Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses
Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or Afric...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/9/1908 |
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| author | Fauziah Mohd Jaafar Mourad Belhouchet Baptiste Monsion Lesley Bell-Sakyi Peter P. C. Mertens Houssam Attoui |
| author_facet | Fauziah Mohd Jaafar Mourad Belhouchet Baptiste Monsion Lesley Bell-Sakyi Peter P. C. Mertens Houssam Attoui |
| author_sort | Fauziah Mohd Jaafar |
| collection | DOAJ |
| description | Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis. |
| first_indexed | 2024-03-10T21:51:31Z |
| format | Article |
| id | doaj.art-707490d10f164c6a93357643fd2b7fb1 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T21:51:31Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-707490d10f164c6a93357643fd2b7fb12023-11-19T13:23:25ZengMDPI AGViruses1999-49152023-09-01159190810.3390/v15091908Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular ResponsesFauziah Mohd Jaafar0Mourad Belhouchet1Baptiste Monsion2Lesley Bell-Sakyi3Peter P. C. Mertens4Houssam Attoui5UMR1161 VIROLOGIE, INRAE, Ecole Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, FranceDivision of Structural Biology, Henry Wellcome Building for Genomic Medicine, Oxford OX3 7BN, UKUMR1161 VIROLOGIE, INRAE, Ecole Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, FranceDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, 146 Brownlow Hill, Liverpool L3 5RF, UKOne Virology, The Wolfson Centre for Global Virus Research, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UKUMR1161 VIROLOGIE, INRAE, Ecole Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, FranceNon-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.https://www.mdpi.com/1999-4915/15/9/1908orbivirusbluetongue virusGreat Island virusSt. Croix River virusNS4innate responses |
| spellingShingle | Fauziah Mohd Jaafar Mourad Belhouchet Baptiste Monsion Lesley Bell-Sakyi Peter P. C. Mertens Houssam Attoui Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses Viruses orbivirus bluetongue virus Great Island virus St. Croix River virus NS4 innate responses |
| title | Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses |
| title_full | Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses |
| title_fullStr | Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses |
| title_full_unstemmed | Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses |
| title_short | Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses |
| title_sort | orbivirus ns4 proteins play multiple roles to dampen cellular responses |
| topic | orbivirus bluetongue virus Great Island virus St. Croix River virus NS4 innate responses |
| url | https://www.mdpi.com/1999-4915/15/9/1908 |
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