Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice
Identifieur interne : 003B20 ( Main/Exploration ); précédent : 003B19; suivant : 003B21Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice
Auteurs : Barry Rockx [États-Unis] ; Timothy Sheahan [États-Unis] ; Eric Donaldson [États-Unis] ; Jack Harkema [États-Unis] ; Amy Sims [États-Unis] ; Mark Heise [États-Unis] ; Raymond Pickles [États-Unis] ; Mark Cameron [Canada] ; David Kelvin [Canada] ; Ralph Baric [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- Amorces ADN, Animaux, Cellules Vero, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (génétique), Mutation, Phylogénie, Poumon (anatomopathologie), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Réplication virale (génétique), Similitude de séquences d'acides aminés, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (anatomopathologie), Séquence d'acides aminés, Séquence nucléotidique, Virus du SRAS (), Virus du SRAS (isolement et purification), Virus du SRAS (pathogénicité), Zoonoses.
- MESH :
- anatomopathologie : Poumon, Syndrome respiratoire aigu sévère.
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Réplication virale.
- isolement et purification : Virus du SRAS.
- pathogénicité : Virus du SRAS.
- Pascal (Inist)
- Amorces ADN, Animaux, Cellules Vero, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Homme, Coronavirus, Mutation, Phylogénie, Protéines de l'enveloppe virale, Similitude de séquences d'acides aminés, Souris, Aigu, Isolat, Mort, Animal, Souris de lignée BALB C, Séquence d'acides aminés, Séquence nucléotidique, Virologie, Virus du SRAS, Zoonoses.
- Wicri :
English descriptors
- KwdEn :
- Acute, Amino Acid Sequence, Animal, Animals, Base Sequence, Chlorocebus aethiops, Coronavirus, DNA Primers, Death, Female, Human, Isolate, Lung (pathology), Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mouse, Mutation, Phylogeny, SARS Virus (chemistry), SARS Virus (isolation & purification), SARS Virus (pathogenicity), Sequence Homology, Amino Acid, Severe Acute Respiratory Syndrome (pathology), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Virology, Virus Replication (genetics), Zoonoses.
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical : DNA Primers, Spike Glycoprotein, Coronavirus.
- chemistry : SARS Virus.
- genetics : Virus Replication.
- isolation & purification : SARS Virus.
- pathogenicity : SARS Virus.
- pathology : Lung, Severe Acute Respiratory Syndrome.
- Amino Acid Sequence, Animals, Base Sequence, Chlorocebus aethiops, Female, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Phylogeny, Sequence Homology, Amino Acid, Vero Cells, Zoonoses.
Abstract
The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.
Url:
Affiliations:
- Canada, États-Unis
- Caroline du Nord, Michigan, Ontario
- Chapel Hill (Caroline du Nord), East Lansing, Toronto
- Université d'État du Michigan, Université de Caroline du Nord à Chapel Hill, Université de Toronto
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 000334
- to stream PascalFrancis, to step Curation: 000655
- to stream PascalFrancis, to step Checkpoint: 000328
- to stream Main, to step Merge: 003C75
- to stream Pmc, to step Corpus: 000717
- to stream Pmc, to step Curation: 000717
- to stream Pmc, to step Checkpoint: 000E87
- to stream PubMed, to step Corpus: 001E12
- to stream PubMed, to step Curation: 001E12
- to stream PubMed, to step Checkpoint: 001C74
- to stream Ncbi, to step Merge: 001966
- to stream Ncbi, to step Curation: 001966
- to stream Ncbi, to step Checkpoint: 001966
- to stream Main, to step Merge: 003698
- to stream Main, to step Curation: 003B20
Le document en format XML
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mice</title><author><name sortKey="Rockx, Barry" sort="Rockx, Barry" uniqKey="Rockx B" first="Barry" last="Rockx">Barry Rockx</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Sheahan, Timothy" sort="Sheahan, Timothy" uniqKey="Sheahan T" first="Timothy" last="Sheahan">Timothy Sheahan</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Harkema, Jack" sort="Harkema, Jack" uniqKey="Harkema J" first="Jack" last="Harkema">Jack Harkema</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University</s1><s2>East Lansing, Michigan</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region><settlement type="city">East Lansing</settlement></placeName><orgName type="university">Université d'État du Michigan</orgName></affiliation></author><author><name sortKey="Sims, Amy" sort="Sims, Amy" uniqKey="Sims A" first="Amy" last="Sims">Amy Sims</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Pickles, Raymond" sort="Pickles, Raymond" uniqKey="Pickles R" first="Raymond" last="Pickles">Raymond Pickles</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Cameron, Mark" sort="Cameron, Mark" uniqKey="Cameron M" first="Mark" last="Cameron">Mark Cameron</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>University Health Network, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Kelvin, David" sort="Kelvin, David" uniqKey="Kelvin D" first="David" last="Kelvin">David Kelvin</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>University Health Network, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute</term><term>Amino Acid Sequence</term><term>Animal</term><term>Animals</term><term>Base Sequence</term><term>Chlorocebus aethiops</term><term>Coronavirus</term><term>DNA Primers</term><term>Death</term><term>Female</term><term>Human</term><term>Isolate</term><term>Lung (pathology)</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (genetics)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Mouse</term><term>Mutation</term><term>Phylogeny</term><term>SARS Virus (chemistry)</term><term>SARS Virus (isolation & purification)</term><term>SARS Virus (pathogenicity)</term><term>Sequence Homology, Amino Acid</term><term>Severe Acute Respiratory Syndrome (pathology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (genetics)</term><term>Virology</term><term>Virus Replication (genetics)</term><term>Zoonoses</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amorces ADN</term><term>Animaux</term><term>Cellules Vero</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (génétique)</term><term>Mutation</term><term>Phylogénie</term><term>Poumon (anatomopathologie)</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Réplication virale (génétique)</term><term>Similitude de séquences d'acides aminés</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère (anatomopathologie)</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Virus du SRAS ()</term><term>Virus du SRAS (isolement et purification)</term><term>Virus du SRAS (pathogénicité)</term><term>Zoonoses</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>DNA Primers</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Réplication virale</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Base Sequence</term><term>Chlorocebus aethiops</term><term>Female</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Phylogeny</term><term>Sequence Homology, Amino Acid</term><term>Vero Cells</term><term>Zoonoses</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Amorces ADN</term><term>Animaux</term><term>Cellules Vero</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Homme</term><term>Coronavirus</term><term>Mutation</term><term>Phylogénie</term><term>Protéines de l'enveloppe virale</term><term>Similitude de séquences d'acides aminés</term><term>Souris</term><term>Aigu</term><term>Isolat</term><term>Mort</term><term>Animal</term><term>Souris de lignée BALB C</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Virologie</term><term>Virus du SRAS</term><term>Zoonoses</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term><term>Mort</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Michigan</li><li>Ontario</li></region><settlement><li>Chapel Hill (Caroline du Nord)</li><li>East Lansing</li><li>Toronto</li></settlement><orgName><li>Université d'État du Michigan</li><li>Université de Caroline du Nord à Chapel Hill</li><li>Université de Toronto</li></orgName></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Rockx, Barry" sort="Rockx, Barry" uniqKey="Rockx B" first="Barry" last="Rockx">Barry Rockx</name></region><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name><name sortKey="Harkema, Jack" sort="Harkema, Jack" uniqKey="Harkema J" first="Jack" last="Harkema">Jack Harkema</name><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><name sortKey="Pickles, Raymond" sort="Pickles, Raymond" uniqKey="Pickles R" first="Raymond" last="Pickles">Raymond Pickles</name><name sortKey="Pickles, Raymond" sort="Pickles, Raymond" uniqKey="Pickles R" first="Raymond" last="Pickles">Raymond Pickles</name><name sortKey="Sheahan, Timothy" sort="Sheahan, Timothy" uniqKey="Sheahan T" first="Timothy" last="Sheahan">Timothy Sheahan</name><name sortKey="Sims, Amy" sort="Sims, Amy" uniqKey="Sims A" first="Amy" last="Sims">Amy Sims</name></country><country name="Canada"><region name="Ontario"><name sortKey="Cameron, Mark" sort="Cameron, Mark" uniqKey="Cameron M" first="Mark" last="Cameron">Mark Cameron</name></region><name sortKey="Kelvin, David" sort="Kelvin, David" uniqKey="Kelvin D" first="David" last="Kelvin">David Kelvin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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