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

Author

Listed:
  • Sarah H. Merkling

    (Insect-Virus Interactions Unit)

  • Elodie Couderc

    (Insect-Virus Interactions Unit
    Collège Doctoral)

  • 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
    National Center for Genetic Engineering and Biotechnology (BIOTEC))

  • 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
    CNRS
    Centre Interdisciplinaire de Recherches Médicales de Franceville)

  • Diego Ayala

    (CNRS
    Centre Interdisciplinaire de Recherches Médicales de Franceville)

  • Christophe Paupy

    (CNRS
    Centre Interdisciplinaire de Recherches Médicales de Franceville)

  • Eric Marois

    (INSERM U1257)

  • Louis Lambrechts

    (Insect-Virus Interactions Unit)

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.

Suggested Citation

  • 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 V, 2025. "Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 promoter variants," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62693-y
    DOI: 10.1038/s41467-025-62693-y
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