About: Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway

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About: Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway
Creator	Vitour, Damien Breard, Emmanuel Fablet, Aurore Gorlier, Axel Kundlacz, Cindy Lecollinet, Sylvie Léger, Thibaut Morlet, Bastien Pourcelot, Marie Sailleau, Corinne Viarouge, Cyril Silva, Da Van Rijn, Piet Amaral, Rayane Caignard, Moraes,
source	BioRxiv; MedRxiv
abstract	Bluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide range of wild and domestic ruminants. In this report, we showed that BTV, through its virulence non-structural protein NS3 (BTV-NS3), is able to activate the MAPK/ERK pathway. In response to growth factors, the MAPK/ERK pathway activates cell survival, differentiation, proliferation and protein translation but can also lead to the production of several inflammatory cytokines. By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein kinase B-Raf (BRAF), a crucial player of the MAPK/ERK pathway, as a new cellular interactor of BTV-NS3. BRAF silencing led to a significant decrease of the MAPK/ERK activation by BTV supporting a model where BTV-NS3 interacts with BRAF to activate this signaling cascade. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be specific to BTV compared to other members of Orbivirus genus. Inhibition of MAPK/ERK pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its own replication. Therefore, the activation of the MAPK/ERK pathway by BTV-NS3 could benefit to BTV replication by promoting its own viral protein synthesis but could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease. Altogether, our data provide molecular mechanisms to explain the role of BTV-NS3 as a virulence factor and determinant of pathogenesis. Bluetongue Virus (BTV) is responsible of the non-contagious arthropod-borne disease Bluetongue (BT) transmitted to ruminants by blood-feeding midges. Despite the fact that BTV has been extensively studied, we still have little understanding of the molecular determinants of BTV virulence. In this report, we found that the virulence protein NS3 interacts with BRAF, a key component of the MAPK/ERK pathway. In response to growth factors, this pathway promotes cell survival, increases protein translation but also contributes to the production of inflammatory cytokines. We showed that BTV-NS3 enhances the MAPK/ERK pathway and this activation is BRAF-dependent. Our results demonstrate, at the molecular level, how a single virulence factor has evolved to target a cellular function to ensure its viral replication. On the other hand, our findings could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease.
has issue date	2019-02-27(xsd:dateTime)
bibo:doi	10.1101/562421
has license	medrxiv
sha1sum (hex)	17db8a23e909067a6460e469c0da483047c4f2cb
schema:url	https://doi.org/10.1101/562421
resource representing a document's title	Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway
schema:publication	bioRxiv
resource representing a document's body	covid:17db8a23e909067a6460e469c0da483047c4f2cb#body_text
is schema:about of	named entity 'virulence factor' named entity 'BTV' named entity 'activation' named entity 'specific' named entity 'multiple' named entity 'determinants' named entity 'activate' named entity 'MAPK/ERK pathway' named entity 'midges' named entity 'lead' named entity 'activate' named entity 'blood-feeding' named entity 'BRAF' named entity 'NS3' named entity 'Bluetongue' named entity 'Despite' named entity 'Bluetongue virus' named entity 'ruminants' named entity 'inflammation' named entity 'cascade' named entity 'transfected' named entity 'blood-feeding' named entity 'observed' named entity 'conserved' named entity 'disease' named entity 'transmitted' named entity 'BRAF' named entity 'ruminants' named entity 'provide' named entity 'BRAF' named entity 'non-contagious' named entity 'fact' named entity 'cases' named entity 'survival' named entity 'serine/threonine' named entity 'virulence protein' named entity 'transfected' named entity 'MAPK' named entity 'arbovirus' named entity 'arthropod-borne' named entity 'Bluetongue' named entity 'BRAF' named entity 'virulence factor' named entity 'ruminants' named entity 'pathogenesis' named entity 'ERK pathway' named entity 'NS3' named entity 'kidney' named entity 'STAT1' named entity 'vascular permeability' named entity 'EGF' named entity 'confocal microscopy' named entity 'eIF4E' named entity '293T cells' named entity 'signaling pathway' named entity 'phosphorylation' named entity 'phosphorylation' named entity 'phosphorylation' named entity 'IFN-α/β' named entity 'type I interferon' named entity 'IFN' named entity 'Golgi apparatus' named entity 'serum' named entity 'BRAF' named entity 'MAPK/ERK pathway' named entity 'BRAF' named entity 'U0126' named entity 'gene' named entity 'MAPK/ERK pathway'

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