Competition between viruses and Wolbachia for host lipids is a proposed mechanism of Wolbachia-mediated virus blocking in insects. Yet, the metabolomic interaction between virus and symbiont within the mosquito has not been clearly defined. We compare the lipid profiles of Aedes aegypti mosquitoes bearing mono- or dual-infections of the Wolbachia wMel strain and dengue virus serotype 3 (DENV3). We found metabolic signatures of infection-induced intracellular events but little evidence to support direct competition between Wolbachia and virus for host lipids. Lipid profiles of dual-infected mosquitoes resemble those of DENV3 mono-infected mosquitoes, suggesting virus-driven modulation dominates over that of Wolbachia. Interestingly, knockdown of key metabolic enzymes suggests cardiolipins are host factors for DENV3 and Wolbachia replication. These findings define the Wolbachia-DENV3 metabolic interaction as indirectly antagonistic, rather than directly competitive, and reveal new research avenues with respect to mosquito × virus interactions at the molecular level.

病毒和Wolbachia之间对宿主脂质的竞争是Wolbachia介导的昆虫病毒阻断机制。然而，病毒与蚊子内共生体之间的代谢相互作用尚未明确定义。我们比较了携带Wolbachia w Mel 菌株和登革热病毒血清型 3 (DENV3)单一或双重感染的埃及伊蚊的脂质谱。我们发现了感染诱导的细胞内事件的代谢特征，但几乎没有证据支持沃尔巴克氏体和病毒之间对宿主脂质的直接竞争。双重感染蚊子的脂质特征类似于 DENV3 单一感染蚊子的脂质特征，表明病毒驱动的调节优于沃尔巴克氏菌。有趣的是，关键代谢酶的敲低表明心磷脂是 DENV3 和Wolbachia复制的宿主因子。这些发现将Wolbachia -DENV3 代谢相互作用定义为间接拮抗性，而不是直接竞争性，并在分子水平上揭示了蚊与病毒相互作用的新研究途径。