Description du projet
Disséquer le processus d’infection virale orale
Les insectes constituent des vecteurs de transmission de nombreuses maladies virales de l’homme et des cultures. La transmission fait intervenir l’acquisition orale des virus par les insectes, ce qui suggère que la perturbation de cette voie pourrait constituer une stratégie d’intervention. Le projet DmGAR, financé par l’UE, a pour objectif d’étudier les processus d’infection virale dans l’intestin des insectes. Les chercheurs utiliseront Drosophila melanogaster comme modèle et étudieront l’impact des virus sur les cellules épithéliales de l’intestin. Plus précisément, ils caractériseront le trajet et la cinétique des virus et étudieront les réponses immunitaires de l’hôte dans l’intestin. Les résultats amélioreront nos connaissances actuelles sur les infections virales et ouvriront la voie à de nouvelles stratégies destinées à les contrer.
Objectif
Insect-mediated transmission of viruses is an increasing threat to public health and agricultural productivity in Europe and abroad. New strategies to disrupt transmission of viruses by insects are essential and will be facilitated by knowledge of infection processes and antiviral mechanisms. Most transmission cycles involve oral acquisition of viruses by insects, but knowledge of oral virus infections is limited. Here I propose the DmGAR project (Drosophila melanogaster gut antiviral responses) to provide the first detailed picture of oral virus infection processes in the insect gut. I aim to harness the experimental tractability of D. melanogaster to characterize the dynamics of and genetic responses to oral virus infection and to investigate the interface of viral infection with intestinal physiology.
I hypothesize that stem cell-driven gut epithelium renewal is coordinated with immune mechanisms and is crucial for clearance of oral virus infections. To investigate this hypothesis and accomplish the objectives of DmGAR, I will bring my expertise in host-virus interactions to the Saleh laboratory to study oral infections with naturally infecting viruses of D. melanogaster. I will spatially and temporally define the kinetics and outcomes of infection, determine whether the viruses spread beyond the gut, and if escape from the gut influences infection outcome. Informed by these data, I will evaluate if virus infection impacts rates of epithelial cell death and/or proliferation in the gut and if blockage of epithelial cell turnover influences virus titer, infection outcome, or infection kinetics. I will complement these studies by profiling cell-type-specific gene expression and assaying activation of cell signaling pathways to develop a mechanistic model of the response to oral virus infection in the insect gut. Through these approaches, DmGAR will provide robust and biologically relevant data that will enhance understanding of natural virus infection processes
Champ scientifique
- medical and health scienceshealth sciencespublic health
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health sciencesbasic medicinephysiology
- natural sciencesbiological scienceszoologyentomology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
75724 Paris
France