DmGAR · Uncovering antiviral mechanisms in the insect gut during oral virus infection
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-01-01 → 2023-12-31
- EU contribution
- €196,708
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Uncovering antiviral mechanisms in the insect gut during oral virus infection
As the first tissue barrier encountered by orally acquired pathogens, the intestinal epithelium plays a crucial role in responding to and controlling viral infections. Gaining a greater understating of viral infections in the intestine is an important goal for several reasons. Enteric viral infections are a major cause of morbidity and mortality in humans as they are associated with numerous inflammatory conditions including inflammatory bowel disease and colorectal cancer. Moreover, mosquito-transmitted viruses such as dengue virus, chikungunya virus, and zika virus must first successfully infect the mosquito intestine to initiate their transmission cycles. Similarly, enteric viral infections in insect vectors of pathogenic plant-infecting viruses have a major impact on agricultural productivity. The goal of DmGAR was to provide a comprehensive understanding of host-virus interactions during enteric viral infection in the Drosophila melanogaster model. We sought to answer the following questions: What are the dynamics and outcomes of viral infection in the intestine? What are the genetic responses to enteric viral infection? How does viral infection impact intestinal homeostasis? By addressing these questions our goal was to uncover crucial roles of the gut epithelium in responding to viral infection and to understand how the gut response to infection influences organismal health.
Data: CORDIS, © European Union
Project 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
Original text from CORDIS.
Participants
- INSTITUT PASTEUR · ParisCoordinatorFrance
Links
- View on CORDIS
- DOI: 10.3030/101024099
- https://github.com/Jcnigg/Public-Repository-for-the-MSCA-IF-Project-DmGAR-Grant-Agreement-No.-101024099
Data: CORDIS, © European Union