PT  - JOURNAL ARTICLE
AU  - Couderc, Elodie
AU  - Crist, Anna B.
AU  - Daron, Josquin
AU  - Varet, Hugo
AU  - van Hout, Femke A. H.
AU  - Miesen, Pascal
AU  - Palatini, Umberto
AU  - Dabo, Stéphanie
AU  - Vial, Thomas
AU  - Lambrechts, Louis
AU  - Merkling, Sarah H.
TI  - <em>Aedes aegypti VLG-1</em> challenges the assumed antiviral nature of <em>Vago</em> genes
AID  - 10.1101/2024.07.01.601473
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.07.01.601473
4099  - http://biorxiv.org/content/early/2024/10/30/2024.07.01.601473.short
4100  - http://biorxiv.org/content/early/2024/10/30/2024.07.01.601473.full
AB  - Arthropod-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, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown. We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquito’s body was slightly impaired, albeit not altering virus transmission rates. Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.Competing Interest StatementThe authors have declared no competing interest.