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<p>The mosquito <i>Aedes aegypti</i> is the primary vector for dengue virus (DENV), which infects millions of people annually. Variability in DENV susceptibility among wild <i>Ae. aegypti</i> populations is governed by genetic factors, but specific causal variants are unknown. Here, we identify a cytochrome P450-encoding gene (<i>CYP4G15</i>) whose genetic variants drive differences in DENV susceptibility in a natural <i>Ae. aegypti</i> population. <i>CYP4G15</i> 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 <i>CYP4G15</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月12日

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  • 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

摘要

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.