Biology subjects

Viarouge, C.

Publications and source records attributed to Viarouge, C..

3 recordsLinked to original sources

bioRxiv2025

How an arthropod-borne virus manages host switches: exploration of host-specific mutations and gene formula in bluetongue virus

Arthropod-borne viruses, also known as arboviruses, cause disease worldwide. These viruses alternate between vertebrates and arthropods, facing distinct selection pressures in each host type. Surprisingly, whether specific mechanisms facilitate host alternation remains unclear. Here, we use bluetongue virus (BTV) as a model to investigate two phenomena potentially facilitating host alternation: adaptive mutations and genome formula variation (GFV). First, we searched for mutations indicative of host adaptation in cattle, sheep, and midges infected during an epizooty. We found a limited number of parallel mutations. This result suggests that adaptive mutations are not a main mechanism facilitating host alternation in BTV. Second, we investigated a link of GFV with a proxy of viral fitness, the speed of virus dissemination in midges. We analyzed the genome formula (GF) in experimentally-infected Culicoides imicola midges, either with an infection disseminated into the head or not. GFs differed between dissemination levels, suggesting a link between GF and the speed of virus dissemination. Finally, we investigated the mechanisms underlying GF generation. Currently, two scenarios have been proposed: random generation followed by selection, or directed generation through molecular mechanisms. To limit the influence of selection, we analyzed the GF after a single replication cycle in cell culture. GF values converged towards specific values among replicates. Moreover, GFs differed between arthropod and vertebrate cells. Thus, GF generation is not purely stochastic and is probably influenced by host-specific mechanisms. Overall, our findings highlight GFV as a potential mechanism facilitating BTV alternation across hosts, but not classical mutation-driven evolution. Author SummaryArthropod-borne viruses are important public health problems in the world. These viruses follow a complex cycle involving alternation between arthropods and vertebrates. Surprisingly, we know little on the mechanisms that facilitate alternation between the two host types. Knowledge on such mechanisms could allow the development of antiviral tools. Here, using Bluetongue virus as a model, we investigated two potential mechanisms facilitating alternation: adaptive mutations and genome formula variation (GFV). We found limited evidence for host-specific mutations in natural populations. We observed a potential link between GFV and viral fitness. Moreover, our results suggest that molecular mechanisms generate GFV in a host-specific way from the first round of cell infection.

microbiology↗

bioRxiv2019

Evolutionary stasis of an RNA virus indicates arbovirus re-emergence triggered by accidental release

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an insect-borne virus of ruminants, emerged in livestock in Northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of Euros. Though the outbreak was successfully controlled through vaccination by early 2010, puzzlingly a closely-related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this period without replication, we conclude that the second outbreak was most likely initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.

evolutionary biology↗

bioRxiv2019

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

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. ImportanceBluetongue 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.

microbiology↗