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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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Autores principales: Gallo, Giulia, Caignard, Grégory, Badonnel, Karine, Chevreux, Guillaume, Terrier, Samuel, Szemiel, Agnieszka, Roman-Sosa, Gleyder, Binder, Florian, Gu, Quan, Da Silva Filipe, Ana, Ulrich, Rainer G., Kohl, Alain, Vitour, Damien, Tordo, Noël, Ermonval, Myriam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835746/
https://www.ncbi.nlm.nih.gov/pubmed/33478127
http://dx.doi.org/10.3390/v13010140
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author Gallo, Giulia
Caignard, Grégory
Badonnel, Karine
Chevreux, Guillaume
Terrier, Samuel
Szemiel, Agnieszka
Roman-Sosa, Gleyder
Binder, Florian
Gu, Quan
Da Silva Filipe, Ana
Ulrich, Rainer G.
Kohl, Alain
Vitour, Damien
Tordo, Noël
Ermonval, Myriam
author_facet Gallo, Giulia
Caignard, Grégory
Badonnel, Karine
Chevreux, Guillaume
Terrier, Samuel
Szemiel, Agnieszka
Roman-Sosa, Gleyder
Binder, Florian
Gu, Quan
Da Silva Filipe, Ana
Ulrich, Rainer G.
Kohl, Alain
Vitour, Damien
Tordo, Noël
Ermonval, Myriam
author_sort Gallo, Giulia
collection PubMed
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.
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spelling pubmed-78357462021-01-27 Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling Gallo, Giulia Caignard, Grégory Badonnel, Karine Chevreux, Guillaume Terrier, Samuel Szemiel, Agnieszka Roman-Sosa, Gleyder Binder, Florian Gu, Quan Da Silva Filipe, Ana Ulrich, Rainer G. Kohl, Alain Vitour, Damien Tordo, Noël Ermonval, Myriam Viruses Article 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. MDPI 2021-01-19 /pmc/articles/PMC7835746/ /pubmed/33478127 http://dx.doi.org/10.3390/v13010140 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gallo, Giulia
Caignard, Grégory
Badonnel, Karine
Chevreux, Guillaume
Terrier, Samuel
Szemiel, Agnieszka
Roman-Sosa, Gleyder
Binder, Florian
Gu, Quan
Da Silva Filipe, Ana
Ulrich, Rainer G.
Kohl, Alain
Vitour, Damien
Tordo, Noël
Ermonval, Myriam
Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835746/
https://www.ncbi.nlm.nih.gov/pubmed/33478127
http://dx.doi.org/10.3390/v13010140
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