埃及伊蚊对登革病毒的易感性与天然细胞色素P450启动子变体有关。
Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 promoter variants.
作者信息
Merkling Sarah H, Couderc Elodie, Crist Anna B, Dabo Stéphanie, Daron Josquin, Jupatanakul Natapong, Burckbuchler Myriam, Vial Thomas, Sismeiro Odile, Legendre Rachel, Pain Adrien, Varet Hugo, Jiolle Davy, Ayala Diego, Paupy Christophe, Marois Eric, Lambrechts Louis
机构信息
Institut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions Unit, Paris, France.
Sorbonne Université, Collège Doctoral, Paris, France.
出版信息
Nat Commun. 2025 Aug 12;16(1):7468. doi: 10.1038/s41467-025-62693-y.
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.
埃及伊蚊是登革病毒（DENV）的主要传播媒介，每年有数百万人感染该病毒。野生埃及伊蚊种群对DENV易感性的差异受遗传因素控制，但具体的因果变异尚不清楚。在此，我们鉴定出一个编码细胞色素P450的基因（CYP4G15），其遗传变异导致了自然埃及伊蚊种群对DENV易感性的差异。CYP4G15在对DENV具有抗性的中肠中短暂上调，而敲低该基因会增加易感性，转基因过表达则增强抗性。一种自然发生的18个碱基对的启动子缺失会降低CYP4G15的表达，并赋予更高的DENV易感性。细胞色素P450在DENV易感性中发挥的意外作用挑战了长期以来对经典免疫途径的关注，并为理解蚊子的抗病毒防御和DENV传播开辟了新途径。
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