Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 promoter variants

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 and Louis Lambrechts ()
Additional contact information
Sarah H. Merkling: Insect-Virus Interactions Unit
Elodie Couderc: Insect-Virus Interactions Unit
Anna B. Crist: Insect-Virus Interactions Unit
Stéphanie Dabo: Insect-Virus Interactions Unit
Josquin Daron: Insect-Virus Interactions Unit
Natapong Jupatanakul: Insect-Virus Interactions Unit
Myriam Burckbuchler: INSERM U1257
Thomas Vial: Insect-Virus Interactions Unit
Odile Sismeiro: Education Department
Rachel Legendre: Bioinformatics and Biostatistics Hub
Adrien Pain: Bioinformatics and Biostatistics Hub
Hugo Varet: Bioinformatics and Biostatistics Hub
Davy Jiolle: Insect-Virus Interactions Unit
Diego Ayala: CNRS
Christophe Paupy: CNRS
Eric Marois: INSERM U1257
Louis Lambrechts: Insect-Virus Interactions Unit

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62693-y

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DOI: 10.1038/s41467-025-62693-y

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