Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms
Identifieur interne : 004650 ( Main/Merge ); précédent : 004649; suivant : 004651Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms
Auteurs : Wei-Ju Chen [Taïwan] ; Jyh-Yuan Yang [Taïwan] ; Jih-Hui Lin [Taïwan] ; Cathy S. J. Fann [Taïwan] ; Valeriy Osyetrov [Taïwan] ; Chwan-Chuen King [Taïwan] ; Yi-Ming Arthur Chen [Taïwan] ; Hsiao-Ling Chang [Taïwan] ; Hung-Wei Kuo [Taïwan] ; FONG LIAO [Taïwan] ; Mei-Shang Ho [Taïwan]Source :
- Clinical infectious diseases [ 1058-4838 ] ; 2006.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
Background. A high initial or peak severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 108 SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P<.0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P =.0015, by trend test). Virus shedding was found to be higher among male patients (P =.0014, by multivariate logistic regression) and among older patients (P =.015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P =.014) and 1A (P =.031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P =.034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P =.008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).
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W:nasopharyngeal:shedding:of</idno><idno type="wicri:Area/Main/Merge">004650</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms</title><author><name sortKey="Chen, Wei Ju" sort="Chen, Wei Ju" uniqKey="Chen W" first="Wei-Ju" last="Chen">Wei-Ju Chen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1><s3>TWN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Jyh Yuan" sort="Yang, Jyh Yuan" uniqKey="Yang J" first="Jyh-Yuan" last="Yang">Jyh-Yuan Yang</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1><s3>TWN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Jih Hui" sort="Lin, Jih Hui" uniqKey="Lin J" first="Jih-Hui" last="Lin">Jih-Hui Lin</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1><s3>TWN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Fann, Cathy S J" sort="Fann, Cathy S J" uniqKey="Fann C" first="Cathy S. J." last="Fann">Cathy S. J. Fann</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1><s3>TWN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Osyetrov, Valeriy" sort="Osyetrov, Valeriy" uniqKey="Osyetrov V" first="Valeriy" last="Osyetrov">Valeriy Osyetrov</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1><s3>TWN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="King, Chwan Chuen" sort="King, Chwan Chuen" uniqKey="King C" first="Chwan-Chuen" last="King">Chwan-Chuen King</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Graduate Institute of Epidemiology, National Taiwan University</s1><s3>TWN</s3><sZ>6 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Graduate Institute of Epidemiology, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yi Ming Arthur" sort="Chen, Yi Ming Arthur" uniqKey="Chen Y" first="Yi-Ming Arthur" last="Chen">Yi-Ming Arthur Chen</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute of Public Health, National Yang-Ming University</s1><s2>Taipei</s2><s3>TWN</s3><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1><s3>TWN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1><s3>TWN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Fong Liao" sort="Fong Liao" uniqKey="Fong Liao" last="Fong Liao">FONG LIAO</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1><s3>TWN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion></affiliation></author><author><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1><s3>TWN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Graduate Institute of Epidemiology, National Taiwan University</s1><s3>TWN</s3><sZ>6 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Graduate Institute of Epidemiology, National Taiwan University</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute of Public Health, National Yang-Ming University</s1><s2>Taipei</s2><s3>TWN</s3><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Clinical infectious diseases</title><title level="j" type="abbreviated">Clin. infect. dis.</title><idno type="ISSN">1058-4838</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Clinical infectious diseases</title><title level="j" type="abbreviated">Clin. infect. dis.</title><idno type="ISSN">1058-4838</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term><term>Nasopharynx</term><term>Polymorphism</term><term>Severe acute respiratory syndrome</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term><term>Nasopharynx</term><term>Polymorphisme</term><term>Coronavirus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background. A high initial or peak severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 10<sup>8</sup> SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P<.0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P =.0015, by trend test). Virus shedding was found to be higher among male patients (P =.0014, by multivariate logistic regression) and among older patients (P =.015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P =.014) and 1A (P =.031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P =.034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P =.008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).</div></front></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Chen, Wei Ju" sort="Chen, Wei Ju" uniqKey="Chen W" first="Wei-Ju" last="Chen">Wei-Ju Chen</name></noRegion><name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name><name sortKey="Chen, Yi Ming Arthur" sort="Chen, Yi Ming Arthur" uniqKey="Chen Y" first="Yi-Ming Arthur" last="Chen">Yi-Ming Arthur Chen</name><name sortKey="Fann, Cathy S J" sort="Fann, Cathy S J" uniqKey="Fann C" first="Cathy S. J." last="Fann">Cathy S. J. Fann</name><name sortKey="Fong Liao" sort="Fong Liao" uniqKey="Fong Liao" last="Fong Liao">FONG LIAO</name><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name><name sortKey="King, Chwan Chuen" sort="King, Chwan Chuen" uniqKey="King C" first="Chwan-Chuen" last="King">Chwan-Chuen King</name><name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name><name sortKey="Lin, Jih Hui" sort="Lin, Jih Hui" uniqKey="Lin J" first="Jih-Hui" last="Lin">Jih-Hui Lin</name><name sortKey="Osyetrov, Valeriy" sort="Osyetrov, Valeriy" uniqKey="Osyetrov V" first="Valeriy" last="Osyetrov">Valeriy Osyetrov</name><name sortKey="Yang, Jyh Yuan" sort="Yang, Jyh Yuan" uniqKey="Yang J" first="Jyh-Yuan" last="Yang">Jyh-Yuan Yang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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