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The molecular basis of natural antiviral resistance to dengue virus and Zika virus in Aedes aegypti mosquitoes

The main purpose of this project is to characterize the mechanisms required by resistance to dengue virus and Zika virus in mosquitoes. Although major discoveries have been made in understanding resistance to the malaria parasite in the Anopheles mosquito, as well as antiviral defense mechanisms in the fruit fly Drosophila melanogaster, studies in Aedes mosquitoes are still scarce. developed. Studies describing the mechanisms involved in the control of arbovirus infections in the Aedes mosquito have mainly relied on three strategies: (i) the mechanisms described previously in other organisms such as the fruit fly Drosophila melanogaster; (ii) pathways whose transcription is regulated by infection and (iii) unbiased selection using cell lines. These led to important discoveries, but however limited by biased analyzes (retaining mechanisms and pathways requiring regulation at the transcriptional level), or lacking in vivo context (studies on cell lines). Therefore, we do not yet understand the basics of the molecular mechanisms of mosquito resistance to viral infection.

This project offers a unique and daring approach to overcome these limitations by analyzing the mechanisms leading to natural antiviral resistance in adult mosquitoes, independently of conservation or transcriptional regulation. Our preliminary results suggest that respiratory chain complex I regulates resistance to dengue virus, a still unexplored area of antiviral mechanisms. Therefore, our specific approach has a high probability of leading to truly revolutionary discoveries, which could help to provide solutions to the growing problem of viruses transmitted by mosquitoes. In the long term, a clear understanding of antiviral resistance represents a big step towards developing strategies to modulate arbovirus transmission.