TERC - Tremplin-ERC

Genetic basis of genotype-by-genotype specificity in a natural insect vector-virus interaction – GxG

Submission summary

Dengue viruses and their main mosquito vector Aedes aegypti are responsible for the most rapidly advancing, globally dominant vector-borne viral disease of humans. Similar to many other invertebrate host-pathogen systems, successful dengue virus infection in mosquitoes depends on the specific pairing of host and pathogen genotypes. However, the molecular mechanisms behind these genotype-by-genotype (G x G) interactions are unknown. We propose to address this knowledge gap using a natural model of G x G interactions between dengue viruses and Ae. aegypti that we recently established. Taking advantage of this model, our aim is to dissect the mechanisms underlying the early steps of mosquito infection by dengue viruses through several innovative experimental approaches that combine advanced quantitative genetics, high-throughput sequencing, and functional assays in vivo. The project is divided into three parts. In part I, mosquito candidate genes will be identified using genome-wide genetic mapping and gene expression profiling. In part II, putative viral genetic determinants will be identified by experimental virus evolution. In part III, prioritized mosquito and virus candidate genetic polymorphisms from Parts I and II will be functionally validated and characterized using reverse genetics tools, imaging techniques and biochemical assays. Unraveling the molecular mechanisms driving G x G interactions in our model will uncover novel facets of insect-virus interactions. More generally, understanding the genetic basis of host-pathogen specificity is essential to evaluate the risk of pathogen emergence because it largely determines host range and the potential for host shifts.

Project coordination

Louis LAMBRECHTS (INSTITUT PASTEUR )

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IP INSTITUT PASTEUR

Help of the ANR 199,999 euros
Beginning and duration of the scientific project: April 2017 - 24 Months

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