Wolbachia-infected mosquitoes are refractory to flavivirus infections, but the role of lipids in Wolbachia-mediated virus blocking remains to be elucidated. Here, we use liquid chromatography mass spectrometry to provide a comprehensive picture of the lipidome of Aedes aegypti (Aag2) cells infected with Wolbachia only, either dengue or Zika virus only, and Wolbachia-infected Aag2 cells superinfected with either dengue or Zika virus. This approach identifies a class of lipids, acyl-carnitines, as being down-regulated during Wolbachia infection. Furthermore, treatment with an acyl-carnitine inhibitor assigns a crucial role for acyl-carnitines in the replication of dengue and Zika viruses. In contrast, depletion of acyl-carnitines increases Wolbachia density while addition of commercially available acyl-carnitines impairs Wolbachia production. Finally, we show an increase in flavivirus infection of Wolbachia-infected cells with the addition of acyl-carnitines. This study uncovers a previously unknown role for acyl-carnitines in this tripartite interaction that suggests an important and broad mechanism that underpins Wolbachia-mediated pathogen blocking.

感染了Wolbachia的蚊子对黄病毒没有抵抗力，但脂质在Wolbachia介导的病毒阻断中的作用尚待阐明。在这里，我们使用液相色谱-质谱提供的脂质组的全貌埃及伊蚊（Aag2）感染细胞的Wolbachia只而已，无论是登革热或兹卡病毒和沃尔巴克氏体感染的Aag2有两种或登革热病毒兹卡细胞superinfected。这种方法确定了一类脂质，酰基肉碱，在沃尔巴克病期间被下调感染。此外，用酰基肉碱抑制剂进行的治疗对于酰基肉碱在登革热和寨卡病毒的复制中起着至关重要的作用。相反，酰基肉碱的消耗增加了沃尔巴克氏菌的密度，而市售的酰基肉碱的添加损害了沃尔巴克菌的产量。最后，我们发现，添加酰基肉碱后，黄病毒感染的Wolbachia感染细胞数量增加。这项研究发现了酰基肉碱在这种三重相互作用中的先前未知的作用，表明了支持沃尔巴克氏菌介导的病原体阻断的重要而广泛的机制。