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

DOI: 10.1038/srep39420 DOI Help

Authors: Youcef Ben Khalifa (Institut Pasteur) , Sophie Luco (Institut Pasteur; Université Paris Diderot) , Benoit Besson (Institut Pasteur; Université Paris Diderot) , Florian Sonthonnax (Institut Pasteur; Université Paris Diderot) , Medhi Archambaud (Institut Pasteur; Université Paris Diderot) , Jonathan Grimes (Division of Structural Biology, University of Oxford; Diamond Light Source) , Florence Larrous (Institut Pasteur) , Hervé Bourhy (Institut Pasteur)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 6

State: Published (Approved)
Published: December 2016

Open Access Open Access

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.

Journal Keywords: Restriction factors; Viral infection

Subject Areas: Biology and Bio-materials, Medicine

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Added On: 10/01/2017 15:10


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