dc.contributor.author | Kundlacz, Cindy | |
dc.contributor.author | Van Rijn, Piet A. | |
dc.contributor.author | Pourcelot, Marie | |
dc.contributor.author | Fablet, Aurore | |
dc.contributor.author | Da Silva Moraes, Rayane Amaral | |
dc.date.accessioned | 2019-09-02T11:25:25Z | |
dc.date.available | 2019-09-02T11:25:25Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Kundlacz, C. et al. 2019. Novel function of Bluetongue virus NS3 protein in regulation of the MAPK/ERK signaling pathway. Journal of virology, 93(16): Article no e00336. [https://doi.org/10.1128/JVI.00336-19] | en_US |
dc.identifier.issn | 0022-538X | |
dc.identifier.issn | 1098-5514 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/33270 | |
dc.identifier.uri | https://jvi.asm.org/content/93/16/e00336-19 | |
dc.identifier.uri | https://doi.org/10.1128/JVI.00336-19 | |
dc.description.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 nonstructural protein NS3 (BTV-NS3), is able to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, as assessed by phosphorylation levels of ERK1/2 and the translation initiation factor eukaryotic translation initiation factor 4E (eIF4E). 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 in the MAPK/ERK pathway, as a new cellular interactor of BTV-NS3. BRAF silencing led to a significant decrease in the MAPK/ERK activation by BTV, supporting a model wherein BTV-NS3 interacts with BRAF to activate this signaling cascade. This positive regulation acts independently of the role of BTV-NS3 in counteracting the induction of the alpha/beta interferon response. 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. Altogether, our data provide molecular mechanisms that unravel a new essential function of NS3 during BTV infection | en_US |
dc.language.iso | en | en_US |
dc.publisher | ASM | en_US |
dc.subject | MAP kinases | en_US |
dc.subject | Reoviridae | en_US |
dc.subject | interferons | en_US |
dc.subject | Molecular virus-host interactions | en_US |
dc.subject | Virulence factors | en_US |
dc.title | Novel function of Bluetongue virus NS3 protein in regulation of the MAPK/ERK signaling pathway | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 24551287 - Van Rijn, Petrus Antonius | |