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The membrane protein of SARS-CoV suppresses NF-κB activation

Identifieur interne : 003B15 ( Main/Exploration ); précédent : 003B14; suivant : 003B16

The membrane protein of SARS-CoV suppresses NF-κB activation

Auteurs : XIAONAN FANG [République populaire de Chine] ; JINRONG GAO [République populaire de Chine] ; HONG ZHENG [République populaire de Chine] ; BAOZONG LI [République populaire de Chine] ; LINGBAO KONG [République populaire de Chine] ; YIJUAN ZHANG [République populaire de Chine] ; WEI WANG [République populaire de Chine] ; YINGCHUN ZENG [République populaire de Chine] ; LINBAI YE [République populaire de Chine]

Source :

RBID : Pascal:08-0133886

Descripteurs français

English descriptors

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate IKB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-κB), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKKβ using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-α) induced NF-κB activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-κB activity probably through a direct interaction with IKKβ, resulting in lower Cox-2 expression. Suppression of NF-KB activity and Cox-2 expression may contribute to SARS pathogenesis.


Affiliations:


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<term>Transcription factor NFκB</term>
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<term>Virus syndrome respiratoire aigu sévère</term>
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<div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate IKB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-κB), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKKβ using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-α) induced NF-κB activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-κB activity probably through a direct interaction with IKKβ, resulting in lower Cox-2 expression. Suppression of NF-KB activity and Cox-2 expression may contribute to SARS pathogenesis.</div>
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<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="Xiaonan Fang" sort="Xiaonan Fang" uniqKey="Xiaonan Fang" last="Xiaonan Fang">XIAONAN FANG</name>
</region>
<name sortKey="Baozong Li" sort="Baozong Li" uniqKey="Baozong Li" last="Baozong Li">BAOZONG LI</name>
<name sortKey="Hong Zheng" sort="Hong Zheng" uniqKey="Hong Zheng" last="Hong Zheng">HONG ZHENG</name>
<name sortKey="Jinrong Gao" sort="Jinrong Gao" uniqKey="Jinrong Gao" last="Jinrong Gao">JINRONG GAO</name>
<name sortKey="Jinrong Gao" sort="Jinrong Gao" uniqKey="Jinrong Gao" last="Jinrong Gao">JINRONG GAO</name>
<name sortKey="Linbai Ye" sort="Linbai Ye" uniqKey="Linbai Ye" last="Linbai Ye">LINBAI YE</name>
<name sortKey="Lingbao Kong" sort="Lingbao Kong" uniqKey="Lingbao Kong" last="Lingbao Kong">LINGBAO KONG</name>
<name sortKey="Wei Wang" sort="Wei Wang" uniqKey="Wei Wang" last="Wei Wang">WEI WANG</name>
<name sortKey="Yijuan Zhang" sort="Yijuan Zhang" uniqKey="Yijuan Zhang" last="Yijuan Zhang">YIJUAN ZHANG</name>
<name sortKey="Yingchun Zeng" sort="Yingchun Zeng" uniqKey="Yingchun Zeng" last="Yingchun Zeng">YINGCHUN ZENG</name>
</country>
</tree>
</affiliations>
</record>

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