Project description DEENESFRITPL Understanding mechanisms of virus–insect vector interaction helps to predict future outbreaks Prediction of future outbreaks and which viruses and mosquitoes will cause them requires an understanding of the mechanisms of virus susceptibility and mosquito transmission. Funded by the Marie Skłodowska-Curie Actions programme, the ZIKVMosTransmit project aims to identify both the viral and mosquito factors, determining the molecular compatibility of the Zika virus with its vector Aedes aegypti. The study will analyse the mosquito–virus protein interactome to identify and validate the mosquito factors regulating virus susceptibility. The viral genes required for efficient transmission by mosquitoes will be uncovered by a chimeric constructs approach and comparison of transmission efficiency. Project results will provide new information about vector–virus specificity and enhance understanding of mosquito-borne virus emergence. Show the project objective Hide the project objective Objective The public health response to emerging mosquito-borne viral diseases is often inefficient, because the causative agents are recognized and the prevention measures are deployed, only after the disease has spread. To predict which viruses and mosquitoes have the highest potential to cause future outbreaks, understanding the mechanisms determining the virus susceptibility of mosquitoes and the mosquito transmissibility of viruses is needed. In this study, I propose a two-pronged approach to identify both the viral and mosquito factors involved in molecular compatibility between the human pathogenic Zika virus and its main vector Aedes aegypti by combining my skills in molecular virology with the host lab’s expertise in mosquito experimental infections in vivo. First, I will examine the mosquito-virus protein interactome by a proteomics strategy based on cross-linking, immunoaffinity purification and mass spectrometry. Mosquito factors regulating virus susceptibility will be identified by subtractive comparison of virus-binding mosquito proteins between two mosquito strains displaying different levels of Zika virus susceptibility. The correlation between virus susceptibility and the identified proteins will be validated by gene-knockdown assays and expression surveys using a collection of mosquito strains. Second, I will use an innovative reverse genetics system to create chimeric Zika viruses from two parental virus strains with different levels of mosquito transmissibility. The viral genes required for efficient transmission by mosquitoes will be identified by comparing transmissibility between chimeric constructs. Together, this project will provide important new insights into vector-virus specificity and significantly improve our understanding of mosquito-borne virus emergence. Fields of science medical and health scienceshealth sciencespublic healthnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesmicrobiologyvirologynatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological scienceszoologyinvertebrate zoology Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme MSCA-PF - MSCA-PF Coordinator INSTITUT PASTEUR Net EU contribution € 195 914,88 Address Rue du docteur roux 25-28 75724 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window EU contribution No data
