Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production
The type I interferon (IFN) response is one of the primary defense systems against various pathogens. Although rubella virus (RuV) infection is known to cause dysfunction of various organs and systems, including the central nervous system, little is known about how human neural cells evoke protectiv...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/9799 |
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| author | Sayuri Sakuragi Huanan Liao Kodai Yajima Shigeyoshi Fujiwara Hiroyuki Nakamura |
| author_facet | Sayuri Sakuragi Huanan Liao Kodai Yajima Shigeyoshi Fujiwara Hiroyuki Nakamura |
| author_sort | Sayuri Sakuragi |
| collection | DOAJ |
| description | The type I interferon (IFN) response is one of the primary defense systems against various pathogens. Although rubella virus (RuV) infection is known to cause dysfunction of various organs and systems, including the central nervous system, little is known about how human neural cells evoke protective immunity against RuV infection, leading to controlling RuV replication. Using cultured human neural cells experimentally infected with RuV RA27/3 strain, we characterized the type I IFN immune response against the virus. RuV infected cultured human neural cell lines and induced IFN-β production, leading to the activation of signal transducer and activator of transcription 1 (STAT1) and the increased expression of IFN-stimulated genes (ISGs). Melanoma-differentiation-associated gene 5 (MDA5), one of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors, is required for the RuV-triggered IFN-β mRNA induction in U373MG cells. We also showed that upregulation of RuV-triggered ISGs was attenuated by blocking IFN-α/β receptor subunit 2 (IFNAR2) using an IFNAR2-specific neutralizing antibody or by repressing mitochondrial antiviral signaling protein (MAVS) expression using MAVS-targeting short hairpin RNA (shRNA). Furthermore, treating RuV-infected cells with BX-795, a TANK-binding kinase 1 (TBK1)/I kappa B kinase ε (IKKε) inhibitor, robustly reduced STAT1 phosphorylation and expression of ISGs, enhancing viral gene expression and infectious virion production. Overall, our findings suggest that the RuV-triggered type I IFN-mediated antiviral response is essential in controlling RuV gene expression and viral replication in human neural cells. |
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| language | English |
| last_indexed | 2024-03-10T01:45:25Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9d103420f6a6496d9e5f290d61bc5e842023-11-23T13:17:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317979910.3390/ijms23179799Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny ProductionSayuri Sakuragi0Huanan Liao1Kodai Yajima2Shigeyoshi Fujiwara3Hiroyuki Nakamura4Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDepartment of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDepartment of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDepartment of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDepartment of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanThe type I interferon (IFN) response is one of the primary defense systems against various pathogens. Although rubella virus (RuV) infection is known to cause dysfunction of various organs and systems, including the central nervous system, little is known about how human neural cells evoke protective immunity against RuV infection, leading to controlling RuV replication. Using cultured human neural cells experimentally infected with RuV RA27/3 strain, we characterized the type I IFN immune response against the virus. RuV infected cultured human neural cell lines and induced IFN-β production, leading to the activation of signal transducer and activator of transcription 1 (STAT1) and the increased expression of IFN-stimulated genes (ISGs). Melanoma-differentiation-associated gene 5 (MDA5), one of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors, is required for the RuV-triggered IFN-β mRNA induction in U373MG cells. We also showed that upregulation of RuV-triggered ISGs was attenuated by blocking IFN-α/β receptor subunit 2 (IFNAR2) using an IFNAR2-specific neutralizing antibody or by repressing mitochondrial antiviral signaling protein (MAVS) expression using MAVS-targeting short hairpin RNA (shRNA). Furthermore, treating RuV-infected cells with BX-795, a TANK-binding kinase 1 (TBK1)/I kappa B kinase ε (IKKε) inhibitor, robustly reduced STAT1 phosphorylation and expression of ISGs, enhancing viral gene expression and infectious virion production. Overall, our findings suggest that the RuV-triggered type I IFN-mediated antiviral response is essential in controlling RuV gene expression and viral replication in human neural cells.https://www.mdpi.com/1422-0067/23/17/9799rubella virusinnate immunityinterferon betatype I interferoninterferon-stimulated geneneural cell |
| spellingShingle | Sayuri Sakuragi Huanan Liao Kodai Yajima Shigeyoshi Fujiwara Hiroyuki Nakamura Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production International Journal of Molecular Sciences rubella virus innate immunity interferon beta type I interferon interferon-stimulated gene neural cell |
| title | Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production |
| title_full | Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production |
| title_fullStr | Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production |
| title_full_unstemmed | Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production |
| title_short | Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production |
| title_sort | rubella virus triggers type i interferon antiviral response in cultured human neural cells involvement in the control of viral gene expression and infectious progeny production |
| topic | rubella virus innate immunity interferon beta type I interferon interferon-stimulated gene neural cell |
| url | https://www.mdpi.com/1422-0067/23/17/9799 |
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