AVago-like gene enhances dengue and Zika virus dissemination inAedes aegypti

Abstract

ABSTRACTArthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, theAedes aegyptimosquito. In arthropods, genes of theVagofamily are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role ofVagogenes upon virus infection inAe. aegyptiis largely unknown. We conducted a phylogenetic analysis of theVagogene family in Diptera, which led us to focus on aVago-like gene that we namedVLG-1. Using CRISPR/Cas9-mediated gene editing, we generated aVLG-1mutant line ofAe. aegyptithat revealed a proviral effect of this gene upon DENV and ZIKV infection. In the absence ofVLG-1, virus dissemination throughout the mosquito’s body was impaired, albeit not altering virus transmission rates. A tissue-specific transcriptome analysis revealed that the loss ofVLG-1impacted numerous biological processes potentially linked to viral replication, such as the oxidative stress response. Our results challenge the conventional understanding ofVago-like genes as antiviral factors and underscores the need for further research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.