DDX3 Interacts with Influenza A Virus NS1 and NP Proteins and Exerts Antiviral Function through Regulation of Stress Granule Formation.
Identifieur interne : 000B89 ( Main/Exploration ); précédent : 000B88; suivant : 000B90DDX3 Interacts with Influenza A Virus NS1 and NP Proteins and Exerts Antiviral Function through Regulation of Stress Granule Formation.
Auteurs : Sathya N. Thulasi Raman [Canada] ; Guanqun Liu [Canada] ; Hyun Mi Pyo [Canada] ; Ya Cheng Cui [Canada] ; Fang Xu [Canada] ; Lisanework E. Ayalew [Canada] ; Suresh K. Tikoo [Canada] ; Yan Zhou [Canada]Source :
- Journal of virology [ 1098-5514 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Cartographie d'interactions entre protéines, Cellules cultivées, Cellules épithéliales (immunologie), Cellules épithéliales (virologie), Charge virale, DEAD-box RNA helicases (métabolisme), Immunoprécipitation, Interactions hôte-pathogène, Liaison aux protéines, Protéines de liaison à l'ARN (métabolisme), Protéines du core viral (métabolisme), Protéines virales non structurales (métabolisme), Sous-type H1N1 du virus de la grippe A (croissance et développement), Sous-type H1N1 du virus de la grippe A (immunologie).
- MESH :
- croissance et développement : Sous-type H1N1 du virus de la grippe A.
- immunologie : Cellules épithéliales, Sous-type H1N1 du virus de la grippe A.
- métabolisme : DEAD-box RNA helicases, Protéines de liaison à l'ARN, Protéines du core viral, Protéines virales non structurales.
- virologie : Cellules épithéliales.
- Animaux, Cartographie d'interactions entre protéines, Cellules cultivées, Charge virale, Immunoprécipitation, Interactions hôte-pathogène, Liaison aux protéines.
English descriptors
- KwdEn :
- Animals, Cells, Cultured, DEAD-box RNA Helicases (metabolism), Epithelial Cells (immunology), Epithelial Cells (virology), Host-Pathogen Interactions, Immunoprecipitation, Influenza A Virus, H1N1 Subtype (growth & development), Influenza A Virus, H1N1 Subtype (immunology), Protein Binding, Protein Interaction Mapping, RNA-Binding Proteins (metabolism), Viral Core Proteins (metabolism), Viral Load, Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , metabolism : DEAD-box RNA Helicases, RNA-Binding Proteins, Viral Core Proteins, Viral Nonstructural Proteins.
- growth & development : Influenza A Virus, H1N1 Subtype.
- immunology : Epithelial Cells, Influenza A Virus, H1N1 Subtype.
- virology : Epithelial Cells.
- Animals, Cells, Cultured, Host-Pathogen Interactions, Immunoprecipitation, Protein Binding, Protein Interaction Mapping, Viral Load.
Abstract
DDX3 belongs to the DEAD box RNA helicase family and is a multifunctional protein affecting the life cycle of a variety of viruses. However, its role in influenza virus infection is unknown. In this study, we explored the potential role of DDX3 in influenza virus life cycle and discovered that DDX3 is an antiviral protein. Since many host proteins affect virus life cycle by interacting with certain components of the viral machinery, we first verified whether DDX3 has any viral interaction partners. Immunoprecipitation studies revealed NS1 and NP as direct interaction partners of DDX3. Stress granules (SGs) are known to be antiviral and do form in influenza virus-infected cells expressing defective NS1 protein. Additionally, a recent study showed that DDX3 is an important SG-nucleating factor. We thus explored whether DDX3 plays a role in influenza virus infection through regulation of SGs. Our results showed that SGs were formed in infected cells upon infection with a mutant influenza virus lacking functional NS1 (del NS1) protein, and DDX3 colocalized with NP in SGs. We further determined that the DDX3 helicase domain did not interact with NS1 and NP; however, it was essential for DDX3 localization in virus-induced SGs. Knockdown of DDX3 resulted in impaired SG formation and led to increased virus titers. Taken together, our results identified DDX3 as an antiviral protein with a role in virus-induced SG formation.
DOI: 10.1128/JVI.03010-15
PubMed: 26792746
Affiliations:
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Le document en format XML
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Tikoo</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Yan" sort="Zhou, Yan" uniqKey="Zhou Y" first="Yan" last="Zhou">Yan Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada yan.zhou@usask.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26792746</idno><idno type="pmid">26792746</idno><idno type="doi">10.1128/JVI.03010-15</idno><idno type="wicri:Area/PubMed/Corpus">000379</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000379</idno><idno type="wicri:Area/PubMed/Curation">000378</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000378</idno><idno type="wicri:Area/PubMed/Checkpoint">000375</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000375</idno><idno type="wicri:Area/Ncbi/Merge">000771</idno><idno type="wicri:Area/Ncbi/Curation">000771</idno><idno type="wicri:Area/Ncbi/Checkpoint">000771</idno><idno type="wicri:Area/Main/Merge">000B89</idno><idno type="wicri:Area/Main/Curation">000B89</idno><idno type="wicri:Area/Main/Exploration">000B89</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">DDX3 Interacts with Influenza A Virus NS1 and NP Proteins and Exerts Antiviral Function through Regulation of Stress Granule Formation.</title><author><name sortKey="Thulasi Raman, Sathya N" sort="Thulasi Raman, Sathya N" uniqKey="Thulasi Raman S" first="Sathya N" last="Thulasi Raman">Sathya N. Thulasi Raman</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Guanqun" sort="Liu, Guanqun" uniqKey="Liu G" first="Guanqun" last="Liu">Guanqun Liu</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Pyo, Hyun Mi" sort="Pyo, Hyun Mi" uniqKey="Pyo H" first="Hyun Mi" last="Pyo">Hyun Mi Pyo</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Cui, Ya Cheng" sort="Cui, Ya Cheng" uniqKey="Cui Y" first="Ya Cheng" last="Cui">Ya Cheng Cui</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Fang" sort="Xu, Fang" uniqKey="Xu F" first="Fang" last="Xu">Fang Xu</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Ayalew, Lisanework E" sort="Ayalew, Lisanework E" uniqKey="Ayalew L" first="Lisanework E" last="Ayalew">Lisanework E. Ayalew</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Tikoo, Suresh K" sort="Tikoo, Suresh K" uniqKey="Tikoo S" first="Suresh K" last="Tikoo">Suresh K. Tikoo</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Yan" sort="Zhou, Yan" uniqKey="Zhou Y" first="Yan" last="Zhou">Yan Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada yan.zhou@usask.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Vaccinology & Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan</wicri:regionArea><wicri:noRegion>Saskatchewan</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>DEAD-box RNA Helicases (metabolism)</term><term>Epithelial Cells (immunology)</term><term>Epithelial Cells (virology)</term><term>Host-Pathogen Interactions</term><term>Immunoprecipitation</term><term>Influenza A Virus, H1N1 Subtype (growth & development)</term><term>Influenza A Virus, H1N1 Subtype (immunology)</term><term>Protein Binding</term><term>Protein Interaction Mapping</term><term>RNA-Binding Proteins (metabolism)</term><term>Viral Core Proteins (metabolism)</term><term>Viral Load</term><term>Viral Nonstructural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cartographie d'interactions entre protéines</term><term>Cellules cultivées</term><term>Cellules épithéliales (immunologie)</term><term>Cellules épithéliales (virologie)</term><term>Charge virale</term><term>DEAD-box RNA helicases (métabolisme)</term><term>Immunoprécipitation</term><term>Interactions hôte-pathogène</term><term>Liaison aux protéines</term><term>Protéines de liaison à l'ARN (métabolisme)</term><term>Protéines du core viral (métabolisme)</term><term>Protéines virales non structurales (métabolisme)</term><term>Sous-type H1N1 du virus de la grippe A (croissance et développement)</term><term>Sous-type H1N1 du virus de la grippe A (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DEAD-box RNA Helicases</term><term>RNA-Binding Proteins</term><term>Viral Core Proteins</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules épithéliales</term><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Epithelial Cells</term><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>DEAD-box RNA helicases</term><term>Protéines de liaison à l'ARN</term><term>Protéines du core viral</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules épithéliales</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Epithelial Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Host-Pathogen Interactions</term><term>Immunoprecipitation</term><term>Protein Binding</term><term>Protein Interaction Mapping</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie d'interactions entre protéines</term><term>Cellules cultivées</term><term>Charge virale</term><term>Immunoprécipitation</term><term>Interactions hôte-pathogène</term><term>Liaison aux protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">DDX3 belongs to the DEAD box RNA helicase family and is a multifunctional protein affecting the life cycle of a variety of viruses. However, its role in influenza virus infection is unknown. In this study, we explored the potential role of DDX3 in influenza virus life cycle and discovered that DDX3 is an antiviral protein. Since many host proteins affect virus life cycle by interacting with certain components of the viral machinery, we first verified whether DDX3 has any viral interaction partners. Immunoprecipitation studies revealed NS1 and NP as direct interaction partners of DDX3. Stress granules (SGs) are known to be antiviral and do form in influenza virus-infected cells expressing defective NS1 protein. Additionally, a recent study showed that DDX3 is an important SG-nucleating factor. We thus explored whether DDX3 plays a role in influenza virus infection through regulation of SGs. Our results showed that SGs were formed in infected cells upon infection with a mutant influenza virus lacking functional NS1 (del NS1) protein, and DDX3 colocalized with NP in SGs. We further determined that the DDX3 helicase domain did not interact with NS1 and NP; however, it was essential for DDX3 localization in virus-induced SGs. Knockdown of DDX3 resulted in impaired SG formation and led to increased virus titers. Taken together, our results identified DDX3 as an antiviral protein with a role in virus-induced SG formation.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Thulasi Raman, Sathya N" sort="Thulasi Raman, Sathya N" uniqKey="Thulasi Raman S" first="Sathya N" last="Thulasi Raman">Sathya N. Thulasi Raman</name></noRegion><name sortKey="Ayalew, Lisanework E" sort="Ayalew, Lisanework E" uniqKey="Ayalew L" first="Lisanework E" last="Ayalew">Lisanework E. Ayalew</name><name sortKey="Cui, Ya Cheng" sort="Cui, Ya Cheng" uniqKey="Cui Y" first="Ya Cheng" last="Cui">Ya Cheng Cui</name><name sortKey="Liu, Guanqun" sort="Liu, Guanqun" uniqKey="Liu G" first="Guanqun" last="Liu">Guanqun Liu</name><name sortKey="Pyo, Hyun Mi" sort="Pyo, Hyun Mi" uniqKey="Pyo H" first="Hyun Mi" last="Pyo">Hyun Mi Pyo</name><name sortKey="Tikoo, Suresh K" sort="Tikoo, Suresh K" uniqKey="Tikoo S" first="Suresh K" last="Tikoo">Suresh K. Tikoo</name><name sortKey="Xu, Fang" sort="Xu, Fang" uniqKey="Xu F" first="Fang" last="Xu">Fang Xu</name><name sortKey="Zhou, Yan" sort="Zhou, Yan" uniqKey="Zhou Y" first="Yan" last="Zhou">Yan Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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