Nature CommunicationsMicrobiologyPeer-reviewed journal article
Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 variants
Sarah Hélène MerklingiD, Élodie CouderciD, Anna Beth CristiD, Stéphanie DaboiD, Josquin DaroniD, Natapong JupatanakuliD, Myriam BurckbuchleriD, Thomas VialiD, Odile SismeiroiD, Rachel LegendreiD, Adrien PainiD, Hugo VaretiD, Davy JiolleiD, Diégo AyalaiD, Christophe PaupyiD, Éric MaroisiD, Louis LambrechtsiD
Abstract
The mosquito Aedes aegypti is the primary vector for dengue virus (DENV), which infects millions of people annually. Variability in DENV susceptibility among wild Ae. aegypti populations is governed by genetic factors, but specific causal variants are unknown. Here, we identify a cytochrome P450-encoding gene (CYP4G15) whose variants drive differences in DENV susceptibility in a natural Ae. aegypti population. CYP4G15 is transiently upregulated in DENV-resistant midguts, while knockdown increases susceptibility, and transgenic overexpression enhances resistance. A naturally occurring 18-base-pair promoter deletion reduces CYP4G15 expression and confers higher DENV susceptibility. The unexpected role of a cytochrome P450 in DENV susceptibility challenges the long-standing focus on canonical immune pathways and opens new avenues for understanding antiviral defense and DENV transmission in mosquitoes.
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