SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis
Identifieur interne : 001249 ( Pmc/Checkpoint ); précédent : 001248; suivant : 001250SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis
Auteurs : Jianjun Liu ; Siew Lan Lim ; Yijun Ruan ; Ai Ee Ling ; Lisa F. P. Ng ; Christian Drosten ; Edison T. Liu ; Lawrence W. Stanton ; Martin L. HibberdSource :
- PLoS Medicine [ 1549-1277 ] ; 2005.
Abstract
Epidemiological investigations of infectious disease are mainly dependent on indirect contact information and only occasionally assisted by characterization of pathogen sequence variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive. We present here a novel application of mass spectrometry (MS)–based technology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak in Singapore.
The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be 95% with 75 copies of viral RNA per reaction, which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from the different stages of the Singapore outbreak identified nine sequence variations that could define the molecular relationship between them and pointed to a new, previously unidentified, primary route of introduction of SARS-CoV into the Singapore population. Our direct determination of viral sequence variation from a clinical sample also clarified an unresolved epidemiological link regarding the acquisition of SARS in a German patient. We were also able to detect heterogeneous viral sequences in primary lung tissues, suggesting a possible coevolution of quasispecies of virus within a single host.
This study has further demonstrated the importance of improving clinical and epidemiological studies of pathogen transmission through the use of genetic analysis and has revealed the MS-based analysis to be a sensitive and accurate method for characterizing SARS-CoV genetic variations in clinical samples. We suggest that this approach should be used routinely during outbreaks of a wide variety of agents, in order to allow the most effective control.
Url:
DOI: 10.1371/journal.pmed.0020043
PubMed: 15736999
PubMed Central: 549591
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis</title><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lim, Siew Lan" sort="Lim, Siew Lan" uniqKey="Lim S" first="Siew Lan" last="Lim">Siew Lan Lim</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ruan, Yijun" sort="Ruan, Yijun" uniqKey="Ruan Y" first="Yijun" last="Ruan">Yijun Ruan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ling, Ai Ee" sort="Ling, Ai Ee" uniqKey="Ling A" first="Ai Ee" last="Ling">Ai Ee Ling</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Ng, Lisa F P" sort="Ng, Lisa F P" uniqKey="Ng L" first="Lisa F. P" last="Ng">Lisa F. P. Ng</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Liu, Edison T" sort="Liu, Edison T" uniqKey="Liu E" first="Edison T" last="Liu">Edison T. Liu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Stanton, Lawrence W" sort="Stanton, Lawrence W" uniqKey="Stanton L" first="Lawrence W" last="Stanton">Lawrence W. Stanton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Hibberd, Martin L" sort="Hibberd, Martin L" uniqKey="Hibberd M" first="Martin L" last="Hibberd">Martin L. Hibberd</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15736999</idno><idno type="pmc">549591</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC549591</idno><idno type="RBID">PMC:549591</idno><idno type="doi">10.1371/journal.pmed.0020043</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">001335</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001335</idno><idno type="wicri:Area/Pmc/Curation">001335</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001335</idno><idno type="wicri:Area/Pmc/Checkpoint">001249</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001249</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis</title><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lim, Siew Lan" sort="Lim, Siew Lan" uniqKey="Lim S" first="Siew Lan" last="Lim">Siew Lan Lim</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ruan, Yijun" sort="Ruan, Yijun" uniqKey="Ruan Y" first="Yijun" last="Ruan">Yijun Ruan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ling, Ai Ee" sort="Ling, Ai Ee" uniqKey="Ling A" first="Ai Ee" last="Ling">Ai Ee Ling</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Ng, Lisa F P" sort="Ng, Lisa F P" uniqKey="Ng L" first="Lisa F. P" last="Ng">Lisa F. P. Ng</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Liu, Edison T" sort="Liu, Edison T" uniqKey="Liu E" first="Edison T" last="Liu">Edison T. Liu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Stanton, Lawrence W" sort="Stanton, Lawrence W" uniqKey="Stanton L" first="Lawrence W" last="Stanton">Lawrence W. Stanton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Hibberd, Martin L" sort="Hibberd, Martin L" uniqKey="Hibberd M" first="Martin L" last="Hibberd">Martin L. Hibberd</name><affiliation><nlm:aff id="aff1"></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="2005">2005</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>Epidemiological investigations of infectious disease are mainly dependent on indirect contact information and only occasionally assisted by characterization of pathogen sequence variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive. We present here a novel application of mass spectrometry (MS)–based technology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak in Singapore.</p></sec><sec id="st2"><title>Methods and Findings</title><p>The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be 95% with 75 copies of viral RNA per reaction, which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from the different stages of the Singapore outbreak identified nine sequence variations that could define the molecular relationship between them and pointed to a new, previously unidentified, primary route of introduction of SARS-CoV into the Singapore population. Our direct determination of viral sequence variation from a clinical sample also clarified an unresolved epidemiological link regarding the acquisition of SARS in a German patient. We were also able to detect heterogeneous viral sequences in primary lung tissues, suggesting a possible coevolution of quasispecies of virus within a single host.</p></sec><sec id="st3"><title>Conclusion</title><p>This study has further demonstrated the importance of improving clinical and epidemiological studies of pathogen transmission through the use of genetic analysis and has revealed the MS-based analysis to be a sensitive and accurate method for characterizing SARS-CoV genetic variations in clinical samples. We suggest that this approach should be used routinely during outbreaks of a wide variety of agents, in order to allow the most effective control.</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="Kwok, Yy" uniqKey="Kwok Y">YY Kwok</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Stohr, K" uniqKey="Stohr K">K Stöhr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marra, Ma" uniqKey="Marra M">MA Marra</name></author><author><name sortKey="Jones, Sj" uniqKey="Jones S">SJ Jones</name></author><author><name sortKey="Astell, Cr" uniqKey="Astell C">CR Astell</name></author><author><name sortKey="Holt, Ra" uniqKey="Holt R">RA Holt</name></author><author><name sortKey="Brooks Wilson, A" uniqKey="Brooks Wilson A">A 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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">15736999</article-id><article-id pub-id-type="pmc">549591</article-id><article-id pub-id-type="doi">10.1371/journal.pmed.0020043</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Biotechnology</subject><subject>Genetics/Genomics/Gene Therapy</subject><subject>Infectious Diseases</subject><subject>Microbiology</subject><subject>Epidemiology/Public Health</subject><subject>Health Policy</subject><subject>Pathology</subject><subject>Respiratory Medicine</subject></subj-group><subj-group subj-group-type="System Taxonomy"><subject>Infectious Diseases</subject><subject>Genetics</subject><subject>Global health</subject><subject>Screening</subject></subj-group></article-categories><title-group><article-title>SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis</article-title><alt-title alt-title-type="running-head">SRAS Transmission in Singapore</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Jianjun</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="n3">*</xref></contrib><contrib contrib-type="author"><name><surname>Lim</surname><given-names>Siew Lan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ruan</surname><given-names>Yijun</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ling</surname><given-names>Ai Ee</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ng</surname><given-names>Lisa F. P</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Drosten</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Edison T</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stanton</surname><given-names>Lawrence W</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hibberd</surname><given-names>Martin L</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff1"><bold>1</bold><institution>Genome Institute of Singapore</institution><addr-line>Singapore</addr-line><country>Singapore</country></aff><aff id="aff2"><bold>2</bold><institution>Department of Pathology, Singapore General Hospital</institution><country>Singapore</country></aff><aff id="aff3"><bold>3</bold><institution>Bernhard Nocht Institute for Tropical Medicine, National Reference Center for Tropical Infectious Diseases</institution><addr-line>Hamburg</addr-line><country>Germany</country></aff><contrib-group><contrib contrib-type="editor"><name><surname>Sibbald</surname><given-names>William</given-names></name><role>Academic Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><institution>Sunnybrook and Women's College Health Sciences Centre</institution><country>Canada</country></aff><author-notes><fn id="n1" fn-type="COI-statement"><p><bold>Competing Interests:</bold> The authors have declared that no competing interests exist.</p><p>ETL is a member of the Editorial Board of <italic>PLOS Medicine.</italic></p></fn><fn id="n2" fn-type="con"><p><bold>Author Contributions:</bold> JL, ETL, LWS, and MLH designed the study. JL, SLL, and CD analyzed the data. LFPN performed the experiments. YR coordinated sample acquiring and provided the genome sequence variation data for designing MS assays. AEL provided SARS-CoV samples from patients. JL, SLL, YR, AEL, LFPN, CD, ETL, LWS, and MLH contributed to writing the paper.</p></fn><corresp id="n3">*To whom correspondence should be addressed. E-mail: <email>liuj3@gis.a-star.edu.sg</email></corresp></author-notes><pub-date pub-type="ppub"><month>2</month><year>2005</year></pub-date><pub-date pub-type="epub"><day>22</day><month>2</month><year>2005</year></pub-date><volume>2</volume><issue>2</issue><elocation-id>e43</elocation-id><history><date date-type="received"><day>4</day><month>8</month><year>2004</year></date><date date-type="accepted"><day>17</day><month>12</month><year>2004</year></date></history><permissions><copyright-statement>Copyright: © 2005 Liu et al.</copyright-statement><copyright-year>2005</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><related-article id="d35e264" related-article-type="companion" ext-link-type="doi" xlink:href="10.1371/journal.pmed.0020052" xlink:title="synopsis" vol="2" page="e52"><article-title>Mass Spectometry-Based SARS Genotyping</article-title></related-article><abstract><sec id="st1"><title>Background</title><p>Epidemiological investigations of infectious disease are mainly dependent on indirect contact information and only occasionally assisted by characterization of pathogen sequence variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive. We present here a novel application of mass spectrometry (MS)–based technology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak in Singapore.</p></sec><sec id="st2"><title>Methods and Findings</title><p>The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be 95% with 75 copies of viral RNA per reaction, which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from the different stages of the Singapore outbreak identified nine sequence variations that could define the molecular relationship between them and pointed to a new, previously unidentified, primary route of introduction of SARS-CoV into the Singapore population. Our direct determination of viral sequence variation from a clinical sample also clarified an unresolved epidemiological link regarding the acquisition of SARS in a German patient. We were also able to detect heterogeneous viral sequences in primary lung tissues, suggesting a possible coevolution of quasispecies of virus within a single host.</p></sec><sec id="st3"><title>Conclusion</title><p>This study has further demonstrated the importance of improving clinical and epidemiological studies of pathogen transmission through the use of genetic analysis and has revealed the MS-based analysis to be a sensitive and accurate method for characterizing SARS-CoV genetic variations in clinical samples. We suggest that this approach should be used routinely during outbreaks of a wide variety of agents, in order to allow the most effective control.</p></sec></abstract><abstract abstract-type="toc"><p>Mass spectrometry-based sequence analysis provides a sensitive and accurate method to characterize genetic variation of the SARS coronavirus in clinical samples</p></abstract></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Hibberd, Martin L" sort="Hibberd, Martin L" uniqKey="Hibberd M" first="Martin L" last="Hibberd">Martin L. Hibberd</name><name sortKey="Lim, Siew Lan" sort="Lim, Siew Lan" uniqKey="Lim S" first="Siew Lan" last="Lim">Siew Lan Lim</name><name sortKey="Ling, Ai Ee" sort="Ling, Ai Ee" uniqKey="Ling A" first="Ai Ee" last="Ling">Ai Ee Ling</name><name sortKey="Liu, Edison T" sort="Liu, Edison T" uniqKey="Liu E" first="Edison T" last="Liu">Edison T. Liu</name><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><name sortKey="Ng, Lisa F P" sort="Ng, Lisa F P" uniqKey="Ng L" first="Lisa F. P" last="Ng">Lisa F. P. Ng</name><name sortKey="Ruan, Yijun" sort="Ruan, Yijun" uniqKey="Ruan Y" first="Yijun" last="Ruan">Yijun Ruan</name><name sortKey="Stanton, Lawrence W" sort="Stanton, Lawrence W" uniqKey="Stanton L" first="Lawrence W" last="Stanton">Lawrence W. Stanton</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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