Biology subjects

Lecollinet, S.

Publications and source records attributed to Lecollinet, S..

3 recordsLinked to original sources

bioRxiv2024

Relevance of the synergy of surveillance and populational networks in understanding the Usutu virus outbreak within common blackbirds (Turdus merula) in Metropolitan France, 2018

Usutu virus (USUV) was first isolated in Africa in 1959 and has since spread to and through Europe with a typical enzootic mosquito-bird cycle. In France, it was first detected in birds in 2015, but during summer 2018 the spread of USUV was particularly significant throughout the country, killing mainly common blackbirds (Turdus merula) and to a lesser extent great grey owls (Strix nebulosa), among other captive and non-captive wild bird species. Previous studies of USUV in France have focused on reconstructing pathways of introduction, but not on structural aspects of virus spread within the country. Data (RT-PCR of geolocated dead birds) on this 2018 outbreak were collected through both an event-based wildlife network named SAGIR and the health surveillance of the French-speaking Association of Zoo Veterinarians (AFVPZ). In addition, common blackbird populations could be monitored through another network (REZOP). Statistical analysis (spatial, temporal, spatiotemporal and environmental determinants) of the SAGIR and AFVPZ network data helped to highlight the early appearance of separate large clusters of USUV cases in mid-July 2018, the subsequent diffusion into smaller and secondary clusters at the end of August 2018, and a meanwhile enlargement of the first clusters with an increase in the number of cases. High human density (top 10.5% densest areas in France) and wetland concentration (top 19.3% most likely wetland areas) were significant factors in USUV case locations. Using generalised additive mixed models on REZOP data, we also highlighted the decline in common blackbird population trends in areas with medium and even more with high USUV pressure (areas defined based on SAGIR-AFVPZ data) following the 2018 outbreak (respectively -7.4% [-11.4; -3.9]95% and -15.7% [-16.2; -9.1]95%). A large area (radius [~]150 km) in the centre and centre-west of France, and smaller areas in the south-east, north and north-east of France (each with a radius [~] 50 km) were particularly affected. We conclude on the importance to work with synergistic networks to assess infection spread in wild bird species, as well as the negative impact of an emerging arbovirus. The responsiveness of such a network system could be improved by automating alerts.

ecology↗

bioRxiv2019

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection.

Tick-borne encephalitis virus (TBEV) is a member of the Flaviviridae family, Flavivirus genus, which includes several important human pathogens. It is responsible for neurological symptoms that may cause permanent disability or death, and, from a medical point of view, is the major arbovirus in Central/Northern Europe and North-eastern Asia. TBEV tropism is critical for neuropathogenesis, yet, little is known about the molecular mechanisms that govern the susceptibility of human brain cells to the virus. In this study, we sought to establish and characterize a new in vitro model of TBEV infection in the human brain and to decipher cell type-specific innate immunity and its relation to TBEV tropism and neuropathogenesis. We showed that infection of neuronal/glial cultures derived from human fetal neural progenitor cells (hNPCs) mimicked three major hallmarks of TBEV infection in the human brain, namely, preferential neuronal tropism, neuronal death and astrogliosis. We also showed that these cells had conserved their capacity to build an antiviral response against TBEV. TBEV-infected neuronal/glial cells, therefore, represented a highly relevant pathological model. By enriching the cultures in either human neurons or astrocytes, we further demonstrated qualitative and quantitative differential innate immune responses in the two cell types that correlated with their particular susceptibility to TBEV. Our results thus reveal that cell type-specific innate immunity is likely to contribute to shaping TBEV tropism for human brain cells. They offer a new in vitro model to further study TBEV-induced neuropathogenesis and improve our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells.\n\nAuthor summaryTick-borne encephalitis virus (TBEV), a neurotropic Flavivirus that is responsible for encephalitis in humans, is of growing concern in Europe. Indeed, over the last two decades the number of reported cases has continuously increased and the virus has spread into new geographical areas. Whereas it is well established that neurons are the main target of TBEV in the human brain, the mechanisms that underlie this preferential tropism have not yet been elucidated. Here, we used neuronal/glial cells derived from human fetal neural progenitors to establish and characterize a new in vitro pathological model that mimics major hallmarks of TBEV infection in vivo; namely, neuronal tropism, neuronal death and astrogliosis. Using this highly relevant model, we showed that human neurons and astrocytes were both capable of developing an innate immune response against TBEV, but with dissimilar magnitudes that correlated with differential susceptibility to TBEV. Our results thus revealed that TBEV tropism for subsets of human brain cells is likely to depend on cell-type specific innate immunity. This improves our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells and may help guide development of future therapies.

microbiology↗

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↗