Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome
Identifieur interne : 001336 ( Pmc/Curation ); précédent : 001335; suivant : 001337Cynomolgus 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.
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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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. 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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></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><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Stohr, K" uniqKey="Stohr K">K Stohr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan Yeung, M" uniqKey="Chan Yeung M">M Chan-Yeung</name></author><author><name sortKey="Xu, Rh" uniqKey="Xu R">RH 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Med</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Med</journal-id><journal-id journal-id-type="publisher-id">pmed</journal-id><journal-id journal-id-type="pmc">plosmed</journal-id><journal-title-group><journal-title>PLoS Medicine</journal-title></journal-title-group><issn pub-type="ppub">1549-1277</issn><issn pub-type="epub">1549-1676</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">16605302</article-id><article-id pub-id-type="pmc">1435788</article-id><article-id pub-id-type="doi">10.1371/journal.pmed.0030149</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Infectious Diseases</subject><subject>Microbiology</subject><subject>Virology</subject><subject>Medical Imaging</subject></subj-group><subj-group subj-group-type="System Taxonomy"><subject>Infectious Diseases</subject></subj-group></article-categories><title-group><article-title>Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome</article-title><alt-title alt-title-type="running-head">SARS-CoV Infection of NHPs</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lawler</surname><given-names>James V</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="n2">¤a</xref></contrib><contrib contrib-type="author"><name><surname>Endy</surname><given-names>Timothy P</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="n3">¤b</xref></contrib><contrib contrib-type="author"><name><surname>Hensley</surname><given-names>Lisa E</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Garrison</surname><given-names>Aura</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fritz</surname><given-names>Elizabeth A</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lesar</surname><given-names>May</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Baric</surname><given-names>Ralph S</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kulesh</surname><given-names>David A</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Norwood</surname><given-names>David A</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wasieloski</surname><given-names>Leonard P</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ulrich</surname><given-names>Melanie P</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Slezak</surname><given-names>Tom R</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vitalis</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huggins</surname><given-names>John W</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jahrling</surname><given-names>Peter B</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="author-notes" rid="n4">¤c</xref></contrib><contrib contrib-type="author"><name><surname>Paragas</surname><given-names>Jason</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1"><bold>1</bold>Infectious Diseases Department, National Naval Medical Center (NNMC), Bethesda, Maryland, United States of America</aff><aff id="aff2"><bold>2</bold>Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, United States of America</aff><aff id="aff3"><bold>3</bold>Radiology Division, National Naval Medical Center (NNMC); Bethesda, Maryland, United States of America</aff><aff id="aff4"><bold>4</bold>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America</aff><aff id="aff5"><bold>5</bold>Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, United States of America</aff><aff id="aff6"><bold>6</bold>Lawrence Livermore National Laboratory, Livermore, California, United States of America</aff><aff id="aff7"><bold>7</bold>Headquarters Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, United States of America</aff><contrib-group><contrib contrib-type="editor"><name><surname>Peiris</surname><given-names>Joseph S. M.</given-names></name><role>Academic Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><institution>The University of Hong Kong</institution><country>China</country></aff><author-notes><corresp id="cor1">* To whom correspondence should be addressed. E-mail:
<email>jason.paragas@det.amedd.army.mil</email></corresp><fn id="n2" fn-type="current-aff"><p>¤a Current address: Division of Medicine, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, United States of America</p></fn><fn id="n3" fn-type="current-aff"><p>¤b Current address: Communicable Diseases and Immunology Division, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America</p></fn><fn id="n4" fn-type="current-aff"><p>¤c Current address: National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Maryland, United States of America</p></fn><fn id="n5" fn-type="COI-statement"><p><bold>Competing Interests:</bold> The authors have declared that no competing interests exist.
</p></fn></author-notes><pub-date pub-type="ppub"><month>5</month><year>2006</year></pub-date><pub-date pub-type="epub"><day>18</day><month>4</month><year>2006</year></pub-date><volume>3</volume><issue>5</issue><elocation-id>e149</elocation-id><history><date date-type="received"><day>5</day><month>7</month><year>2005</year></date><date date-type="accepted"><day>10</day><month>1</month><year>2006</year></date></history><permissions><copyright-statement>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</copyright-statement><copyright-year>2006</copyright-year><license xlink:href="https://creativecommons.org/publicdomain/zero/1.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</license-p></license></permissions><related-article id="d35e336" related-article-type="companion" ext-link-type="doi" xlink:href="10.1371/journal.pmed.0030194" xlink:title="perspective" vol="3" page="e194"><article-title>Nonhuman Primate Models for SARS</article-title></related-article><related-article id="d35e341" related-article-type="companion" ext-link-type="doi" xlink:href="10.1371/journal.pmed.0030222" xlink:title="synopsis" vol="3" page="e222"><article-title>A Macaque Model of SARS</article-title></related-article><abstract><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></abstract><abstract abstract-type="toc"><p>Jason Paragas and colleagues report the first findings of measurable clinical disease in nonhuman primates infected with the virus that causes SARS, SARS-CoV.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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