Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome
Identifieur interne : 001450 ( Ncbi/Merge ); précédent : 001449; suivant : 001451Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome
Auteurs : James V. Lawler ; Timothy P. Endy ; Lisa E. Hensley ; Aura Garrison ; Elizabeth A. Fritz ; May Lesar ; Ralph S. Baric ; David A. Kulesh ; David A. Norwood ; Leonard P. Wasieloski ; Melanie P. Ulrich ; Tom R. Slezak ; Elizabeth Vitalis ; John W. Huggins ; Peter B. Jahrling ; Jason ParagasSource :
- PLoS Medicine [ 1549-1277 ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Enfant d'âge préscolaire, Femelle, Humains, Indice de gravité médicale, Macaca fascicularis (virologie), Modèles animaux de maladie humaine, Muqueuse (virologie), Mâle, Production d'anticorps, Réplication virale, Syndrome, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (physiopathologie), Syndrome respiratoire aigu sévère (traitement médicamenteux), Vaccins, Virus du SRAS (pathogénicité), Virus du SRAS (physiologie).
- MESH :
- immunologie : Syndrome respiratoire aigu sévère.
- pathogénicité : Virus du SRAS.
- physiologie : Virus du SRAS.
- physiopathologie : Syndrome respiratoire aigu sévère.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- virologie : Macaca fascicularis, Muqueuse.
- Animaux, Enfant d'âge préscolaire, Femelle, Humains, Indice de gravité médicale, Modèles animaux de maladie humaine, Mâle, Production d'anticorps, Réplication virale, Syndrome, Syndrome respiratoire aigu sévère, Vaccins.
English descriptors
- KwdEn :
- Animals, Antibody Formation, Child, Preschool, Disease Models, Animal, Female, Humans, Macaca fascicularis (virology), Male, Mucous Membrane (virology), SARS Virus (pathogenicity), SARS Virus (physiology), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (physiopathology), Severe Acute Respiratory Syndrome (prevention & control), Severity of Illness Index, Syndrome, Vaccines, Virus Replication.
- MESH :
- chemical : Vaccines.
- drug therapy : Severe Acute Respiratory Syndrome.
- immunology : Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- physiology : SARS Virus.
- physiopathology : Severe Acute Respiratory Syndrome.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Macaca fascicularis, Mucous Membrane.
- Animals, Antibody Formation, Child, Preschool, Disease Models, Animal, Female, Humans, Male, Severity of Illness Index, Syndrome, Virus Replication.
Abstract
The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.
In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.
SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.
Url:
DOI: 10.1371/journal.pmed.0030149
PubMed: 16605302
PubMed Central: 1435788
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PMC:1435788Le document en format XML
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<term>Antibody Formation</term>
<term>Child, Preschool</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>Macaca fascicularis (virology)</term>
<term>Male</term>
<term>Mucous Membrane (virology)</term>
<term>SARS Virus (pathogenicity)</term>
<term>SARS Virus (physiology)</term>
<term>Severe Acute Respiratory Syndrome (drug therapy)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (physiopathology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
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<term>Indice de gravité médicale</term>
<term>Macaca fascicularis (virologie)</term>
<term>Modèles animaux de maladie humaine</term>
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<term>Réplication virale</term>
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<term>Syndrome respiratoire aigu sévère (immunologie)</term>
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<term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term>
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<term>Virus du SRAS (physiologie)</term>
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<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
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<front><div type="abstract" xml:lang="en"><sec id="st1"><title>Background</title>
<p>The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.</p>
</sec>
<sec id="st2"><title>Methods and Findings</title>
<p>In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.</p>
</sec>
<sec id="st3"><title>Conclusions</title>
<p>SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.</p>
</sec>
</div>
</front>
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<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="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kulesh, David A" sort="Kulesh, David A" uniqKey="Kulesh D" first="David A" last="Kulesh">David A. Kulesh</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Norwood, David A" sort="Norwood, David A" uniqKey="Norwood D" first="David A" last="Norwood">David A. Norwood</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wasieloski, Leonard P" sort="Wasieloski, Leonard P" uniqKey="Wasieloski L" first="Leonard P" last="Wasieloski">Leonard P. Wasieloski</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ulrich, Melanie P" sort="Ulrich, Melanie P" uniqKey="Ulrich M" first="Melanie P" last="Ulrich">Melanie P. Ulrich</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slezak, Tom R" sort="Slezak, Tom R" uniqKey="Slezak T" first="Tom R" last="Slezak">Tom R. Slezak</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vitalis, Elizabeth" sort="Vitalis, Elizabeth" uniqKey="Vitalis E" first="Elizabeth" last="Vitalis">Elizabeth Vitalis</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huggins, John W" sort="Huggins, John W" uniqKey="Huggins J" first="John W" last="Huggins">John W. Huggins</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name>
<affiliation><nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paragas, Jason" sort="Paragas, Jason" uniqKey="Paragas J" first="Jason" last="Paragas">Jason Paragas</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">16605302</idno>
<idno type="pmc">1435788</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1435788</idno>
<idno type="RBID">PMC:1435788</idno>
<idno type="doi">10.1371/journal.pmed.0030149</idno>
<date when="2006">2006</date>
<idno type="wicri:Area/Pmc/Corpus">001336</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001336</idno>
<idno type="wicri:Area/Pmc/Curation">001336</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001336</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001143</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001143</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome</title>
<author><name sortKey="Lawler, James V" sort="Lawler, James V" uniqKey="Lawler J" first="James V" last="Lawler">James V. Lawler</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Endy, Timothy P" sort="Endy, Timothy P" uniqKey="Endy T" first="Timothy P" last="Endy">Timothy P. Endy</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E" last="Hensley">Lisa E. Hensley</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Garrison, Aura" sort="Garrison, Aura" uniqKey="Garrison A" first="Aura" last="Garrison">Aura Garrison</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fritz, Elizabeth A" sort="Fritz, Elizabeth A" uniqKey="Fritz E" first="Elizabeth A" last="Fritz">Elizabeth A. Fritz</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lesar, May" sort="Lesar, May" uniqKey="Lesar M" first="May" last="Lesar">May Lesar</name>
<affiliation><nlm:aff id="aff3"></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="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kulesh, David A" sort="Kulesh, David A" uniqKey="Kulesh D" first="David A" last="Kulesh">David A. Kulesh</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Norwood, David A" sort="Norwood, David A" uniqKey="Norwood D" first="David A" last="Norwood">David A. Norwood</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wasieloski, Leonard P" sort="Wasieloski, Leonard P" uniqKey="Wasieloski L" first="Leonard P" last="Wasieloski">Leonard P. Wasieloski</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ulrich, Melanie P" sort="Ulrich, Melanie P" uniqKey="Ulrich M" first="Melanie P" last="Ulrich">Melanie P. Ulrich</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slezak, Tom R" sort="Slezak, Tom R" uniqKey="Slezak T" first="Tom R" last="Slezak">Tom R. Slezak</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vitalis, Elizabeth" sort="Vitalis, Elizabeth" uniqKey="Vitalis E" first="Elizabeth" last="Vitalis">Elizabeth Vitalis</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huggins, John W" sort="Huggins, John W" uniqKey="Huggins J" first="John W" last="Huggins">John W. Huggins</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name>
<affiliation><nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Paragas, Jason" sort="Paragas, Jason" uniqKey="Paragas J" first="Jason" last="Paragas">Jason Paragas</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Medicine</title>
<idno type="ISSN">1549-1277</idno>
<idno type="eISSN">1549-1676</idno>
<imprint><date when="2006">2006</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="st1"><title>Background</title>
<p>The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.</p>
</sec>
<sec id="st2"><title>Methods and Findings</title>
<p>In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.</p>
</sec>
<sec id="st3"><title>Conclusions</title>
<p>SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.</p>
</sec>
</div>
</front>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cynomolgus macaque as an animal model for severe acute respiratory syndrome.</title>
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<affiliation wicri:level="2"><nlm:affiliation>Infectious Diseases Department, National Naval Medical Center, Bethesda, Maryland, United States of America.</nlm:affiliation>
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</affiliation>
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<author><name sortKey="Endy, Timothy P" sort="Endy, Timothy P" uniqKey="Endy T" first="Timothy P" last="Endy">Timothy P. Endy</name>
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<author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E" last="Hensley">Lisa E. Hensley</name>
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<author><name sortKey="Garrison, Aura" sort="Garrison, Aura" uniqKey="Garrison A" first="Aura" last="Garrison">Aura Garrison</name>
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<author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name>
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<author><name sortKey="Kulesh, David A" sort="Kulesh, David A" uniqKey="Kulesh D" first="David A" last="Kulesh">David A. Kulesh</name>
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<author><name sortKey="Vitalis, Elizabeth" sort="Vitalis, Elizabeth" uniqKey="Vitalis E" first="Elizabeth" last="Vitalis">Elizabeth Vitalis</name>
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<front><div type="abstract" xml:lang="en">The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.</div>
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