Significance of the Myxovirus Resistance A (MxA) Gene -123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection
Identifieur interne : 002963 ( Main/Merge ); précédent : 002962; suivant : 002964Significance of the Myxovirus Resistance A (MxA) Gene -123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection
Auteurs : Johannes Chi-Yun Ching [Hong Kong] ; Kelvin Yuen Kwong Chan [Hong Kong] ; Eric Hing Leung Lee [Hong Kong] ; Mei-Shu Xu [Hong Kong] ; Campbell Kam Po Ting [Hong Kong] ; Thomas M. K. So [Hong Kong] ; Pak C. Sham [Hong Kong] ; Gabriel M. Leung [Hong Kong] ; Joseph S. M. Peiris [Hong Kong] ; Ui-Soon Khoo [Hong Kong]Source :
- The Journal of infectious diseases [ 0022-1899 ] ; 2010.
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Abstract
Myxovirus resistance A (MxA) is an antiviral protein induced by interferon α and β (IFN-α, If-β) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-α and IFN-β treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-β-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-β stimulation. Endogenous IFN-α and IFN-β induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minor-allele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-α and IFN-β induction such as SARS coronavirus.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Significance of the Myxovirus Resistance A (MxA) Gene -123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection</title><author><name sortKey="Ching, Johannes Chi Yun" sort="Ching, Johannes Chi Yun" uniqKey="Ching J" first="Johannes Chi-Yun" last="Ching">Johannes Chi-Yun Ching</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Yuen Kwong Chan, Kelvin" sort="Yuen Kwong Chan, Kelvin" uniqKey="Yuen Kwong Chan K" first="Kelvin" last="Yuen Kwong Chan">Kelvin Yuen Kwong Chan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Hing Leung Lee, Eric" sort="Hing Leung Lee, Eric" uniqKey="Hing Leung Lee E" first="Eric" last="Hing Leung Lee">Eric Hing Leung Lee</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Mei Shu" sort="Xu, Mei Shu" uniqKey="Xu M" first="Mei-Shu" last="Xu">Mei-Shu Xu</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Kam Po Ting, Campbell" sort="Kam Po Ting, Campbell" uniqKey="Kam Po Ting C" first="Campbell" last="Kam Po Ting">Campbell Kam Po Ting</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="So, Thomas M K" sort="So, Thomas M K" uniqKey="So T" first="Thomas M. 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Peiris</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Microbiology, University of Hong Kong</s1><s3>HKG</s3><sZ>9 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Microbiology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Khoo, Ui Soon" sort="Khoo, Ui Soon" uniqKey="Khoo U" first="Ui-Soon" last="Khoo">Ui-Soon Khoo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0302334</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0302334 INIST</idno><idno type="RBID">Pascal:10-0302334</idno><idno type="wicri:Area/PascalFrancis/Corpus">000152</idno><idno type="wicri:Area/PascalFrancis/Curation">000836</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000131</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000131</idno><idno type="wicri:doubleKey">0022-1899:2010:Ching J:significance:of:the</idno><idno type="wicri:Area/Main/Merge">002963</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Significance of the Myxovirus Resistance A (MxA) Gene -123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection</title><author><name sortKey="Ching, Johannes Chi Yun" sort="Ching, Johannes Chi Yun" uniqKey="Ching J" first="Johannes Chi-Yun" last="Ching">Johannes Chi-Yun Ching</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Yuen Kwong Chan, Kelvin" sort="Yuen Kwong Chan, Kelvin" uniqKey="Yuen Kwong Chan K" first="Kelvin" last="Yuen Kwong Chan">Kelvin Yuen Kwong Chan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Hing Leung Lee, Eric" sort="Hing Leung Lee, Eric" uniqKey="Hing Leung Lee E" first="Eric" last="Hing Leung Lee">Eric Hing Leung Lee</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Mei Shu" sort="Xu, Mei Shu" uniqKey="Xu M" first="Mei-Shu" last="Xu">Mei-Shu Xu</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Kam Po Ting, Campbell" sort="Kam Po Ting, Campbell" uniqKey="Kam Po Ting C" first="Campbell" last="Kam Po Ting">Campbell Kam Po Ting</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="So, Thomas M K" sort="So, Thomas M K" uniqKey="So T" first="Thomas M. K." last="So">Thomas M. K. So</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine and Geriatrics, Princess Margaret Hospital</s1><s3>HKG</s3><sZ>6 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Medicine and Geriatrics, Princess Margaret Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Sham, Pak C" sort="Sham, Pak C" uniqKey="Sham P" first="Pak C." last="Sham">Pak C. Sham</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Psychiatry, University of Hong Kong</s1><s3>HKG</s3><sZ>7 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Psychiatry, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Leung, Gabriel M" sort="Leung, Gabriel M" uniqKey="Leung G" first="Gabriel M." last="Leung">Gabriel M. Leung</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Community Medicine, University of Hong Kong</s1><s3>HKG</s3><sZ>8 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Community Medicine, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Peiris, Joseph S M" sort="Peiris, Joseph S M" uniqKey="Peiris J" first="Joseph S. M." last="Peiris">Joseph S. M. Peiris</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Microbiology, University of Hong Kong</s1><s3>HKG</s3><sZ>9 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Microbiology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Khoo, Ui Soon" sort="Khoo, Ui Soon" uniqKey="Khoo U" first="Ui-Soon" last="Khoo">Ui-Soon Khoo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pathology, University of Hong Kong</s1><s3>HKG</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Pathology, University of Hong Kong</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">The Journal of infectious diseases</title><title level="j" type="abbreviated">J. infect. dis.</title><idno type="ISSN">0022-1899</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">The Journal of infectious diseases</title><title level="j" type="abbreviated">J. infect. dis.</title><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Beta interferon</term><term>Coronavirus</term><term>Gene</term><term>Infection</term><term>Resistance</term><term>Severe acute respiratory syndrome</term><term>Single nucleotide polymorphism</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Résistance</term><term>Gène</term><term>Polymorphisme mononucléotide</term><term>Infection</term><term>Interféron bêta</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Myxovirus resistance A (MxA) is an antiviral protein induced by interferon α and β (IFN-α, If-β) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-α and IFN-β treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-β-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-β stimulation. Endogenous IFN-α and IFN-β induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minor-allele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-α and IFN-β induction such as SARS coronavirus.</div></front></TEI><affiliations><list><country><li>Hong Kong</li></country></list><tree><country name="Hong Kong"><noRegion><name sortKey="Ching, Johannes Chi Yun" sort="Ching, Johannes Chi Yun" uniqKey="Ching J" first="Johannes Chi-Yun" last="Ching">Johannes Chi-Yun Ching</name></noRegion><name sortKey="Hing Leung Lee, Eric" sort="Hing Leung Lee, Eric" uniqKey="Hing Leung Lee E" first="Eric" last="Hing Leung Lee">Eric Hing Leung Lee</name><name sortKey="Kam Po Ting, Campbell" sort="Kam Po Ting, Campbell" uniqKey="Kam Po Ting C" first="Campbell" last="Kam Po Ting">Campbell Kam Po Ting</name><name sortKey="Khoo, Ui Soon" sort="Khoo, Ui Soon" uniqKey="Khoo U" first="Ui-Soon" last="Khoo">Ui-Soon Khoo</name><name sortKey="Leung, Gabriel M" sort="Leung, Gabriel M" uniqKey="Leung G" first="Gabriel M." last="Leung">Gabriel M. Leung</name><name sortKey="Peiris, Joseph S M" sort="Peiris, Joseph S M" uniqKey="Peiris J" first="Joseph S. M." last="Peiris">Joseph S. M. Peiris</name><name sortKey="Sham, Pak C" sort="Sham, Pak C" uniqKey="Sham P" first="Pak C." last="Sham">Pak C. Sham</name><name sortKey="So, Thomas M K" sort="So, Thomas M K" uniqKey="So T" first="Thomas M. K." last="So">Thomas M. K. So</name><name sortKey="Xu, Mei Shu" sort="Xu, Mei Shu" uniqKey="Xu M" first="Mei-Shu" last="Xu">Mei-Shu Xu</name><name sortKey="Yuen Kwong Chan, Kelvin" sort="Yuen Kwong Chan, Kelvin" uniqKey="Yuen Kwong Chan K" first="Kelvin" last="Yuen Kwong Chan">Kelvin Yuen Kwong Chan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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