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Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature Communications - 12 Aug 2025

Sarah H Merkling, Elodie Couderc, Anna B Crist, Stéphanie Dabo, Josquin Daron, Natapong Jupatanakul, Myriam Burckbuchler, Thomas Vial, Odile Sismeiro, Rachel Legendre, Adrien Pain, Hugo Varet, Davy Jiolle, Diego Ayala, Christophe Paupy, Eric Marois, Louis Lambrechts

Link to Pubmed [PMID] – 40796739

Link to HAL – pasteur-05212693

Link to DOI – 10.1038/s41467-025-62693-y

Nature Communications, 2025, 16 (1), pp.7468. ⟨10.1038/s41467-025-62693-y⟩

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 genetic 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.