Aedes aegypti mosquitoes are the main vectors of many arboviruses of medical significance, including dengue virus. The vector competence of mosquitoes, defined as their ability to acquire and subsequently transmit a virus, is governed by molecular factors of the vector that are poorly understood. Identifying and characterising these factors is an important prerequisite for the development of new arbovirus prevention strategies targeting vector-virus interactions. In mammals, the first response to a viral infection relies on interferon, a molecule secreted upon infection which activates an antiviral state in the neighbouring cells. A gene called Vago was shown to share an interferon-like function in flies and Culex mosquitoes.
This project aims to characterise the role of Vago homologs (Vago1 and Vago2) in Ae. aegypti during dengue virus infection. Our approach relies on reverse genetic tools including a Vago1-knockout line generated by CRISPR/Cas9 gene editing. Our preliminary data revealed that in contrast with what was observed in other insects, Vago1 is proviral during dengue virus infection of Ae. aegypti and favours viral dissemination in the vector’s body. Our analyses showed that this proviral effect is not mediated by the regulation of inducible immune pathways, or dependent on the double-stranded RNA sensor Dicer2. To follow up on this work, we aim to uncover the molecular mechanisms underlying the proviral effect of Ae. aegypti Vago1 on dengue virus.
