Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 promoter variants.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40796739.
- Also identified by DOI 10.1038/s41467-025-62693-y and PMC identifier 12343897.
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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.
Medical subject headings
- Aedes
- Promoter Regions, Genetic
- Cytochrome P-450 Enzyme System
- Dengue Virus
- Mosquito Vectors
- Dengue
- Insect Proteins