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A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells

Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the t...

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Autores principales: Le May, Nicolas, Mansuroglu, Zeyni, Léger, Psylvia, Josse, Thibaut, Blot, Guillaume, Billecocq, Agnès, Flick, Ramon, Jacob, Yves, Bonnefoy, Eliette, Bouloy, Michèle
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323286/
https://www.ncbi.nlm.nih.gov/pubmed/18225953
http://dx.doi.org/10.1371/journal.ppat.0040013
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author Le May, Nicolas
Mansuroglu, Zeyni
Léger, Psylvia
Josse, Thibaut
Blot, Guillaume
Billecocq, Agnès
Flick, Ramon
Jacob, Yves
Bonnefoy, Eliette
Bouloy, Michèle
author_facet Le May, Nicolas
Mansuroglu, Zeyni
Léger, Psylvia
Josse, Thibaut
Blot, Guillaume
Billecocq, Agnès
Flick, Ramon
Jacob, Yves
Bonnefoy, Eliette
Bouloy, Michèle
author_sort Le May, Nicolas
collection PubMed
description Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the transcription factor YY1 that regulates IFN-β gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated factors are recruited on the IFN-β promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-β promoter chromatin structure.
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spelling pubmed-23232862008-04-18 A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells Le May, Nicolas Mansuroglu, Zeyni Léger, Psylvia Josse, Thibaut Blot, Guillaume Billecocq, Agnès Flick, Ramon Jacob, Yves Bonnefoy, Eliette Bouloy, Michèle PLoS Pathog Research Article Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the transcription factor YY1 that regulates IFN-β gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated factors are recruited on the IFN-β promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-β promoter chromatin structure. Public Library of Science 2008-01 2008-01-25 /pmc/articles/PMC2323286/ /pubmed/18225953 http://dx.doi.org/10.1371/journal.ppat.0040013 Text en © 2008 Le May et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Le May, Nicolas
Mansuroglu, Zeyni
Léger, Psylvia
Josse, Thibaut
Blot, Guillaume
Billecocq, Agnès
Flick, Ramon
Jacob, Yves
Bonnefoy, Eliette
Bouloy, Michèle
A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells
title A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells
title_full A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells
title_fullStr A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells
title_full_unstemmed A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells
title_short A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells
title_sort sap30 complex inhibits ifn-β expression in rift valley fever virus infected cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323286/
https://www.ncbi.nlm.nih.gov/pubmed/18225953
http://dx.doi.org/10.1371/journal.ppat.0040013
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