Nasopharyngeal Shedding of Severe Acute Respiratory Syndrome—Associated Coronavirus Is Associated with Genetic Polymorphisms
Identifieur interne : 004060 ( Main/Exploration ); précédent : 004059; suivant : 004061Nasopharyngeal 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
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse multivariée, Charge virale, Excrétion virale (génétique), Facteur de transcription RelB (génétique), Femelle, Fibrinogène (génétique), Humains, Interleukine-1 (génétique), Interleukine-18 (génétique), Modèles logistiques, Mâle, Partie nasale du pharynx (virologie), Polymorphisme génétique, Sujet âgé, Virus du SRAS (physiologie).
- MESH :
- génétique : Excrétion virale, Facteur de transcription RelB, Fibrinogène, Interleukine-1, Interleukine-18.
- physiologie : Virus du SRAS.
- virologie : Partie nasale du pharynx.
- Adulte, Adulte d'âge moyen, Analyse multivariée, Charge virale, Femelle, Humains, Modèles logistiques, Mâle, Polymorphisme génétique, Sujet âgé.
- Pascal (Inist)
English descriptors
- KwdEn :
- Adult, Aged, Coronavirus, Female, Fibrinogen (genetics), Humans, Interleukin-1 (genetics), Interleukin-18 (genetics), Logistic Models, Male, Middle Aged, Multivariate Analysis, Nasopharynx, Nasopharynx (virology), Polymorphism, Polymorphism, Genetic, SARS Virus (physiology), Severe acute respiratory syndrome, Transcription Factor RelB (genetics), Viral Load, Virus Shedding (genetics).
- MESH :
- chemical , genetics : Fibrinogen, Interleukin-1, Interleukin-18, Transcription Factor RelB.
- genetics : Virus Shedding.
- physiology : SARS Virus.
- virology : Nasopharynx.
- Adult, Aged, Female, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Polymorphism, Genetic, Viral Load.
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).
Url:
- https://api.istex.fr/ark:/67375/HXZ-HB5XDM1W-T/fulltext.pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107974
DOI: 10.1086/503843
Affiliations:
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J." last="Fann">Cathy S. J. Fann</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea><wicri:noRegion>Taipei</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"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea><wicri:noRegion>Taipei</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"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Graduate Institute of Epidemiology, National Taiwan University, Taipei</wicri:regionArea><wicri:noRegion>Taipei</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"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Public Health, National Yang-Ming University, Taipei</wicri:regionArea><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"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Center for Disease Control, Taipei</wicri:regionArea><wicri:noRegion>Taipei</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"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Center for Disease Control, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Liao, Fong" sort="Liao, Fong" uniqKey="Liao F" first="Fong" last="Liao">Fong Liao</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea><wicri:noRegion>Taipei</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"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Graduate Institute of Epidemiology, National Taiwan University, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Public Health, National Yang-Ming University, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Taïwan</country></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Taïwan</country><wicri:regionArea>Reprints or correspondence: Dr. Mei-Shang Ho, IBMS, Academia Sinica, Taipei</wicri:regionArea><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Clinical Infectious Diseases</title><title level="j" type="abbrev">Clinical Infectious Diseases</title><idno type="ISSN">1058-4838</idno><idno type="eISSN">1537-6591</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published">2006</date><biblScope unit="vol">42</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1561">1561</biblScope><biblScope unit="page" to="1569">1569</biblScope></imprint><idno type="ISSN">1058-4838</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1058-4838</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Coronavirus</term><term>Female</term><term>Fibrinogen (genetics)</term><term>Humans</term><term>Interleukin-1 (genetics)</term><term>Interleukin-18 (genetics)</term><term>Logistic Models</term><term>Male</term><term>Middle Aged</term><term>Multivariate Analysis</term><term>Nasopharynx</term><term>Nasopharynx (virology)</term><term>Polymorphism</term><term>Polymorphism, Genetic</term><term>SARS Virus (physiology)</term><term>Severe acute respiratory syndrome</term><term>Transcription Factor RelB (genetics)</term><term>Viral Load</term><term>Virus Shedding (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse multivariée</term><term>Charge virale</term><term>Excrétion virale (génétique)</term><term>Facteur de transcription RelB (génétique)</term><term>Femelle</term><term>Fibrinogène (génétique)</term><term>Humains</term><term>Interleukine-1 (génétique)</term><term>Interleukine-18 (génétique)</term><term>Modèles logistiques</term><term>Mâle</term><term>Partie nasale du pharynx (virologie)</term><term>Polymorphisme génétique</term><term>Sujet âgé</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Fibrinogen</term><term>Interleukin-1</term><term>Interleukin-18</term><term>Transcription Factor RelB</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Virus Shedding</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Excrétion virale</term><term>Facteur de transcription RelB</term><term>Fibrinogène</term><term>Interleukine-1</term><term>Interleukine-18</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Partie nasale du pharynx</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Nasopharynx</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Female</term><term>Humans</term><term>Logistic Models</term><term>Male</term><term>Middle Aged</term><term>Multivariate Analysis</term><term>Polymorphism, Genetic</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse multivariée</term><term>Charge virale</term><term>Femelle</term><term>Humains</term><term>Modèles logistiques</term><term>Mâle</term><term>Polymorphisme génétique</term><term>Sujet âgé</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Nasopharynx</term><term>Polymorphisme</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="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).</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="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="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="Liao, Fong" sort="Liao, Fong" uniqKey="Liao F" first="Fong" last="Liao">Fong Liao</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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