NF90 exerts antiviral activity through regulation of PKR phosphorylation and stress granules in infected cells.
Identifieur interne : 000F17 ( Main/Exploration ); précédent : 000F16; suivant : 000F18NF90 exerts antiviral activity through regulation of PKR phosphorylation and stress granules in infected cells.
Auteurs : Xi Wen [République populaire de Chine] ; Xiaofeng Huang ; Bobo Wing-Yee Mok ; Yixin Chen ; Min Zheng ; Siu-Ying Lau ; Pui Wang ; Wenjun Song ; Dong-Yan Jin ; Kwok-Yung Yuen ; Honglin ChenSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2014.
Descripteurs français
- KwdFr :
- ARN double brin (génétique), ARN double brin (métabolisme), Activation enzymatique, Animaux, Antiviraux (métabolisme), Expression des gènes, Facteurs nucléaires-90 (génétique), Facteurs nucléaires-90 (métabolisme), Granulations cytoplasmiques (métabolisme), Humains, Interféron bêta (génétique), Interféron bêta (métabolisme), Liaison aux protéines, Modèles biologiques, Mutation, Phosphorylation, Protéines de liaison à l'ARN (génétique), Protéines de liaison à l'ARN (métabolisme), Réplication virale, Stress physiologique, Techniques de knock-down de gènes, Transport de protéines, Virus de la grippe A (génétique), Virus de la grippe A (métabolisme), eIF-2 Kinase (génétique), eIF-2 Kinase (métabolisme).
- MESH :
- génétique : ARN double brin, Facteurs nucléaires-90, Interféron bêta, Protéines de liaison à l'ARN, Virus de la grippe A, eIF-2 Kinase.
- métabolisme : ARN double brin, Antiviraux, Facteurs nucléaires-90, Granulations cytoplasmiques, Interféron bêta, Protéines de liaison à l'ARN, Virus de la grippe A, eIF-2 Kinase.
- Activation enzymatique, Animaux, Expression des gènes, Humains, Liaison aux protéines, Modèles biologiques, Mutation, Phosphorylation, Réplication virale, Stress physiologique, Techniques de knock-down de gènes, Transport de protéines.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (metabolism), Cytoplasmic Granules (metabolism), Enzyme Activation, Gene Expression, Gene Knockdown Techniques, Humans, Influenza A virus (genetics), Influenza A virus (metabolism), Interferon-beta (genetics), Interferon-beta (metabolism), Models, Biological, Mutation, Nuclear Factor 90 Proteins (genetics), Nuclear Factor 90 Proteins (metabolism), Phosphorylation, Protein Binding, Protein Transport, RNA, Double-Stranded (genetics), RNA, Double-Stranded (metabolism), RNA-Binding Proteins (genetics), RNA-Binding Proteins (metabolism), Stress, Physiological, Virus Replication, eIF-2 Kinase (genetics), eIF-2 Kinase (metabolism).
- MESH :
- chemical , genetics : Interferon-beta, Nuclear Factor 90 Proteins, RNA, Double-Stranded, RNA-Binding Proteins, eIF-2 Kinase.
- chemical , metabolism : Antiviral Agents, Interferon-beta, Nuclear Factor 90 Proteins, RNA, Double-Stranded, RNA-Binding Proteins, eIF-2 Kinase.
- genetics : Influenza A virus.
- metabolism : Cytoplasmic Granules, Influenza A virus.
- Animals, Enzyme Activation, Gene Expression, Gene Knockdown Techniques, Humans, Models, Biological, Mutation, Phosphorylation, Protein Binding, Protein Transport, Stress, Physiological, Virus Replication.
Abstract
NF90 was shown to exhibit broad antiviral activity against several viruses, but detailed mechanisms remain unclear. In this study, we examined the molecular basis for the inhibitory effect of NF90 on virus replication mediated through protein kinase (PKR)-associated translational regulation. We first verified the interaction between NF90 and PKR in mammalian cells and showed that NF90 interacts with PKR through its C-terminal and that the interaction is independent of NF90 RNA-binding properties. We further showed that knockdown of NF90 resulted in significantly lower levels of PKR phosphorylation in response to dsRNA induction and influenza virus infection. We also showed that high concentrations of NF90 exhibit negative regulatory effects on PKR phosphorylation, presumably through competition for dsRNA via the C-terminal RNA-binding domain. PKR activation is essential for the formation of stress granules in response to dsRNA induction. Our results showed that NF90 is a component of stress granules. In NF90-knockdown cells, dsRNA treatment induced significantly lower levels of stress granules than in control cells. Further evidence for an NF90-PKR antiviral pathway was obtained using an NS1 mutated influenza A virus specifically attenuated in its ability to inhibit PKR activation. This mutant virus replicated indistinguishably from wild-type virus in NF90-knockdown cells, but not in scrambled control cells or Vero cells, indicating that NF90's antiviral function occurs through interaction with PKR. Taken together, these results reveal a yet-to-be defined host antiviral mechanism in which NF90 upregulation of PKR phosphorylation restricts virus infection.
DOI: 10.4049/jimmunol.1302813
PubMed: 24623135
Affiliations:
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Le document en format XML
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Huang</name></author><author><name sortKey="Mok, Bobo Wing Yee" sort="Mok, Bobo Wing Yee" uniqKey="Mok B" first="Bobo Wing-Yee" last="Mok">Bobo Wing-Yee Mok</name></author><author><name sortKey="Chen, Yixin" sort="Chen, Yixin" uniqKey="Chen Y" first="Yixin" last="Chen">Yixin Chen</name></author><author><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name></author><author><name sortKey="Lau, Siu Ying" sort="Lau, Siu Ying" uniqKey="Lau S" first="Siu-Ying" last="Lau">Siu-Ying Lau</name></author><author><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name></author><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name></author><author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen 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Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Xiaofeng" sort="Huang, Xiaofeng" uniqKey="Huang X" first="Xiaofeng" last="Huang">Xiaofeng Huang</name></author><author><name sortKey="Mok, Bobo Wing Yee" sort="Mok, Bobo Wing Yee" uniqKey="Mok B" first="Bobo Wing-Yee" last="Mok">Bobo Wing-Yee Mok</name></author><author><name sortKey="Chen, Yixin" sort="Chen, Yixin" uniqKey="Chen Y" first="Yixin" last="Chen">Yixin Chen</name></author><author><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name></author><author><name sortKey="Lau, Siu Ying" sort="Lau, Siu Ying" uniqKey="Lau S" first="Siu-Ying" last="Lau">Siu-Ying Lau</name></author><author><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name></author><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name></author><author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name></author></analytic><series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title><idno type="eISSN">1550-6606</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (metabolism)</term><term>Cytoplasmic Granules (metabolism)</term><term>Enzyme Activation</term><term>Gene Expression</term><term>Gene Knockdown Techniques</term><term>Humans</term><term>Influenza A virus (genetics)</term><term>Influenza A virus (metabolism)</term><term>Interferon-beta (genetics)</term><term>Interferon-beta (metabolism)</term><term>Models, Biological</term><term>Mutation</term><term>Nuclear Factor 90 Proteins (genetics)</term><term>Nuclear Factor 90 Proteins (metabolism)</term><term>Phosphorylation</term><term>Protein Binding</term><term>Protein Transport</term><term>RNA, Double-Stranded (genetics)</term><term>RNA, Double-Stranded (metabolism)</term><term>RNA-Binding Proteins (genetics)</term><term>RNA-Binding Proteins (metabolism)</term><term>Stress, Physiological</term><term>Virus Replication</term><term>eIF-2 Kinase (genetics)</term><term>eIF-2 Kinase (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN double brin (génétique)</term><term>ARN double brin (métabolisme)</term><term>Activation enzymatique</term><term>Animaux</term><term>Antiviraux (métabolisme)</term><term>Expression des gènes</term><term>Facteurs nucléaires-90 (génétique)</term><term>Facteurs nucléaires-90 (métabolisme)</term><term>Granulations cytoplasmiques (métabolisme)</term><term>Humains</term><term>Interféron bêta (génétique)</term><term>Interféron bêta (métabolisme)</term><term>Liaison aux protéines</term><term>Modèles biologiques</term><term>Mutation</term><term>Phosphorylation</term><term>Protéines de liaison à l'ARN (génétique)</term><term>Protéines de liaison à l'ARN (métabolisme)</term><term>Réplication virale</term><term>Stress physiologique</term><term>Techniques de knock-down de gènes</term><term>Transport de protéines</term><term>Virus de la grippe A (génétique)</term><term>Virus de la grippe A (métabolisme)</term><term>eIF-2 Kinase (génétique)</term><term>eIF-2 Kinase (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interferon-beta</term><term>Nuclear Factor 90 Proteins</term><term>RNA, Double-Stranded</term><term>RNA-Binding Proteins</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiviral Agents</term><term>Interferon-beta</term><term>Nuclear Factor 90 Proteins</term><term>RNA, Double-Stranded</term><term>RNA-Binding Proteins</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN double brin</term><term>Facteurs nucléaires-90</term><term>Interféron bêta</term><term>Protéines de liaison à l'ARN</term><term>Virus de la grippe A</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cytoplasmic Granules</term><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN double brin</term><term>Antiviraux</term><term>Facteurs nucléaires-90</term><term>Granulations cytoplasmiques</term><term>Interféron bêta</term><term>Protéines de liaison à l'ARN</term><term>Virus de la grippe A</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Enzyme Activation</term><term>Gene Expression</term><term>Gene Knockdown Techniques</term><term>Humans</term><term>Models, Biological</term><term>Mutation</term><term>Phosphorylation</term><term>Protein Binding</term><term>Protein Transport</term><term>Stress, Physiological</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation enzymatique</term><term>Animaux</term><term>Expression des gènes</term><term>Humains</term><term>Liaison aux protéines</term><term>Modèles biologiques</term><term>Mutation</term><term>Phosphorylation</term><term>Réplication virale</term><term>Stress physiologique</term><term>Techniques de knock-down de gènes</term><term>Transport de protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">NF90 was shown to exhibit broad antiviral activity against several viruses, but detailed mechanisms remain unclear. In this study, we examined the molecular basis for the inhibitory effect of NF90 on virus replication mediated through protein kinase (PKR)-associated translational regulation. We first verified the interaction between NF90 and PKR in mammalian cells and showed that NF90 interacts with PKR through its C-terminal and that the interaction is independent of NF90 RNA-binding properties. We further showed that knockdown of NF90 resulted in significantly lower levels of PKR phosphorylation in response to dsRNA induction and influenza virus infection. We also showed that high concentrations of NF90 exhibit negative regulatory effects on PKR phosphorylation, presumably through competition for dsRNA via the C-terminal RNA-binding domain. PKR activation is essential for the formation of stress granules in response to dsRNA induction. Our results showed that NF90 is a component of stress granules. In NF90-knockdown cells, dsRNA treatment induced significantly lower levels of stress granules than in control cells. Further evidence for an NF90-PKR antiviral pathway was obtained using an NS1 mutated influenza A virus specifically attenuated in its ability to inhibit PKR activation. This mutant virus replicated indistinguishably from wild-type virus in NF90-knockdown cells, but not in scrambled control cells or Vero cells, indicating that NF90's antiviral function occurs through interaction with PKR. Taken together, these results reveal a yet-to-be defined host antiviral mechanism in which NF90 upregulation of PKR phosphorylation restricts virus infection. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><name sortKey="Chen, Yixin" sort="Chen, Yixin" uniqKey="Chen Y" first="Yixin" last="Chen">Yixin Chen</name><name sortKey="Huang, Xiaofeng" sort="Huang, Xiaofeng" uniqKey="Huang X" first="Xiaofeng" last="Huang">Xiaofeng Huang</name><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name><name sortKey="Lau, Siu Ying" sort="Lau, Siu Ying" uniqKey="Lau S" first="Siu-Ying" last="Lau">Siu-Ying Lau</name><name sortKey="Mok, Bobo Wing Yee" sort="Mok, Bobo Wing Yee" uniqKey="Mok B" first="Bobo Wing-Yee" last="Mok">Bobo Wing-Yee Mok</name><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Wen, Xi" sort="Wen, Xi" uniqKey="Wen X" first="Xi" last="Wen">Xi Wen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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