anne" uniqKey="Beall A" first="Anne" last="Beall">Anne Beall</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author><author><name sortKey="Tang, Xian Chun" sort="Tang, Xian Chun" uniqKey="Tang X" first="Xian-Chun" last="Tang">Xian-Chun Tang</name><affiliation wicri:level="2"><nlm:aff id="Aff2">Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02215 USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution>Department of Medicine,</institution><institution>Harvard Medical School, Boston, Massachusetts,</institution></institution-wrap>02115 USA</nlm:aff></affiliation></author><author><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A." last="Marasco">Wayne A. Marasco</name><affiliation wicri:level="2"><nlm:aff id="Aff2">Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02215 USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution>Department of Medicine,</institution><institution>Harvard Medical School, Boston, Massachusetts,</institution></institution-wrap>02115 USA</nlm:aff></affiliation></author><author><name sortKey="Heise, Mark T" sort="Heise, Mark T" uniqKey="Heise M" first="Mark T." last="Heise">Mark T. Heise</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Departments of Microbiology and Immunology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Departments of Genetics,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></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><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Epidemiology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Departments of Microbiology and Immunology,</institution><institution>University of North Carolina-Chapel Hill, Chapel Hill, North Carolina,</institution></institution-wrap>27599 USA</nlm:aff></affiliation></author></analytic><series><title level="j">Nature Microbiology</title><idno type="eISSN">2058-5276</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Coronavirus Infections (complications)</term><term>Dipeptidyl Peptidase 4 (genetics)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Disease Models, Animal</term><term>Gene Editing</term><term>Mice</term><term>Middle East Respiratory Syndrome Coronavirus (growth & development)</term><term>Mutant Proteins (genetics)</term><term>Mutant Proteins (metabolism)</term><term>Organisms, Genetically Modified</term><term>Receptors, Virus (genetics)</term><term>Receptors, Virus (metabolism)</term><term>Recombination, Genetic</term><term>Respiratory Distress Syndrome, Adult (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement)</term><term>Dipeptidyl peptidase 4 (génétique)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Infections à coronavirus ()</term><term>Modèles animaux de maladie humaine</term><term>Organismes génétiquement modifiés</term><term>Protéines mutantes (génétique)</term><term>Protéines mutantes (métabolisme)</term><term>Recombinaison génétique</term><term>Récepteurs viraux (génétique)</term><term>Récepteurs viraux (métabolisme)</term><term>Souris</term><term>Syndrome de détresse respiratoire de l'adulte (anatomopathologie)</term><term>Édition de gène</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Mutant Proteins</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Syndrome de détresse respiratoire de l'adulte</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Dipeptidyl peptidase 4</term><term>Protéines mutantes</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Mutant Proteins</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</term><term>Protéines mutantes</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Respiratory Distress Syndrome, Adult</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Gene Editing</term><term>Mice</term><term>Organisms, Genetically Modified</term><term>Recombination, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Infections à coronavirus</term><term>Modèles animaux de maladie humaine</term><term>Organismes génétiquement modifiés</term><term>Recombinaison génétique</term><term>Souris</term><term>Édition de gène</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nmicrobiol.2016.226) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chan, Jf W" uniqKey="Chan J">JF-W Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Rf" uniqKey="Johnson R">RF Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Rf" uniqKey="Johnson R">RF Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cockrell, As" uniqKey="Cockrell A">AS Cockrell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, Cm" uniqKey="Coleman C">CM Coleman</name></author><author><name sortKey="Matthews, Kl" uniqKey="Matthews K">KL Matthews</name></author><author><name sortKey="Goicochea, L" uniqKey="Goicochea L">L Goicochea</name></author><author><name sortKey="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ohnuma, K" uniqKey="Ohnuma K">K Ohnuma</name></author><author><name sortKey="Dang, Nh" uniqKey="Dang N">NH Dang</name></author><author><name sortKey="Morimoto, C" uniqKey="Morimoto C">C Morimoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, K" uniqKey="Li K">K Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambeir, Am" uniqKey="Lambeir A">AM Lambeir</name></author><author><name sortKey="Durinx, C" uniqKey="Durinx C">C Durinx</name></author><author><name sortKey="Scharpe, S" uniqKey="Scharpe S">S Scharpe</name></author><author><name sortKey="De Meester, I" uniqKey="De Meester I">I de Meester</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author><author><name sortKey="Gralinski, Le" uniqKey="Gralinski L">LE Gralinski</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author><author><name sortKey="Ferris, Mt" uniqKey="Ferris M">MT Ferris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Dl" uniqKey="Ng D">DL Ng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Korteweg, C" uniqKey="Korteweg C">C Korteweg</name></author><author><name sortKey="Gu, J" uniqKey="Gu J">J Gu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, W F" uniqKey="Ng W">W-F Ng</name></author><author><name sortKey="To, K F" uniqKey="To K">K-F To</name></author><author><name sortKey="Lam, Ww" uniqKey="Lam W">WW Lam</name></author><author><name sortKey="Ng, T K" uniqKey="Ng T">T-K Ng</name></author><author><name sortKey="Lee, K C" uniqKey="Lee K">K-C Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sanders, Cj" uniqKey="Sanders C">CJ Sanders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascal, Ke" uniqKey="Pascal K">KE Pascal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frieman, M" uniqKey="Frieman M">M Frieman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thornbrough, Jm" uniqKey="Thornbrough J">JM Thornbrough</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML Dediego</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laksitorini, M" uniqKey="Laksitorini M">M Laksitorini</name></author><author><name sortKey="Prasasty, Vd" uniqKey="Prasasty V">VD Prasasty</name></author><author><name sortKey="Kiptoo, Pk" uniqKey="Kiptoo P">PK Kiptoo</name></author><author><name sortKey="Siahaan, Tj" uniqKey="Siahaan T">TJ Siahaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccray, Pb" uniqKey="Mccray P">PB McCray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lamers, Mm" uniqKey="Lamers M">MM Lamers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scobey, T" uniqKey="Scobey T">T Scobey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mali, P" uniqKey="Mali P">P Mali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ayala, Je" uniqKey="Ayala J">JE Ayala</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li></region></list><tree><noCountry><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="Cockrell, Adam S" sort="Cockrell, Adam S" uniqKey="Cockrell A" first="Adam S." last="Cockrell">Adam S. Cockrell</name><name sortKey="Douglas, Madeline" sort="Douglas, Madeline" uniqKey="Douglas M" first="Madeline" last="Douglas">Madeline Douglas</name><name sortKey="Heise, Mark T" sort="Heise, Mark T" uniqKey="Heise M" first="Mark T." last="Heise">Mark T. Heise</name><name sortKey="Jensen, Kara" sort="Jensen, Kara" uniqKey="Jensen K" first="Kara" last="Jensen">Kara Jensen</name><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L." last="Yount">Boyd L. Yount</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Tang, Xian Chun" sort="Tang, Xian Chun" uniqKey="Tang X" first="Xian-Chun" last="Tang">Xian-Chun Tang</name></region><name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A." last="Marasco">Wayne A. Marasco</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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