Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein
Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression...
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MDPI AG
2021-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/9/2399 |
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| author | Ermela Paparisto Nina R. Hunt Daniel S. Labach Macon D. Coleman Eric J. Di Gravio Mackenzie J. Dodge Nicole J. Friesen Marceline Côté Andreas Müller Thomas Hoenen Stephen D. Barr |
| author_facet | Ermela Paparisto Nina R. Hunt Daniel S. Labach Macon D. Coleman Eric J. Di Gravio Mackenzie J. Dodge Nicole J. Friesen Marceline Côté Andreas Müller Thomas Hoenen Stephen D. Barr |
| author_sort | Ermela Paparisto |
| collection | DOAJ |
| description | Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identify a novel ‘protagonist–antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics. |
| first_indexed | 2024-03-10T07:49:04Z |
| format | Article |
| id | doaj.art-297711648a4f49ebb60f09d6ccd3db49 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:49:04Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-297711648a4f49ebb60f09d6ccd3db492023-11-22T12:25:33ZengMDPI AGCells2073-44092021-09-01109239910.3390/cells10092399Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola GlycoproteinErmela Paparisto0Nina R. Hunt1Daniel S. Labach2Macon D. Coleman3Eric J. Di Gravio4Mackenzie J. Dodge5Nicole J. Friesen6Marceline Côté7Andreas Müller8Thomas Hoenen9Stephen D. Barr10Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaDepartment of Biochemistry, Microbiology, and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Roger-Guindon Hall Room 4214, Ottawa, ON K1H 8M5 , CanadaFriedrich-Loeffler-Institut, Institute of Molecular Virology and Cell Biology, Südufer 10, 17493 Greifswald—Insel Riems, GermanyFriedrich-Loeffler-Institut, Institute of Molecular Virology and Cell Biology, Südufer 10, 17493 Greifswald—Insel Riems, GermanyDepartment of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, CanadaSurvival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identify a novel ‘protagonist–antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.https://www.mdpi.com/2073-4409/10/9/2399Ebola virusMarburg virusHERC5antiviralinterferon |
| spellingShingle | Ermela Paparisto Nina R. Hunt Daniel S. Labach Macon D. Coleman Eric J. Di Gravio Mackenzie J. Dodge Nicole J. Friesen Marceline Côté Andreas Müller Thomas Hoenen Stephen D. Barr Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein Cells Ebola virus Marburg virus HERC5 antiviral interferon |
| title | Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein |
| title_full | Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein |
| title_fullStr | Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein |
| title_full_unstemmed | Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein |
| title_short | Interferon-Induced HERC5 Inhibits Ebola Virus Particle Production and Is Antagonized by Ebola Glycoprotein |
| title_sort | interferon induced herc5 inhibits ebola virus particle production and is antagonized by ebola glycoprotein |
| topic | Ebola virus Marburg virus HERC5 antiviral interferon |
| url | https://www.mdpi.com/2073-4409/10/9/2399 |
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