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The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity

The matrix (M) protein of wild isolates of rabies virus such as Tha (M-Tha) was previously shown to be able to interact with RelAp43, a protein of the NF-κB family, and to efficiently suppress NF-κB-dependent reporter gene expression, in contrast with the vaccine strain SAD. Here, we analyze the mec...

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Autores principales: Ben Khalifa, Youcef, Luco, Sophie, Besson, Benoit, Sonthonnax, Florian, Archambaud, Medhi, Grimes, Jonathan M., Larrous, Florence, Bourhy, Hervé
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175135/
https://www.ncbi.nlm.nih.gov/pubmed/28000711
http://dx.doi.org/10.1038/srep39420
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author Ben Khalifa, Youcef
Luco, Sophie
Besson, Benoit
Sonthonnax, Florian
Archambaud, Medhi
Grimes, Jonathan M.
Larrous, Florence
Bourhy, Hervé
author_facet Ben Khalifa, Youcef
Luco, Sophie
Besson, Benoit
Sonthonnax, Florian
Archambaud, Medhi
Grimes, Jonathan M.
Larrous, Florence
Bourhy, Hervé
author_sort Ben Khalifa, Youcef
collection PubMed
description The matrix (M) protein of wild isolates of rabies virus such as Tha (M-Tha) was previously shown to be able to interact with RelAp43, a protein of the NF-κB family, and to efficiently suppress NF-κB-dependent reporter gene expression, in contrast with the vaccine strain SAD. Here, we analyze the mechanisms involved in RelAp43-M protein interaction. We demonstrate that the central part of M-Tha, and the specific C-terminal region of RelAp43 are required for this interaction. Four differences in the corresponding amino acid sequences of the M-Tha and M-SAD are shown to be crucial for RelAp43 interaction and subsequent modulation of innate immune response. Furthermore, the capacity of M-Tha to interact with RelAp43 was shown to be crucial for the control of the expression of four genes (IFN, TNF, IL8 and CXCL2) during viral infection. These findings reveal that RelAp43 is a potent regulator of transcription of genes involved in innate immune response during rabies virus infection and that the M protein of wild isolates of rabies virus is a viral immune-modulatory factor playing an important role in this RelAp43-mediated host innate immunity response in contrast to M protein of vaccine strains, which have lost this property.
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spelling pubmed-51751352016-12-28 The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity Ben Khalifa, Youcef Luco, Sophie Besson, Benoit Sonthonnax, Florian Archambaud, Medhi Grimes, Jonathan M. Larrous, Florence Bourhy, Hervé Sci Rep Article The matrix (M) protein of wild isolates of rabies virus such as Tha (M-Tha) was previously shown to be able to interact with RelAp43, a protein of the NF-κB family, and to efficiently suppress NF-κB-dependent reporter gene expression, in contrast with the vaccine strain SAD. Here, we analyze the mechanisms involved in RelAp43-M protein interaction. We demonstrate that the central part of M-Tha, and the specific C-terminal region of RelAp43 are required for this interaction. Four differences in the corresponding amino acid sequences of the M-Tha and M-SAD are shown to be crucial for RelAp43 interaction and subsequent modulation of innate immune response. Furthermore, the capacity of M-Tha to interact with RelAp43 was shown to be crucial for the control of the expression of four genes (IFN, TNF, IL8 and CXCL2) during viral infection. These findings reveal that RelAp43 is a potent regulator of transcription of genes involved in innate immune response during rabies virus infection and that the M protein of wild isolates of rabies virus is a viral immune-modulatory factor playing an important role in this RelAp43-mediated host innate immunity response in contrast to M protein of vaccine strains, which have lost this property. Nature Publishing Group 2016-12-21 /pmc/articles/PMC5175135/ /pubmed/28000711 http://dx.doi.org/10.1038/srep39420 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ben Khalifa, Youcef
Luco, Sophie
Besson, Benoit
Sonthonnax, Florian
Archambaud, Medhi
Grimes, Jonathan M.
Larrous, Florence
Bourhy, Hervé
The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity
title The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity
title_full The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity
title_fullStr The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity
title_full_unstemmed The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity
title_short The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity
title_sort matrix protein of rabies virus binds to relap43 to modulate nf-κb-dependent gene expression related to innate immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175135/
https://www.ncbi.nlm.nih.gov/pubmed/28000711
http://dx.doi.org/10.1038/srep39420
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