Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design
Identifieur interne : 000232 ( Pmc/Checkpoint ); précédent : 000231; suivant : 000233Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design
Auteurs : Jeong Yoon Lee ; Sojung Bae ; Jinjong MyoungSource :
- Journal of Microbiology (Seoul, Korea) [ 1225-8873 ] ; 2019.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.
Url:
DOI: 10.1007/s12275-019-9272-7
PubMed: 31452044
PubMed Central: 7091237
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design</title><author><name sortKey="Lee, Jeong Yoon" sort="Lee, Jeong Yoon" uniqKey="Lee J" first="Jeong Yoon" last="Lee">Jeong Yoon Lee</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Bae, Sojung" sort="Bae, Sojung" uniqKey="Bae S" first="Sojung" last="Bae">Sojung Bae</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Myoung, Jinjong" sort="Myoung, Jinjong" uniqKey="Myoung J" first="Jinjong" last="Myoung">Jinjong Myoung</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31452044</idno><idno type="pmc">7091237</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091237</idno><idno type="RBID">PMC:7091237</idno><idno type="doi">10.1007/s12275-019-9272-7</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000390</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000390</idno><idno type="wicri:Area/Pmc/Curation">000390</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000390</idno><idno type="wicri:Area/Pmc/Checkpoint">000232</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000232</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design</title><author><name sortKey="Lee, Jeong Yoon" sort="Lee, Jeong Yoon" uniqKey="Lee J" first="Jeong Yoon" last="Lee">Jeong Yoon Lee</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Bae, Sojung" sort="Bae, Sojung" uniqKey="Bae S" first="Sojung" last="Bae">Sojung Bae</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Myoung, Jinjong" sort="Myoung, Jinjong" uniqKey="Myoung J" first="Jinjong" last="Myoung">Jinjong Myoung</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Microbiology (Seoul, Korea)</title><idno type="ISSN">1225-8873</idno><idno type="eISSN">1976-3794</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abdul Rasool, S" uniqKey="Abdul Rasool S">S Abdul-Rasool</name></author><author><name sortKey="Fielding, Bc" uniqKey="Fielding B">BC Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akira, S" uniqKey="Akira S">S Akira</name></author><author><name sortKey="Uematsu, S" uniqKey="Uematsu S">S Uematsu</name></author><author><name sortKey="Takeuchi, O" uniqKey="Takeuchi O">O Takeuchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alraddadi, Bm" uniqKey="Alraddadi B">BM Alraddadi</name></author><author><name sortKey="Watson, Jt" uniqKey="Watson J">JT Watson</name></author><author><name sortKey="Almarashi, A" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Microbiol</journal-id><journal-id journal-id-type="iso-abbrev">J. Microbiol</journal-id><journal-title-group><journal-title>Journal of Microbiology (Seoul, Korea)</journal-title></journal-title-group><issn pub-type="ppub">1225-8873</issn><issn pub-type="epub">1976-3794</issn><publisher><publisher-name>The Microbiological Society of Korea</publisher-name><publisher-loc>Seoul</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31452044</article-id><article-id pub-id-type="pmc">7091237</article-id><article-id pub-id-type="publisher-id">9272</article-id><article-id pub-id-type="doi">10.1007/s12275-019-9272-7</article-id><article-categories><subj-group subj-group-type="heading"><subject>Microbial Pathogenesis and Host-Microbe Interaction</subject></subj-group></article-categories><title-group><article-title>Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Jeong Yoon</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Bae</surname><given-names>Sojung</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Myoung</surname><given-names>Jinjong</given-names></name><address><phone>+82-63-900-4055</phone><fax>+82-63-900-4012</fax><email>Jinjong.myoung@jbnu.ac.kr</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 4320</institution-id><institution-id institution-id-type="GRID">grid.411545.0</institution-id><institution>Korea Zoonosis Research Institute, Genetic Engineering Research Institute & Department of Bioactive Material Science, College of Natural Science,</institution><institution>Chonbuk National University,</institution></institution-wrap>Jeonju, 54531 Republic of Korea</aff></contrib-group><pub-date pub-type="epub"><day>27</day><month>8</month><year>2019</year></pub-date><pub-date pub-type="ppub"><year>2019</year></pub-date><volume>57</volume><issue>9</issue><fpage>803</fpage><lpage>811</lpage><history><date date-type="received"><day>3</day><month>6</month><year>2019</year></date><date date-type="rev-recd"><day>14</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>17</day><month>6</month><year>2019</year></date></history><permissions><copyright-statement>© The Microbiological Society of Korea 2019</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.</p></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>accessory protein</kwd><kwd>interferon beta</kwd><kwd>MERS-CoV</kwd><kwd>ORF8b</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Microbiological Society of Korea and Springer Nature B.V. 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Bae, Sojung" sort="Bae, Sojung" uniqKey="Bae S" first="Sojung" last="Bae">Sojung Bae</name><name sortKey="Lee, Jeong Yoon" sort="Lee, Jeong Yoon" uniqKey="Lee J" first="Jeong Yoon" last="Lee">Jeong Yoon Lee</name><name sortKey="Myoung, Jinjong" sort="Myoung, Jinjong" uniqKey="Myoung J" first="Jinjong" last="Myoung">Jinjong Myoung</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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