title: The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity.
abstract: 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.
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.
authors.forename: Youcef
authors.initials: Y
authors.lastname: Ben Khalifa
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, rue du docteur Roux, 75015 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Luco
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, rue du docteur Roux, 75015 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Besson
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, rue du docteur Roux, 75015 Paris, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Sonthonnax
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, rue du docteur Roux, 75015 Paris, France.
authors.forename: Medhi
authors.initials: M
authors.lastname: Archambaud
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|Diamond Light Source Limited, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grimes
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Larrous
authors.affiliation: Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, 25 rue du docteur Roux, 75015 Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bourhy
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000276:immunology*; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D011818:Rabies / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D011820:Rabies virus / Q000276:immunology* / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014764:Viral Proteins