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Uncovering antiviral mechanisms in the insect gut during oral virus infection

Objective

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

Call for proposal

H2020-MSCA-IF-2020
See other projects for this call

Funding Scheme

MSCA-IF-EF-ST - Standard EF

Coordinator

INSTITUT PASTEUR
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15
France
Activity type
Research Organisations
EU contribution
€ 196 707,84