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

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-08-12 DOI:10.1038/s41467-025-62693-y

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

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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.

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埃及伊蚊对登革病毒的易感性与天然细胞色素P450启动子变异有关

埃及伊蚊是登革热病毒（DENV）的主要媒介，每年感染数百万人。野生伊蚊对登革热病毒易感性的变异。埃及伊蚊种群受遗传因素控制，但具体的致病变异尚不清楚。在这里，我们鉴定了一个细胞色素p450编码基因（CYP4G15），其遗传变异驱动了天然伊蚊DENV易感性的差异。蚊数量。CYP4G15在denv抗性中短暂上调，敲低增加易感性，转基因过表达增强抗性。自然发生的18碱基对启动子缺失减少了CYP4G15的表达，并赋予了更高的DENV易感性。细胞色素P450在登革热病毒易感性中的意外作用挑战了长期以来对典型免疫途径的关注，并为理解登革热病毒在蚊子中的抗病毒防御和传播开辟了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.