The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists
Identifieur interne : 001E85 ( Main/Exploration ); précédent : 001E84; suivant : 001E86The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists
Auteurs : Yang Yang [République populaire de Chine] ; Ling Zhang [République populaire de Chine] ; Heyuan Geng [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Baoying Huang [République populaire de Chine] ; Yin Guo [République populaire de Chine] ; Zhengdong Zhao [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]Source :
- Protein & Cell [ 1674-800X ] ; 2013.
Descripteurs français
- KwdFr :
- Cadres ouverts de lecture, Coronavirus (génétique), Coronavirus (pathogénicité), Gènes viraux, Humains, Interférons (antagonistes et inhibiteurs), Lignée cellulaire, Protéines de la matrice virale (génétique), Protéines de la matrice virale (métabolisme), Protéines recombinantes (génétique), Protéines recombinantes (métabolisme), Protéines virales régulatrices ou accessoires (génétique), Protéines virales régulatrices ou accessoires (métabolisme), Protéines virales structurales (génétique), Protéines virales structurales (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Interférons.
- génétique : Coronavirus, Protéines de la matrice virale, Protéines recombinantes, Protéines virales régulatrices ou accessoires, Protéines virales structurales.
- métabolisme : Protéines de la matrice virale, Protéines recombinantes, Protéines virales régulatrices ou accessoires, Protéines virales structurales.
- pathogénicité : Coronavirus.
- Cadres ouverts de lecture, Gènes viraux, Humains, Lignée cellulaire.
English descriptors
- KwdEn :
- Cell Line, Coronavirus (genetics), Coronavirus (pathogenicity), Genes, Viral, Humans, Interferons (antagonists & inhibitors), Open Reading Frames, Recombinant Proteins (genetics), Recombinant Proteins (metabolism), Viral Matrix Proteins (genetics), Viral Matrix Proteins (metabolism), Viral Regulatory and Accessory Proteins (genetics), Viral Regulatory and Accessory Proteins (metabolism), Viral Structural Proteins (genetics), Viral Structural Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Interferons.
- genetics : Coronavirus, Recombinant Proteins, Viral Matrix Proteins, Viral Regulatory and Accessory Proteins, Viral Structural Proteins.
- chemical , metabolism : Recombinant Proteins, Viral Matrix Proteins, Viral Regulatory and Accessory Proteins, Viral Structural Proteins.
- pathogenicity : Coronavirus.
- Cell Line, Genes, Viral, Humans, Open Reading Frames.
Abstract
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with pathogenic mechanisms that may be driven by innate immune pathways. The goal of this study is to characterize the expression of the structural (S, E, M, N) and accessory (ORF 3, ORF 4a, ORF 4b, ORF 5) proteins of MERS-CoV and to determine whether any of these proteins acts as an interferon antagonist. Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells, and their native expression and subcellular localization were assessed using Wes tern blotting and indirect immunofluorescence. While ORF 4b demonstrated majorly nuclear localization, all of the other proteins demonstrated cytoplasmic localization. In addition, for the first time, our experiments revealed that the M, ORF 4a, ORF 4b, and ORF 5 proteins are potent interferon antagonists. Further examination revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production (IFN-β promoter activity, IRF-3/7 and NF-κB activation) and ISRE promoter element signaling pathways. Together, our results provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.
Url:
DOI: 10.1007/s13238-013-3096-8
PubMed: 24318862
PubMed Central: 4875403
Affiliations:
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Le document en format XML
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when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line</term><term>Coronavirus (genetics)</term><term>Coronavirus (pathogenicity)</term><term>Genes, Viral</term><term>Humans</term><term>Interferons (antagonists & inhibitors)</term><term>Open Reading Frames</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (metabolism)</term><term>Viral Matrix Proteins (genetics)</term><term>Viral Matrix Proteins (metabolism)</term><term>Viral Regulatory and Accessory Proteins (genetics)</term><term>Viral Regulatory and Accessory Proteins (metabolism)</term><term>Viral Structural Proteins (genetics)</term><term>Viral Structural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cadres ouverts de lecture</term><term>Coronavirus (génétique)</term><term>Coronavirus (pathogénicité)</term><term>Gènes viraux</term><term>Humains</term><term>Interférons (antagonistes et inhibiteurs)</term><term>Lignée cellulaire</term><term>Protéines de la matrice virale (génétique)</term><term>Protéines de la matrice virale (métabolisme)</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (métabolisme)</term><term>Protéines virales régulatrices ou accessoires (génétique)</term><term>Protéines virales régulatrices ou accessoires (métabolisme)</term><term>Protéines virales structurales (génétique)</term><term>Protéines virales structurales (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interferons</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term><term>Recombinant Proteins</term><term>Viral Matrix Proteins</term><term>Viral Regulatory and Accessory Proteins</term><term>Viral Structural Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus</term><term>Protéines de la matrice virale</term><term>Protéines recombinantes</term><term>Protéines virales régulatrices ou accessoires</term><term>Protéines virales structurales</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Recombinant Proteins</term><term>Viral Matrix Proteins</term><term>Viral Regulatory and Accessory Proteins</term><term>Viral Structural Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de la matrice virale</term><term>Protéines recombinantes</term><term>Protéines virales régulatrices ou accessoires</term><term>Protéines virales structurales</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Genes, Viral</term><term>Humans</term><term>Open Reading Frames</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cadres ouverts de lecture</term><term>Gènes viraux</term><term>Humains</term><term>Lignée cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with pathogenic mechanisms that may be driven by innate immune pathways. The goal of this study is to characterize the expression of the structural (S, E, M, N) and accessory (ORF 3, ORF 4a, ORF 4b, ORF 5) proteins of MERS-CoV and to determine whether any of these proteins acts as an interferon antagonist. Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells, and their native expression and subcellular localization were assessed using Wes tern blotting and indirect immunofluorescence. While ORF 4b demonstrated majorly nuclear localization, all of the other proteins demonstrated cytoplasmic localization. In addition, for the first time, our experiments revealed that the M, ORF 4a, ORF 4b, and ORF 5 proteins are potent interferon antagonists. Further examination revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production (IFN-β promoter activity, IRF-3/7 and NF-κB activation) and ISRE promoter element signaling pathways. Together, our results provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Basler, Cf" uniqKey="Basler C">CF Basler</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Muhlberger, E" uniqKey="Muhlberger E">E Mühlberger</name></author><author><name sortKey="Volchkov, V" uniqKey="Volchkov V">V Volchkov</name></author><author><name sortKey="Paragas, J" uniqKey="Paragas J">J Paragas</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Breban, R" uniqKey="Breban R">R Breban</name></author><author><name sortKey="Riou, J" uniqKey="Riou J">J Riou</name></author><author><name sortKey="Fontanet, A" uniqKey="Fontanet A">A 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Rooijen</name></author><author><name sortKey="Weiss, Sr" uniqKey="Weiss S">SR Weiss</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name></noRegion><name sortKey="Deng, Yao" sort="Deng, Yao" uniqKey="Deng Y" first="Yao" last="Deng">Yao Deng</name><name sortKey="Geng, Heyuan" sort="Geng, Heyuan" uniqKey="Geng H" first="Heyuan" last="Geng">Heyuan Geng</name><name sortKey="Guo, Yin" sort="Guo, Yin" uniqKey="Guo Y" first="Yin" last="Guo">Yin Guo</name><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Zhang, Ling" sort="Zhang, Ling" uniqKey="Zhang L" first="Ling" last="Zhang">Ling Zhang</name><name sortKey="Zhao, Zhengdong" sort="Zhao, Zhengdong" uniqKey="Zhao Z" first="Zhengdong" last="Zhao">Zhengdong Zhao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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