Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti.
Gayathri ManokaranHeather A FloresConor T DicksonVinod K NarayanaKomal KanojiaSaravanan DayalanDedreia TullMalcolm J McConvilleJason M MackenzieCameron P SimmonsPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.
Keyphrases
- aedes aegypti
- zika virus
- dengue virus
- fatty acid
- induced apoptosis
- mass spectrometry
- liquid chromatography
- cell cycle arrest
- magnetic resonance
- signaling pathway
- computed tomography
- magnetic resonance imaging
- endoplasmic reticulum stress
- oxidative stress
- high resolution
- cell death
- transcription factor
- pi k akt
- solid phase extraction