Biology subjects

Sourisseau, M.

Publications and source records attributed to Sourisseau, M..

9 recordsLinked to original sources

bioRxiv2026

An RNA-centric interactomics screen identifies novel proviral and antiviral genome binding interactors for tick-borne encephalitis virus

The tick-borne encephalitis virus (TBEV), which belongs to the Orthoflavivirus genus, is a medically significant arbovirus in Europe and Asia. Despite distinct pathobiological outcomes, arboviruses have evolved specific strategies to co-opt cellular factors for replication and immune evasion, that involve both viral proteins and viral RNA. The RNA genome of TBEV, as both the substrate for genome replication and translation and a designated target for innate antiviral immunity, is a nexus for interactions with the proteome of host cells. Nonetheless, the molecular bases of these interactions and their implications for the replicative cycle of TBEV remain poorly understood. To create an inventory of such interactions and gain understanding of their functional import, we have resolved the set of cellular proteins bound to TBEV RNA in infected human cells using an agnostic RNA-centric approach. Functional annotation of the resulting core interactome of 215 human host factors showed that viral RNA is deeply embedded in multiple cellular pathways, including those related to RNA and protein metabolism, cytoskeletal scaffolding, vesicle trafficking and innate antiviral immunity. For selected human interactors, we addressed their impact on TBEV infection in gene knockdown experiments, thereby identifying multiple restriction and dependency factors. These included sensors and effectors of innate immune pathways, as well as epitranscriptomic modifiers. Among the former, the dynamin-like GTPase MX2 protein, an interferon-stimulated gene with antiviral activity against multiple viruses including mosquito-borne orthoflaviviruses, displayed unexpected proviral activity against TBEV and a second tick-borne orthoflavivirus. Among the latter, WDR4, the non-catalytic component of the METTL1-WDR4 methyltransferase complex, emerged as a restriction factor with broad-spectrum activity against arboviruses belonging to multiple families of positive-strand RNA viruses. In conclusion, this first description of the RNA interactome of a tick-borne orthoflavivirus illuminates the molecular interactions that underpin TBEV infection of human cells, which taken together reflect both the common ancestry of tick- and mosquito-borne orthoflaviviruses and their considerable evolutionary divergence.

molecular biology↗

bioRxiv2026

Molecular dialogue between Orthonairovirus and tick: RNA-protein interactome of Hazara virus, a BSL2 model of Crimean-Congo Hemorrhagic Fever virus, in Hyalomma cells

Climate change and ecosystem collapse promote geographic expansion of vector-borne diseases, as witnessed by the recent incursions into Spain of the virus responsible for Crimean-Congo hemorrhagic fever (CCHFV). CCHFV is maintained in a tick-vertebrate cycle, principally involving ticks of the genus Hyalomma. Faced with the spread of Hyalomma ticks, and therefore the threat of a natural introduction of CCHFV into Western Europe, appropriate surveillance tools and control measures need to be implemented. It is both within and by the tick that CCHFV is maintained and spread in the environment. Despite prolonged portage of the virus, the tick is not overtly affected by CHFV infection. One of the prerequisites in conceiving control strategies is to understand the molecular mechanisms that intimately link the virus to its arthropod host. Despite the central role of the tick in the biology of CCHFV, these mechanisms are ill-defined, owing in part to the constraints associated with handling CCHFV-infected ticks in biosafety level 4 containment. In this study, we established the network of interactions between the S segment of the RNA genome Hazara virus (HAZV), a BSL-2 model of CCHFV, and Hyalomma proteins using ChIRP-MS technique. We identified 166 tick proteins, 21 of which have been described as RNA-binding proteins. Gene ontology and pathway enrichment analyses revealed that the S segment RNA interacts predominantly with mitochondrial proteins that belong to various mitochondrial metabolic pathways.

microbiology↗

bioRxiv2024

Phytochromes Enable Social Behavior in Marine Diatoms

The phytochrome superfamily, a group of proteins that enable some organisms to detect changes in light intensity and quality, is widespread in terrestrial and marine microbes, fungi, algae, and plants. In terrestrial plants, these photosensory receptors monitor variations in the light environment by sensing red (R) and far-red (FR) regions of the spectrum and trigger important developmental, metabolic, and physiological responses. However, the role of these photosensors in marine microbes, living in environments where, due to absorption of water molecules R and FR radiation does not penetrate beyond the upper few meters, remains controversial. Here, we investigate the role of phytochromes in light perception of the marine diatom Phaeodactylum tricornutum and their involvement in light-driven collective behavior. We perform experiments comparing the social conduct of wild-type and phytochrome knock-out strains to different light wavelengths. Our results show that cell movements become synchronized in a coordinated wobbling dance upon activation of their phytochromes by blue or far-red light, therefore, demonstrating the key role of phytochrome in light-mediated diatom collective behaviour. Furthermore, our experiments suggest that the observed phytochrome-mediated concerted dance implies a form of intercell communication, proposedly mediated by variable R/FR autofluorescence emission in the frequency range of diatom wobbling movements. Our findings provide new insights into communication pathways in aquatic microorganisms and emphasize the importance of social conduct in the sea at all ecological levels.

ecology↗

bioRxiv2023

Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2

The mechanisms utilized by different flaviviruses to evade antiviral functions of interferons are varied and incompletely understood. Using virological approaches, biochemical assays and mass spectrometry analysis, we report here that the NS5 protein of tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV), two related tick-borne flaviviruses, antagonize JAK-STAT signaling through interactions with tyrosine kinase 2 (TYK2). Co-immunoprecipitation (co-IP) experiments, yeast gap-repair assays, computational protein-protein docking and functional studies identified a stretch of 10 residues of the RNA dependent RNA polymerase domain of tick-borne flavivirus NS5, but not mosquito-borne NS5, that is critical for interaction with the TYK2 kinase domain. Additional co-IP assays performed with several TYK2 orthologs revealed that the interaction was conserved across mammal species. In vitro kinase assays showed that TBEV and LIV NS5 reduced the catalytic activity of TYK2. Our results thus illustrate a novel mechanism by which viruses suppress the interferon response. TeaserInhibition of the catalytic activity of a key kinase of the JAK/STAT pathway by a viral protein

microbiology↗

bioRxiv2023

Influence of oceanography and geographic distance on genetic structure: how varying the sampled domain influences conclusions in Laminaria digitata

Understanding the environmental processes shaping connectivity can greatly improve management and conservation actions which are essential in the trailing edge of species distributions. In this study, we used a dataset built from 32 populations situated in the southern limit of the kelp species Laminaria digitata. By extracting data from 11 microsatellite markers, our aim was to (1) refine the analyses of population structure, (2) compare connectivity patterns and genetic diversity between island and mainland populations and (3) evaluate the influence of sampling year, hydrodynamic processes, habitat discontinuity, spatial distance and sea surface temperature on the genetic structure using a distance-based redundancy analysis (db-RDA). Analyses of population structure enabled to identify well connected populations associated to high genetic diversity, and others which appeared genetically isolated from neighboring populations and showing signs of genetic erosion verifying contrasting ecological (and demographic) status in Brittany and the English Channel. By performing db-RDA analyses on various sampling sizes, geographic distance appeared as the dominant factor influencing connectivity between populations separated by great distances, while hydrodynamic processes were the main factor at smaller scale. Finally, Lagrangian simulations enabled to study the directionality of gene flow which has implications on source-sink dynamics. Overall, our results have important significance in regard to the management of kelp populations facing pressures both from global warming and their exploitation for commercial use.

evolutionary biology↗

bioRxiv2022

Integrated protein-protein interaction and RNA interference screens reveal novel restriction and dependency factors for a tick-borne flavivirus in its human host

In Europe, tick-borne encephalitis virus (TBEV) is responsible for severe neurological disease in humans. Like other viruses, TBEV is an obligate intracellular life form whose survival requires subversion of metabolic processes and evasion of anti-viral pathways. This feat is achieved in no small part by binary interactions between dedicated viral proteins and host proteins. Such protein-protein interactions (PPI) constitute molecular determinants of critical pathobiologic traits of viruses, including host-range, zoonotic potential and virulence, and represent realistic targets for anti-viral therapies. To shed light on the pathobiology of TBEV in human, we have resolved the network of PPI established with its human host by interaction proteomics. A high-throughput screen for virus-host PPI was performed involving the complete set of open reading frames of TBEV and the cDNA libraries of Homo sapiens, by means of yeast two-hybrid methodology. We have discovered a large set of virus-host protein-protein interactions concerning 42 different human proteins directly interacting with nine viral proteins. Many of these human interactors have never been linked in the literature to viral infection. The functional significance of the host interactors in viral infection as viral dependency or restriction factors was then characterized in vitro by RNA interference, and their function inferred by bioinformatic analysis. Approximately 40% of the identified human proteins have a significative impact on TBEV viral replication. These are engaged in many biological processes, whose involvement in viral infection is expected for many, but enigmatic for some. Further work will be necessary to gain molecular understanding of how these biological processes support or restrict TBEV replication, and whether they constitute viral vulnerabilities that can be exploited therapeutically.

microbiology↗

bioRxiv2021

Dinophyceae use exudates as weapons against the parasite Amoebophrya sp. (Syndiniales)

Parasites of the genus Amoebophrya sp. are important contributors to marine ecosystems and can be determining factors in the demise of blooms of Dinophyceae, including microalgae commonly responsible for toxic red tides. Yet they rarely lead to the total collapse of Dinophyceae blooms. The addition of resistant Dinophyceae (Alexandrium minutum or Scrippsiella donghaienis) or their exudate into a well-established host-parasite culture (Scrippsiella acuminata-Amoebophrya sp.) mitigated the success of the parasite and increased the survival of the sensitive host. Effect were mediated via water-borne molecules without the need of a physical contact. Severity of the anti-parasitic defenses fluctuated depending on the species, the strain and its concentration, but never totally prevented the parasite transmission. The survival time of Amoebophrya sp. free-living stages (dinospores) decreased in presence of A. minutum but not of S. donghaienis. The progeny drastically decreased with both species. Integrity of the membrane of dinospores was altered by A. minutum which provided a first indication on the mode of action of these anti-parasitic molecules. These results demonstrate that extracellular defenses are an effective strategy against parasites that does not only protect the resistant cells but also have the potential to affect the whole surrounding community.

microbiology↗

bioRxiv2020

Improve Concentration Of Frequency And Time (ConceFT) By Novel Complex Spherical Designs

AO_SCPLOWBSTRACTC_SCPLOWConcentration of frequency and time (ConceFT) is a generalized multitaper algorithm introduced to analyze complicated non-stationary time series. To avoid the randomness in the original ConceFT algorithm, we apply the novel complex spherical design technique to standardize ConceFT, which we coin CQU-ConceFT. The proposed CQU-ConceFT is applied to visualize the spindle structure in the electroencephalogram signal during the N2 sleep stage and other physiological time series.

pathology↗

bioRxiv2019

Deep mutational scanning comprehensively maps how Zika envelope protein mutations affect viral growth and antibody escape

Functional constraints on viral proteins are often assessed by examining sequence conservation among natural strains, but this approach is relatively ineffective for Zika virus because all known sequences are highly similar. Here we take an alternative approach to map functional constraints on Zika viruss envelope (E) protein by using deep mutational scanning to measure how all amino-acid mutations to the protein affect viral growth in cell culture. The resulting sequence-function map is consistent with existing knowledge about E protein structure and function, but also provides insight into mutation-level constraints in many regions of the protein that have not been well characterized in prior functional work. In addition, we extend our approach to completely map how mutations affect viral neutralization by two monoclonal antibodies, thereby precisely defining their functional epitopes. Overall, our study provides a valuable resource for understanding the effects of mutations to this important viral protein, and also offers a roadmap for future work to map functional and antigenic selection to Zika virus at high resolution.\n\nImportanceZika virus has recently been shown to be associated with severe birth defects. The viruss E protein mediates its ability to infect cells, and is also the primary target of the antibodies that are elicited by natural infection and vaccines that are being developed against the virus. Therefore, determining the effects of mutations to this protein is important for understanding its function, its susceptibility to vaccine-mediated immunity, and its potential for future evolution. We completely mapped how amino-acid mutations to E protein affected the viruss ability to grow in cells in the lab and escape from several antibodies. The resulting maps relate changes in the E proteins sequence to changes in viral function, and therefore provide a valuable complement to existing maps of the physical structure of the protein.

microbiology↗