Definition: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Input: Bluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide 27 range of wild and domestic ruminants. In this report, we showed that BTV, through its virulence 28 non-structural protein NS3 (BTV-NS3), is able to activate the MAPK/ERK pathway. In 29 response to growth factors, the MAPK/ERK pathway activates cell survival, differentiation, 30 proliferation and protein translation but can also lead to the production of several inflammatory 31 cytokines. By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis 32 from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein 33 kinase B-Raf (BRAF), a crucial player of the MAPK/ERK pathway, as a new cellular interactor 34 of BTV-NS3. BRAF silencing led to a significant decrease of the MAPK/ERK activation by 35 BTV supporting a model where BTV-NS3 interacts with BRAF to activate this signaling 36 cascade. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the 37 MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be 38 specific to BTV compared to other members of Orbivirus genus. Inhibition of MAPK/ERK 39 pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its 40 own replication. Therefore, the activation of the MAPK/ERK pathway by BTV-NS3 could 41 benefit to BTV replication by promoting its own viral protein synthesis but could also explain 42 the deleterious inflammation associated with tissue damages as already observed in severe cases 43 of BT disease. Altogether, our data provide molecular mechanisms to explain the role of BTV-44 NS3 as a virulence factor and determinant of pathogenesis. 45 author/funder. All rights reserved. No reuse allowed without permission. Bluetongue Virus (BTV) is responsible of the non-contagious arthropod-borne disease 48 Bluetongue (BT) transmitted to ruminants by blood-feeding midges. Despite the fact that BTV 49 has been extensively studied, we still have little understanding of the molecular determinants 50 of BTV virulence. In this report, we found that the virulence protein NS3 interacts with BRAF, 51 a key component of the MAPK/ERK pathway. In response to growth factors, this pathway 52 promotes cell survival, increases protein translation but also contributes to the production of 53 inflammatory cytokines. We showed that BTV-NS3 enhances the MAPK/ERK pathway and 54 this activation is BRAF-dependent. Our results demonstrate, at the molecular level, how a 55 single virulence factor has evolved to target a cellular function to ensure its viral replication. 56 On the other hand, our findings could also explain the deleterious inflammation associated with 57 tissue damages as already observed in severe cases of BT disease. 58 author/funder. All rights reserved. No reuse allowed without permission.

Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway 2 3