Éléments transposables et défense antivirale chez le moustique Aedes aegypti

Aedes aegypti, the yellow fever mosquito, is the primary vector of several arthropod-borne viruses (arboviruses) affecting humans, among which dengue virus (DENV) causes millions of symptomatic infections each year. Underlying DENV transmission is the unparalleled vector competence, i.e., physiological ability to become infected and transmit pathogens, of Ae. aegypti. Curiously, the genome of Ae. aegypti contains a large proportion of transposable elements (TEs) - a trait shared with other mosquitoes implicated in arbovirus transmission. TEs and arboviruses encounter the same small RNA-based regulatory pathways and TE- derived reverse transcriptases (RTs) have been shown to impact the outcome of arbovirus infection in other insects. Whether abundant TEs enable Ae. aegypti to be an exceptionally competent vector is the overarching question of this thesis. In the first chapter, we focused on the role of the small interfering RNA (siRNA) pathway, a known antiviral pathway, in TE regulation. We found that TE-derived siRNAs are produced in vivo, but their role in regulating TE expression was negligible. Given the limited impact of siRNAs seen in vivo also on arbovirus vector competence, we conclude that TEs are unlikely to render Ae. aegypti a highly competent vector through saturation of the siRNA pathway. In the second chapter, we searched for correlations between TE expression and DENV RNA load in transcriptomic data from individual mosquito midguts. We found primarily negative correlations involving TEs that encode an RT. However, these correlations were context- specific and could not be confirmed in repeat experiments due to the technical challenges of accurately quantifying the expression of individual TEs. We postulate that TEs may have a protective effect during DENV infection in Ae. aegypti but require sequence-independent methods for functional quantification. In the third chapter, we investigated whether somatic RT activity has a dose-dependent effect on DENV infection phenotypes in Ae. aegypti. We employed both natural variation within and between mosquito populations, as well as artificial induction of RT activity through knock- down of Asterix2, a gene identified to regulate somatic RT activity. We found that somatic RT activity in adult Ae. aegypti, although variable between populations, had no meaningful impact on DENV transmission potential. In summary, this thesis explored multiple mechanisms for interactions between TEs and arboviruses in Ae. aegypti but found no evidence of a major effect of TE expression on vector competence. We advocate for deeper characterization of the TEs and their regulatory mechanisms in Ae. aegypti for the generation and testing of future hypotheses.