Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfac...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/4/589 |
| _version_ | 1797539376189669376 |
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| author | Gennaro Iaconis Ben Jackson Kay Childs Mark Boyce Stephen Goodbourn Neil Blake Miren Iturriza-Gomara Julian Seago |
| author_facet | Gennaro Iaconis Ben Jackson Kay Childs Mark Boyce Stephen Goodbourn Neil Blake Miren Iturriza-Gomara Julian Seago |
| author_sort | Gennaro Iaconis |
| collection | DOAJ |
| description | Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfaces due to restricted expression of the type III IFN receptor. Rotavirus (RV) replicates in intestinal epithelial cells that respond predominantly to type III IFNs, and it has been shown that type III rather than type I IFNs are important for controlling RV infections in vivo. The RV NSP1 protein antagonizes the host type I IFN response by targeting IRF-3, IRF-5, IRF-7, or β-TrCP for proteasome-mediated degradation in a strain-specific manner. Here we provide the first demonstration that NSP1 proteins from several human and animal RV strains antagonize type III as well as type I IFN induction. We also show that NSP1 is a potent inhibitor of IRF-1, a previously undescribed property of NSP1 which is conserved among human and animal RVs. Interestingly, all NSP1 proteins were substantially more effective inhibitors of IRF-1 than either IRF-3 or IRF-7 which has significance for evasion of basal anti-viral immunity and type III IFN induction in the intestinal epithelium. |
| first_indexed | 2024-03-10T12:45:09Z |
| format | Article |
| id | doaj.art-0d3d956a29a94d628db73ae658cede98 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T12:45:09Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0d3d956a29a94d628db73ae658cede982023-11-21T13:31:39ZengMDPI AGViruses1999-49152021-03-0113458910.3390/v13040589Rotavirus NSP1 Inhibits Type I and Type III Interferon InductionGennaro Iaconis0Ben Jackson1Kay Childs2Mark Boyce3Stephen Goodbourn4Neil Blake5Miren Iturriza-Gomara6Julian Seago7The Pirbright Institute, Ash Road, Woking, Surrey GU24 0NF, UKThe Pirbright Institute, Ash Road, Woking, Surrey GU24 0NF, UKThe Pirbright Institute, Ash Road, Woking, Surrey GU24 0NF, UKDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UKInstitute for Infection and Immunity, St. George’s, University of London, London SW17 0RE, UKInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UKInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UKThe Pirbright Institute, Ash Road, Woking, Surrey GU24 0NF, UKType I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfaces due to restricted expression of the type III IFN receptor. Rotavirus (RV) replicates in intestinal epithelial cells that respond predominantly to type III IFNs, and it has been shown that type III rather than type I IFNs are important for controlling RV infections in vivo. The RV NSP1 protein antagonizes the host type I IFN response by targeting IRF-3, IRF-5, IRF-7, or β-TrCP for proteasome-mediated degradation in a strain-specific manner. Here we provide the first demonstration that NSP1 proteins from several human and animal RV strains antagonize type III as well as type I IFN induction. We also show that NSP1 is a potent inhibitor of IRF-1, a previously undescribed property of NSP1 which is conserved among human and animal RVs. Interestingly, all NSP1 proteins were substantially more effective inhibitors of IRF-1 than either IRF-3 or IRF-7 which has significance for evasion of basal anti-viral immunity and type III IFN induction in the intestinal epithelium.https://www.mdpi.com/1999-4915/13/4/589rotavirustype I interferontype III interferonNSP1IRF-1IRF-3 |
| spellingShingle | Gennaro Iaconis Ben Jackson Kay Childs Mark Boyce Stephen Goodbourn Neil Blake Miren Iturriza-Gomara Julian Seago Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction Viruses rotavirus type I interferon type III interferon NSP1 IRF-1 IRF-3 |
| title | Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction |
| title_full | Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction |
| title_fullStr | Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction |
| title_full_unstemmed | Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction |
| title_short | Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction |
| title_sort | rotavirus nsp1 inhibits type i and type iii interferon induction |
| topic | rotavirus type I interferon type III interferon NSP1 IRF-1 IRF-3 |
| url | https://www.mdpi.com/1999-4915/13/4/589 |
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