Activation of c-jun N-terminal kinase upon influenza A virus (IAV) infection is independent of pathogen-related receptors but dependent on amino acid sequence variations of IAV NS1.
Identifieur interne : 000F61 ( Main/Exploration ); précédent : 000F60; suivant : 000F62Activation of c-jun N-terminal kinase upon influenza A virus (IAV) infection is independent of pathogen-related receptors but dependent on amino acid sequence variations of IAV NS1.
Auteurs : Wolfgang Nacken [Allemagne] ; Darisuren Anhlan [Allemagne] ; Eike R. Hrincius [Allemagne] ; Ahmed Mostafa [Égypte] ; Thorsten Wolff [Allemagne] ; Anne Sadewasser [Allemagne] ; Stephan Pleschka [Allemagne] ; Christina Ehrhardt [Allemagne] ; Stephan Ludwig [Allemagne]Source :
- Journal of virology [ 1098-5514 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Cellules HEK293, Cellules rénales canines Madin-Darby, Chiens, DEAD-box RNA helicases (génétique), DEAD-box RNA helicases (métabolisme), Facteur de différenciation myéloïde-88 (génétique), Facteur de différenciation myéloïde-88 (métabolisme), Grippe humaine (génétique), Grippe humaine (métabolisme), Grippe humaine (virologie), Humains, Infections à Orthomyxoviridae (génétique), Infections à Orthomyxoviridae (métabolisme), Infections à Orthomyxoviridae (virologie), JNK Mitogen-Activated Protein Kinases (génétique), JNK Mitogen-Activated Protein Kinases (métabolisme), Lignée cellulaire, Mutagenèse dirigée (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Séquence d'acides aminés (génétique), Transduction du signal (génétique), Trétinoïne (métabolisme), Virus de la grippe A (génétique), Virus de la grippe A (métabolisme).
- MESH :
- génétique : DEAD-box RNA helicases, Facteur de différenciation myéloïde-88, Grippe humaine, Infections à Orthomyxoviridae, JNK Mitogen-Activated Protein Kinases, Protéines virales non structurales, Séquence d'acides aminés, Transduction du signal, Virus de la grippe A.
- métabolisme : DEAD-box RNA helicases, Facteur de différenciation myéloïde-88, Grippe humaine, Infections à Orthomyxoviridae, JNK Mitogen-Activated Protein Kinases, Protéines virales non structurales, Trétinoïne, Virus de la grippe A.
- virologie : Grippe humaine, Infections à Orthomyxoviridae.
- Animaux, Cellules HEK293, Cellules rénales canines Madin-Darby, Chiens, Humains, Lignée cellulaire, Mutagenèse dirigée.
English descriptors
- KwdEn :
- Amino Acid Sequence (genetics), Animals, Cell Line, DEAD-box RNA Helicases (genetics), DEAD-box RNA Helicases (metabolism), Dogs, HEK293 Cells, Humans, Influenza A virus (genetics), Influenza A virus (metabolism), Influenza, Human (genetics), Influenza, Human (metabolism), Influenza, Human (virology), JNK Mitogen-Activated Protein Kinases (genetics), JNK Mitogen-Activated Protein Kinases (metabolism), Madin Darby Canine Kidney Cells, Mutagenesis, Site-Directed (methods), Myeloid Differentiation Factor 88 (genetics), Myeloid Differentiation Factor 88 (metabolism), Orthomyxoviridae Infections (genetics), Orthomyxoviridae Infections (metabolism), Orthomyxoviridae Infections (virology), Signal Transduction (genetics), Tretinoin (metabolism), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , genetics : DEAD-box RNA Helicases, JNK Mitogen-Activated Protein Kinases, Myeloid Differentiation Factor 88, Viral Nonstructural Proteins.
- genetics : Amino Acid Sequence, Influenza A virus, Influenza, Human, Orthomyxoviridae Infections, Signal Transduction.
- chemical , metabolism : DEAD-box RNA Helicases, Influenza A virus, Influenza, Human, JNK Mitogen-Activated Protein Kinases, Myeloid Differentiation Factor 88, Orthomyxoviridae Infections, Tretinoin, Viral Nonstructural Proteins.
- methods : Mutagenesis, Site-Directed.
- virology : Influenza, Human, Orthomyxoviridae Infections.
- Animals, Cell Line, Dogs, HEK293 Cells, Humans, Madin Darby Canine Kidney Cells.
Abstract
A hallmark cell response to influenza A virus (IAV) infections is the phosphorylation and activation of c-jun N-terminal kinase (JNK). However, so far it is not fully clear which molecules are involved in the activation of JNK upon IAV infection. Here, we report that the transfection of influenza viral-RNA induces JNK in a retinoic acid-inducible gene I (RIG-I)-dependent manner. However, neither RIG-I-like receptors nor MyD88-dependent Toll-like receptors were found to be involved in the activation of JNK upon IAV infection. Viral JNK activation may be blocked by addition of cycloheximide and heat shock protein inhibitors during infection, suggesting that the expression of an IAV-encoded protein is responsible for JNK activation. Indeed, the overexpression of nonstructural protein 1 (NS1) of certain IAV subtypes activated JNK, whereas those of some other subtypes failed to activate JNK. Site-directed mutagenesis experiments using NS1 of the IAV H7N7, H5N1, and H3N2 subtypes identified the amino acid residue phenylalanine (F) at position 103 to be decisive for JNK activation. Cleavage- and polyadenylation-specific factor 30 (CPSF30), whose binding to NS1 is stabilized by the amino acids F103 and M106, is not involved in JNK activation. Conclusively, subtype-specific sequence variations in the IAV NS1 protein result in subtype-specific differences in JNK signaling upon IAV infection.
DOI: 10.1128/JVI.00424-14
PubMed: 24872593
Affiliations:
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Le document en format XML
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first="Christina" last="Ehrhardt">Christina Ehrhardt</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany Cells in Motion Cluster of Excellence, University of Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany Cells in Motion Cluster of Excellence, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Ludwig, Stephan" sort="Ludwig, Stephan" uniqKey="Ludwig S" first="Stephan" last="Ludwig">Stephan 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receptors but dependent on amino acid sequence variations of IAV NS1.</title><author><name sortKey="Nacken, Wolfgang" sort="Nacken, Wolfgang" uniqKey="Nacken W" first="Wolfgang" last="Nacken">Wolfgang Nacken</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Anhlan, Darisuren" sort="Anhlan, Darisuren" uniqKey="Anhlan D" first="Darisuren" last="Anhlan">Darisuren Anhlan</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Hrincius, Eike R" sort="Hrincius, Eike R" uniqKey="Hrincius E" first="Eike R" last="Hrincius">Eike R. Hrincius</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name><affiliation wicri:level="1"><nlm:affiliation>Virology Laboratory, National Research Center, Cairo, Egypt.</nlm:affiliation><country xml:lang="fr">Égypte</country><wicri:regionArea>Virology Laboratory, National Research Center, Cairo</wicri:regionArea><wicri:noRegion>Cairo</wicri:noRegion></affiliation></author><author><name sortKey="Wolff, Thorsten" sort="Wolff, Thorsten" uniqKey="Wolff T" first="Thorsten" last="Wolff">Thorsten Wolff</name><affiliation wicri:level="3"><nlm:affiliation>Division of Influenza and other Respiratory Viruses, Robert Koch Institute (RKI), Berlin, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Influenza and other Respiratory Viruses, Robert Koch Institute (RKI), Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Sadewasser, Anne" sort="Sadewasser, Anne" uniqKey="Sadewasser A" first="Anne" last="Sadewasser">Anne Sadewasser</name><affiliation wicri:level="3"><nlm:affiliation>Division of Influenza and other Respiratory Viruses, Robert Koch Institute (RKI), Berlin, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Influenza and other Respiratory Viruses, Robert Koch Institute (RKI), Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Pleschka, Stephan" sort="Pleschka, Stephan" uniqKey="Pleschka S" first="Stephan" last="Pleschka">Stephan Pleschka</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Medical Virology, Justus Liebig University Giessen, Giessen</wicri:regionArea><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion><wicri:noRegion>Giessen</wicri:noRegion></affiliation></author><author><name sortKey="Ehrhardt, Christina" sort="Ehrhardt, Christina" uniqKey="Ehrhardt C" first="Christina" last="Ehrhardt">Christina Ehrhardt</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany Cells in Motion Cluster of Excellence, University of Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany Cells in Motion Cluster of Excellence, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Ludwig, Stephan" sort="Ludwig, Stephan" uniqKey="Ludwig S" first="Stephan" last="Ludwig">Stephan Ludwig</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany Cells in Motion Cluster of Excellence, University of Münster, Münster, Germany ludwigs@uni-muenster.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Münster, Germany Cells in Motion Cluster of Excellence, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence (genetics)</term><term>Animals</term><term>Cell Line</term><term>DEAD-box RNA Helicases (genetics)</term><term>DEAD-box RNA Helicases (metabolism)</term><term>Dogs</term><term>HEK293 Cells</term><term>Humans</term><term>Influenza A virus (genetics)</term><term>Influenza A virus (metabolism)</term><term>Influenza, Human (genetics)</term><term>Influenza, Human (metabolism)</term><term>Influenza, Human (virology)</term><term>JNK Mitogen-Activated Protein Kinases (genetics)</term><term>JNK Mitogen-Activated Protein Kinases (metabolism)</term><term>Madin Darby Canine Kidney Cells</term><term>Mutagenesis, Site-Directed (methods)</term><term>Myeloid Differentiation Factor 88 (genetics)</term><term>Myeloid Differentiation Factor 88 (metabolism)</term><term>Orthomyxoviridae Infections (genetics)</term><term>Orthomyxoviridae Infections (metabolism)</term><term>Orthomyxoviridae Infections (virology)</term><term>Signal Transduction (genetics)</term><term>Tretinoin (metabolism)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Nonstructural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>DEAD-box RNA helicases (génétique)</term><term>DEAD-box RNA helicases (métabolisme)</term><term>Facteur de différenciation myéloïde-88 (génétique)</term><term>Facteur de différenciation myéloïde-88 (métabolisme)</term><term>Grippe humaine (génétique)</term><term>Grippe humaine (métabolisme)</term><term>Grippe humaine (virologie)</term><term>Humains</term><term>Infections à Orthomyxoviridae (génétique)</term><term>Infections à Orthomyxoviridae (métabolisme)</term><term>Infections à Orthomyxoviridae (virologie)</term><term>JNK Mitogen-Activated Protein Kinases (génétique)</term><term>JNK Mitogen-Activated Protein Kinases (métabolisme)</term><term>Lignée cellulaire</term><term>Mutagenèse dirigée ()</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Séquence d'acides aminés (génétique)</term><term>Transduction du signal (génétique)</term><term>Trétinoïne (métabolisme)</term><term>Virus de la grippe A (génétique)</term><term>Virus de la grippe A (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DEAD-box RNA Helicases</term><term>JNK Mitogen-Activated Protein Kinases</term><term>Myeloid Differentiation Factor 88</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amino Acid Sequence</term><term>Influenza A virus</term><term>Influenza, Human</term><term>Orthomyxoviridae Infections</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>DEAD-box RNA helicases</term><term>Facteur de différenciation myéloïde-88</term><term>Grippe humaine</term><term>Infections à Orthomyxoviridae</term><term>JNK Mitogen-Activated Protein Kinases</term><term>Protéines virales non structurales</term><term>Séquence d'acides aminés</term><term>Transduction du signal</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DEAD-box RNA Helicases</term><term>Influenza A virus</term><term>Influenza, Human</term><term>JNK Mitogen-Activated Protein Kinases</term><term>Myeloid Differentiation Factor 88</term><term>Orthomyxoviridae Infections</term><term>Tretinoin</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Mutagenesis, Site-Directed</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>DEAD-box RNA helicases</term><term>Facteur de différenciation myéloïde-88</term><term>Grippe humaine</term><term>Infections à Orthomyxoviridae</term><term>JNK Mitogen-Activated Protein Kinases</term><term>Protéines virales non structurales</term><term>Trétinoïne</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term><term>Infections à Orthomyxoviridae</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Dogs</term><term>HEK293 Cells</term><term>Humans</term><term>Madin Darby Canine Kidney Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>Humains</term><term>Lignée cellulaire</term><term>Mutagenèse dirigée</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A hallmark cell response to influenza A virus (IAV) infections is the phosphorylation and activation of c-jun N-terminal kinase (JNK). However, so far it is not fully clear which molecules are involved in the activation of JNK upon IAV infection. Here, we report that the transfection of influenza viral-RNA induces JNK in a retinoic acid-inducible gene I (RIG-I)-dependent manner. However, neither RIG-I-like receptors nor MyD88-dependent Toll-like receptors were found to be involved in the activation of JNK upon IAV infection. Viral JNK activation may be blocked by addition of cycloheximide and heat shock protein inhibitors during infection, suggesting that the expression of an IAV-encoded protein is responsible for JNK activation. Indeed, the overexpression of nonstructural protein 1 (NS1) of certain IAV subtypes activated JNK, whereas those of some other subtypes failed to activate JNK. Site-directed mutagenesis experiments using NS1 of the IAV H7N7, H5N1, and H3N2 subtypes identified the amino acid residue phenylalanine (F) at position 103 to be decisive for JNK activation. Cleavage- and polyadenylation-specific factor 30 (CPSF30), whose binding to NS1 is stabilized by the amino acids F103 and M106, is not involved in JNK activation. Conclusively, subtype-specific sequence variations in the IAV NS1 protein result in subtype-specific differences in JNK signaling upon IAV infection.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Égypte</li></country><region><li>Berlin</li><li>District de Münster</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Berlin</li><li>Münster</li></settlement></list><tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Nacken, Wolfgang" sort="Nacken, Wolfgang" uniqKey="Nacken W" first="Wolfgang" last="Nacken">Wolfgang Nacken</name></region><name sortKey="Anhlan, Darisuren" sort="Anhlan, Darisuren" uniqKey="Anhlan D" first="Darisuren" last="Anhlan">Darisuren Anhlan</name><name sortKey="Ehrhardt, Christina" sort="Ehrhardt, Christina" uniqKey="Ehrhardt C" first="Christina" last="Ehrhardt">Christina Ehrhardt</name><name sortKey="Hrincius, Eike R" sort="Hrincius, Eike R" uniqKey="Hrincius E" first="Eike R" last="Hrincius">Eike R. Hrincius</name><name sortKey="Ludwig, Stephan" sort="Ludwig, Stephan" uniqKey="Ludwig S" first="Stephan" last="Ludwig">Stephan Ludwig</name><name sortKey="Pleschka, Stephan" sort="Pleschka, Stephan" uniqKey="Pleschka S" first="Stephan" last="Pleschka">Stephan Pleschka</name><name sortKey="Sadewasser, Anne" sort="Sadewasser, Anne" uniqKey="Sadewasser A" first="Anne" last="Sadewasser">Anne Sadewasser</name><name sortKey="Wolff, Thorsten" sort="Wolff, Thorsten" uniqKey="Wolff T" first="Thorsten" last="Wolff">Thorsten Wolff</name></country><country name="Égypte"><noRegion><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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