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 : 000B87 ( Pmc/Checkpoint ); précédent : 000B86; suivant : 000B88Significance 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 ; Kelvin Yuen Kwong Chan ; Eric Hing Leung Lee ; Mei-Shu Xu ; Campbell Kam Po Ting ; Thomas M. K. So ; Pak C. Sham ; Gabriel M. Leung ; Joseph S. M. Peiris ; Ui-Soon KhooSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2010.
Abstract
Myxovirus resistance A (MxA) is an antiviral protein induced by interferon α and β (IFN-α, IFN-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 minorallele 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.
Url:
DOI: 10.1086/652799
PubMed: 20462354
PubMed Central: 7109798
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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><nlm:aff id="a1"></nlm:aff></affiliation></author><author><name sortKey="Chan, Kelvin Yuen Kwong" sort="Chan, Kelvin Yuen Kwong" uniqKey="Chan K" first="Kelvin Yuen Kwong" last="Chan">Kelvin Yuen Kwong Chan</name><affiliation><nlm:aff id="a1"></nlm:aff></affiliation></author><author><name sortKey="Lee, Eric Hing Leung" sort="Lee, Eric Hing Leung" uniqKey="Lee E" first="Eric Hing Leung" last="Lee">Eric Hing Leung Lee</name><affiliation><nlm:aff id="a1"></nlm:aff></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><nlm:aff id="a1"></nlm:aff></affiliation></author><author><name sortKey="Ting, Campbell Kam Po" sort="Ting, Campbell Kam Po" uniqKey="Ting C" first="Campbell Kam Po" last="Ting">Campbell Kam Po Ting</name><affiliation><nlm:aff id="a1"></nlm:aff></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><nlm:aff id="a5"></nlm:aff></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><nlm:aff id="a2"></nlm:aff></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><nlm:aff id="a3"></nlm:aff></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><nlm:aff id="a4"></nlm:aff></affiliation></author><author><name sortKey="Khoo, Ui Soon" sort="Khoo, Ui Soon" uniqKey="Khoo U" first="Ui-Soon" last="Khoo">Ui-Soon Khoo</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20462354</idno><idno type="pmc">7109798</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109798</idno><idno type="RBID">PMC:7109798</idno><idno type="doi">10.1086/652799</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">001170</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001170</idno><idno type="wicri:Area/Pmc/Curation">001170</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001170</idno><idno type="wicri:Area/Pmc/Checkpoint">000B87</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000B87</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">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><nlm:aff id="a1"></nlm:aff></affiliation></author><author><name sortKey="Chan, Kelvin Yuen Kwong" sort="Chan, Kelvin Yuen Kwong" uniqKey="Chan K" first="Kelvin Yuen Kwong" last="Chan">Kelvin Yuen Kwong Chan</name><affiliation><nlm:aff id="a1"></nlm:aff></affiliation></author><author><name sortKey="Lee, Eric Hing Leung" sort="Lee, Eric Hing Leung" uniqKey="Lee E" first="Eric Hing Leung" last="Lee">Eric Hing Leung Lee</name><affiliation><nlm:aff id="a1"></nlm:aff></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><nlm:aff id="a1"></nlm:aff></affiliation></author><author><name sortKey="Ting, Campbell Kam Po" sort="Ting, Campbell Kam Po" uniqKey="Ting C" first="Campbell Kam Po" last="Ting">Campbell Kam Po Ting</name><affiliation><nlm:aff id="a1"></nlm:aff></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><nlm:aff id="a5"></nlm:aff></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><nlm:aff id="a2"></nlm:aff></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><nlm:aff id="a3"></nlm:aff></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><nlm:aff id="a4"></nlm:aff></affiliation></author><author><name sortKey="Khoo, Ui Soon" sort="Khoo, Ui Soon" uniqKey="Khoo U" first="Ui-Soon" last="Khoo">Ui-Soon Khoo</name></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>Myxovirus resistance A (MxA) is an antiviral protein induced by interferon α and β (IFN-α, IFN-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 minorallele 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><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="Cheng, Vc" uniqKey="Cheng V">VC Cheng</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id><journal-id journal-id-type="hwp">jinfdis</journal-id><journal-id journal-id-type="publisher-id">jid</journal-id><journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">0022-1899</issn><issn pub-type="epub">1537-6613</issn><publisher><publisher-name>The University of Chicago Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20462354</article-id><article-id pub-id-type="pmc">7109798</article-id><article-id pub-id-type="doi">10.1086/652799</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles And Brief Reports</subject><subj-group subj-group-type="category-toc-heading"><subject>Viruses</subject><subj-group subj-group-type="category-toc-heading"><subject>Major Articles</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>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</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ching</surname><given-names>Johannes Chi-Yun</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Kelvin Yuen Kwong</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Eric Hing Leung</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Mei-Shu</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ting</surname><given-names>Campbell Kam Po</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>So</surname><given-names>Thomas M. K.</given-names></name><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Sham</surname><given-names>Pak C.</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Leung</surname><given-names>Gabriel M.</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Peiris</surname><given-names>Joseph S. M.</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Khoo</surname><given-names>Ui-Soon</given-names></name><xref ref-type="corresp" rid="cor1"></xref><pmc-comment>uskhoo@pathology.hku.hk </pmc-comment>
</contrib></contrib-group><aff id="a1"><label><sup>1</sup></label><institution>Department of Pathology, University of Hong Kong</institution>,<addr-line>Hong Kong</addr-line></aff><aff id="a2"><label><sup>2</sup></label><institution>Department of Psychiatry, University of Hong Kong</institution>,<addr-line>Hong Kong</addr-line></aff><aff id="a3"><label><sup>3</sup></label><institution>Department of Community Medicine, University of Hong Kong</institution>,<addr-line>Hong Kong</addr-line></aff><aff id="a4"><label><sup>4</sup></label><institution>Department of Microbiology, University of Hong Kong</institution>,<addr-line>Hong Kong</addr-line></aff><aff id="a5"><label><sup>5</sup></label><institution>Department of Medicine and Geriatrics, Princess Margaret Hospital</institution>,<addr-line>Hong Kong</addr-line></aff><author-notes><corresp id="cor1">Reprints or correspondence: Dr Ui-Soon Khoo FRCPath Rm 324 3/F University Pathology Building Department of Pathology The University of Hong Kong Queen Mary Hospital Pokfulam Rd Hong Kong (<email>uskhoo@pathology.hku.hk</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>6</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>15</day><month>6</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>6</month><year>2010</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>201</volume><issue>12</issue><fpage>1899</fpage><lpage>1908</lpage><history><date date-type="received"><day>2</day><month>8</month><year>2009</year></date><date date-type="accepted"><day>6</day><month>1</month><year>2010</year></date></history><permissions><copyright-statement>© 2010 by the Infectious Diseases Society of America</copyright-statement><copyright-year>2010</copyright-year><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p></license></permissions><self-uri xlink:href="201-12-1899.pdf"></self-uri><abstract><title>Abstract</title><p>Myxovirus resistance A (MxA) is an antiviral protein induced by interferon α and β (IFN-α, IFN-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 minorallele 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.</p></abstract></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Chan, Kelvin Yuen Kwong" sort="Chan, Kelvin Yuen Kwong" uniqKey="Chan K" first="Kelvin Yuen Kwong" last="Chan">Kelvin Yuen Kwong Chan</name><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><name sortKey="Khoo, Ui Soon" sort="Khoo, Ui Soon" uniqKey="Khoo U" first="Ui-Soon" last="Khoo">Ui-Soon Khoo</name><name sortKey="Lee, Eric Hing Leung" sort="Lee, Eric Hing Leung" uniqKey="Lee E" first="Eric Hing Leung" last="Lee">Eric Hing Leung Lee</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="Ting, Campbell Kam Po" sort="Ting, Campbell Kam Po" uniqKey="Ting C" first="Campbell Kam Po" last="Ting">Campbell Kam Po Ting</name><name sortKey="Xu, Mei Shu" sort="Xu, Mei Shu" uniqKey="Xu M" first="Mei-Shu" last="Xu">Mei-Shu Xu</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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