Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB
Identifieur interne : 000F30 ( Pmc/Checkpoint ); précédent : 000F29; suivant : 000F31Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB
Auteurs : Xue Zhang [République populaire de Chine] ; Kailang Wu [République populaire de Chine] ; Di Wang [République populaire de Chine] ; Xin Yue [République populaire de Chine] ; Degui Song [République populaire de Chine] ; Ying Zhu [République populaire de Chine] ; Jianguo Wu [République populaire de Chine]Source :
- Virology [ 0042-6822 ] ; 2007.
Abstract
High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.
Url:
DOI: 10.1016/j.virol.2007.04.009
PubMed: 17490702
PubMed Central: 7103332
Affiliations:
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China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Wu, Kailang" sort="Wu, Kailang" uniqKey="Wu K" first="Kailang" last="Wu">Kailang Wu</name><affiliation wicri:level="4"><nlm:aff id="aff1">State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Wang, Di" sort="Wang, Di" uniqKey="Wang D" first="Di" last="Wang">Di Wang</name><affiliation wicri:level="4"><nlm:aff id="aff1">State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Yue, Xin" sort="Yue, Xin" uniqKey="Yue X" first="Xin" last="Yue">Xin Yue</name><affiliation wicri:level="4"><nlm:aff id="aff1">State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Song, Degui" sort="Song, Degui" uniqKey="Song D" first="Degui" last="Song">Degui Song</name><affiliation wicri:level="1"><nlm:aff id="aff2">College of Biological Sciences, Guangxi Normal University, Guilin 541004, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>College of Biological Sciences, Guangxi Normal University, Guilin 541004</wicri:regionArea><wicri:noRegion>Guilin 541004</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Ying" sort="Zhu, Ying" uniqKey="Zhu Y" first="Ying" last="Zhu">Ying Zhu</name><affiliation wicri:level="4"><nlm:aff id="aff1">State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Wu, Jianguo" sort="Wu, Jianguo" uniqKey="Wu J" first="Jianguo" last="Wu">Jianguo Wu</name><affiliation wicri:level="4"><nlm:aff id="aff1">State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName><orgName type="university">Université de Wuhan</orgName><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><idno type="eISSN">1096-0341</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Akira, S" uniqKey="Akira S">S. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Virology</journal-id><journal-id journal-id-type="iso-abbrev">Virology</journal-id><journal-title-group><journal-title>Virology</journal-title></journal-title-group><issn pub-type="ppub">0042-6822</issn><issn pub-type="epub">1096-0341</issn><publisher><publisher-name>Elsevier Inc.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17490702</article-id><article-id pub-id-type="pmc">7103332</article-id><article-id pub-id-type="publisher-id">S0042-6822(07)00262-0</article-id><article-id pub-id-type="doi">10.1016/j.virol.2007.04.009</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Xue</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Kailang</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Di</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Yue</surname><given-names>Xin</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Degui</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Zhu</surname><given-names>Ying</given-names></name><email>yingzhu@whu.edu.cn</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Jianguo</given-names></name><email>jwu@whu.edu.cn</email><email>wu9988@vip.sina.com</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="aff1"><label>a</label>State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China</aff><aff id="aff2"><label>b</label>College of Biological Sciences, Guangxi Normal University, Guilin 541004, P.R. China</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding authors. J. Wu is to be contacted at fax: +86 27 68754592. <email>yingzhu@whu.edu.cn</email><email>jwu@whu.edu.cn</email><email>wu9988@vip.sina.com</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>9</day><month>5</month><year>2007</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>1</day><month>9</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>9</day><month>5</month><year>2007</year></pub-date><volume>365</volume><issue>2</issue><fpage>324</fpage><lpage>335</lpage><history><date date-type="received"><day>31</day><month>12</month><year>2006</year></date><date date-type="rev-recd"><day>20</day><month>1</month><year>2007</year></date><date date-type="accepted"><day>9</day><month>4</month><year>2007</year></date></history><permissions><copyright-statement>Copyright © 2007 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2007</copyright-year><copyright-holder>Elsevier Inc.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract><p>High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.</p></abstract><kwd-group><title>Keywords</title><kwd>SARS-CoV</kwd><kwd>N protein</kwd><kwd>Gene regulation</kwd><kwd>Virus infection</kwd><kwd>Pathogenesis</kwd><kwd>IL-6</kwd><kwd>Inflammation</kwd><kwd>NF-κB</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Hubei</li></region><settlement><li>Wuhan</li></settlement><orgName><li>Université de Wuhan</li></orgName></list><tree><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Zhang, Xue" sort="Zhang, Xue" uniqKey="Zhang X" first="Xue" last="Zhang">Xue Zhang</name></region><name sortKey="Song, Degui" sort="Song, Degui" uniqKey="Song D" first="Degui" last="Song">Degui Song</name><name sortKey="Wang, Di" sort="Wang, Di" uniqKey="Wang D" first="Di" last="Wang">Di Wang</name><name sortKey="Wu, Jianguo" sort="Wu, Jianguo" uniqKey="Wu J" first="Jianguo" last="Wu">Jianguo Wu</name><name sortKey="Wu, Kailang" sort="Wu, Kailang" uniqKey="Wu K" first="Kailang" last="Wu">Kailang Wu</name><name sortKey="Yue, Xin" sort="Yue, Xin" uniqKey="Yue X" first="Xin" last="Yue">Xin Yue</name><name sortKey="Zhu, Ying" sort="Zhu, Ying" uniqKey="Zhu Y" first="Ying" last="Zhu">Ying Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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