Flavivirus Capsid Proteins Inhibit the Interferon Response
Zika virus (ZIKV) establishes persistent infections in multiple human tissues, a phenomenon that likely plays a role in its ability to cause congenital birth defects and neurological disease. Multiple nonstructural proteins encoded by ZIKV, in particular NS5, are known to suppress the interferon (IF...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/5/968 |
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| author | Adriana M. Airo Alberto Felix-Lopez Valeria Mancinelli Danyel Evseev Joaquin Lopez-Orozco Kathy Shire Patrick Paszkowski Lori Frappier Katharine E. Magor Tom C. Hobman |
| author_facet | Adriana M. Airo Alberto Felix-Lopez Valeria Mancinelli Danyel Evseev Joaquin Lopez-Orozco Kathy Shire Patrick Paszkowski Lori Frappier Katharine E. Magor Tom C. Hobman |
| author_sort | Adriana M. Airo |
| collection | DOAJ |
| description | Zika virus (ZIKV) establishes persistent infections in multiple human tissues, a phenomenon that likely plays a role in its ability to cause congenital birth defects and neurological disease. Multiple nonstructural proteins encoded by ZIKV, in particular NS5, are known to suppress the interferon (IFN) response by attacking different steps in this critical antiviral pathway. Less well known are the potential roles of structural proteins in affecting the host immune response during ZIKV infection. Capsid proteins of flaviviruses are of particular interest because a pool of these viral proteins is targeted to the nuclei during infection and, as such, they have the potential to affect host cell gene expression. In this study, RNA-seq analyses revealed that capsid proteins from six different flaviviruses suppress expression of type I IFN and IFN-stimulated genes. Subsequent interactome and in vitro ubiquitination assays showed that ZIKV capsid protein binds to and prevents activating ubiquitination of RIG-I CARD domains by TRIM25, a host factor that is important for the induction arm of the IFN response. The other flavivirus capsid proteins also interacted with TRIM25, suggesting that these viral proteins may attenuate antiviral signaling pathways at very early stages of infection, potentially even before nonstructural proteins are produced. |
| first_indexed | 2024-03-10T01:37:55Z |
| format | Article |
| id | doaj.art-e9dd4fea08f24773acb3200a539d2344 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T01:37:55Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e9dd4fea08f24773acb3200a539d23442023-11-23T13:31:07ZengMDPI AGViruses1999-49152022-05-0114596810.3390/v14050968Flavivirus Capsid Proteins Inhibit the Interferon ResponseAdriana M. Airo0Alberto Felix-Lopez1Valeria Mancinelli2Danyel Evseev3Joaquin Lopez-Orozco4Kathy Shire5Patrick Paszkowski6Lori Frappier7Katharine E. Magor8Tom C. Hobman9Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, CanadaDepartment of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, CanadaHigh Content Analysis Core, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, CanadaDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, CanadaDepartment of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, CanadaDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, CanadaZika virus (ZIKV) establishes persistent infections in multiple human tissues, a phenomenon that likely plays a role in its ability to cause congenital birth defects and neurological disease. Multiple nonstructural proteins encoded by ZIKV, in particular NS5, are known to suppress the interferon (IFN) response by attacking different steps in this critical antiviral pathway. Less well known are the potential roles of structural proteins in affecting the host immune response during ZIKV infection. Capsid proteins of flaviviruses are of particular interest because a pool of these viral proteins is targeted to the nuclei during infection and, as such, they have the potential to affect host cell gene expression. In this study, RNA-seq analyses revealed that capsid proteins from six different flaviviruses suppress expression of type I IFN and IFN-stimulated genes. Subsequent interactome and in vitro ubiquitination assays showed that ZIKV capsid protein binds to and prevents activating ubiquitination of RIG-I CARD domains by TRIM25, a host factor that is important for the induction arm of the IFN response. The other flavivirus capsid proteins also interacted with TRIM25, suggesting that these viral proteins may attenuate antiviral signaling pathways at very early stages of infection, potentially even before nonstructural proteins are produced.https://www.mdpi.com/1999-4915/14/5/968flavivirusesglobal transcriptioncapsid proteininterferon responseTRIM25Zika virus |
| spellingShingle | Adriana M. Airo Alberto Felix-Lopez Valeria Mancinelli Danyel Evseev Joaquin Lopez-Orozco Kathy Shire Patrick Paszkowski Lori Frappier Katharine E. Magor Tom C. Hobman Flavivirus Capsid Proteins Inhibit the Interferon Response Viruses flaviviruses global transcription capsid protein interferon response TRIM25 Zika virus |
| title | Flavivirus Capsid Proteins Inhibit the Interferon Response |
| title_full | Flavivirus Capsid Proteins Inhibit the Interferon Response |
| title_fullStr | Flavivirus Capsid Proteins Inhibit the Interferon Response |
| title_full_unstemmed | Flavivirus Capsid Proteins Inhibit the Interferon Response |
| title_short | Flavivirus Capsid Proteins Inhibit the Interferon Response |
| title_sort | flavivirus capsid proteins inhibit the interferon response |
| topic | flaviviruses global transcription capsid protein interferon response TRIM25 Zika virus |
| url | https://www.mdpi.com/1999-4915/14/5/968 |
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