Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling
Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate...
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MDPI AG
2021-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/1/140 |
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| author | Giulia Gallo Grégory Caignard Karine Badonnel Guillaume Chevreux Samuel Terrier Agnieszka Szemiel Gleyder Roman-Sosa Florian Binder Quan Gu Ana Da Silva Filipe Rainer G. Ulrich Alain Kohl Damien Vitour Noël Tordo Myriam Ermonval |
| author_facet | Giulia Gallo Grégory Caignard Karine Badonnel Guillaume Chevreux Samuel Terrier Agnieszka Szemiel Gleyder Roman-Sosa Florian Binder Quan Gu Ana Da Silva Filipe Rainer G. Ulrich Alain Kohl Damien Vitour Noël Tordo Myriam Ermonval |
| author_sort | Giulia Gallo |
| collection | DOAJ |
| description | Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate in infected cells. We studied interactions of structural and nonstructural (NSs) proteins of pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), and non-pathogenic Prospect Hill (PHV) viruses, with human type I and III IFN (IFN-I and IFN-III) pathways. The NSs proteins of all three viruses inhibited the RIG-I-activated IFNβ promoter, while only the glycoprotein precursor (GPC) of PUUV, or its cleavage product Gn/Gc, and the nucleocapsid (N) of TULV inhibited it. Moreover, the GPC of both PUUV and TULV antagonized the promoter of IFN-stimulated responsive elements (ISRE). Different viral proteins could thus contribute to inhibition of IFNβ response in a viral context. While PUUV and TULV strains replicated similarly, whether expressing entire or truncated NSs proteins, only PUUV encoding a wild type NSs protein led to late IFN expression and activation of IFN-stimulated genes (ISG). This, together with the identification of particular domains of NSs proteins and different biological processes that are associated with cellular proteins in complex with NSs proteins, suggested that the activation of IFN-I is probably not the only antiviral pathway to be counteracted by orthohantaviruses and that NSs proteins could have multiple inhibitory functions. |
| first_indexed | 2024-03-09T04:17:16Z |
| format | Article |
| id | doaj.art-a80738632ee44cc5bacfc3f5bc7cdb08 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T04:17:16Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a80738632ee44cc5bacfc3f5bc7cdb082023-12-03T13:52:45ZengMDPI AGViruses1999-49152021-01-0113114010.3390/v13010140Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon SignalingGiulia Gallo0Grégory Caignard1Karine Badonnel2Guillaume Chevreux3Samuel Terrier4Agnieszka Szemiel5Gleyder Roman-Sosa6Florian Binder7Quan Gu8Ana Da Silva Filipe9Rainer G. Ulrich10Alain Kohl11Damien Vitour12Noël Tordo13Myriam Ermonval14Unité des Stratégies Antivirales, Institut Pasteur, 75015 Paris, FranceUMR 1161 Virologie, Anses-INRAE-EnvA, 94700 Maisons-Alfort, FranceBREED, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceInstitut Jacques Monod, CNRS UMR 7592, ProteoSeine Mass Spectrometry Plateform, Université de Paris, 75013 Paris, FranceInstitut Jacques Monod, CNRS UMR 7592, ProteoSeine Mass Spectrometry Plateform, Université de Paris, 75013 Paris, FranceMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKUnité de Biologie Structurale, Institut Pasteur, 75015 Paris, FranceFriedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, 17493 Greifswald-Insel Riems, GermanyMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKFriedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, 17493 Greifswald-Insel Riems, GermanyMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UKUMR 1161 Virologie, Anses-INRAE-EnvA, 94700 Maisons-Alfort, FranceUnité des Stratégies Antivirales, Institut Pasteur, 75015 Paris, FranceUnité des Stratégies Antivirales, Institut Pasteur, 75015 Paris, FranceRodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate in infected cells. We studied interactions of structural and nonstructural (NSs) proteins of pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), and non-pathogenic Prospect Hill (PHV) viruses, with human type I and III IFN (IFN-I and IFN-III) pathways. The NSs proteins of all three viruses inhibited the RIG-I-activated IFNβ promoter, while only the glycoprotein precursor (GPC) of PUUV, or its cleavage product Gn/Gc, and the nucleocapsid (N) of TULV inhibited it. Moreover, the GPC of both PUUV and TULV antagonized the promoter of IFN-stimulated responsive elements (ISRE). Different viral proteins could thus contribute to inhibition of IFNβ response in a viral context. While PUUV and TULV strains replicated similarly, whether expressing entire or truncated NSs proteins, only PUUV encoding a wild type NSs protein led to late IFN expression and activation of IFN-stimulated genes (ISG). This, together with the identification of particular domains of NSs proteins and different biological processes that are associated with cellular proteins in complex with NSs proteins, suggested that the activation of IFN-I is probably not the only antiviral pathway to be counteracted by orthohantaviruses and that NSs proteins could have multiple inhibitory functions.https://www.mdpi.com/1999-4915/13/1/140orthohantavirusinterferon responsenonstructural proteinglycoproteinPuumala virusTula virus |
| spellingShingle | Giulia Gallo Grégory Caignard Karine Badonnel Guillaume Chevreux Samuel Terrier Agnieszka Szemiel Gleyder Roman-Sosa Florian Binder Quan Gu Ana Da Silva Filipe Rainer G. Ulrich Alain Kohl Damien Vitour Noël Tordo Myriam Ermonval Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling Viruses orthohantavirus interferon response nonstructural protein glycoprotein Puumala virus Tula virus |
| title | Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling |
| title_full | Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling |
| title_fullStr | Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling |
| title_full_unstemmed | Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling |
| title_short | Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling |
| title_sort | interactions of viral proteins from pathogenic and low or non pathogenic orthohantaviruses with human type i interferon signaling |
| topic | orthohantavirus interferon response nonstructural protein glycoprotein Puumala virus Tula virus |
| url | https://www.mdpi.com/1999-4915/13/1/140 |
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