Summary
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.
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| Web resources: | https://cordis.europa.eu/project/id/101066146 |
| Start date: | 16-01-2023 |
| End date: | 15-01-2025 |
| Total budget - Public funding: | - 195 914,00 Euro |
Cordis data
Original description
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.Status
SIGNEDCall topic
HORIZON-MSCA-2021-PF-01-01Update Date
09-02-2023
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