Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti

Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24475-24483. doi: 10.1073/pnas.1914814117. Epub 2020 Sep 10.


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.

Keywords: Wolbachia; flavivirus; lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes / chemistry
  • Aedes / metabolism
  • Aedes / microbiology*
  • Aedes / virology*
  • Animals
  • Carnitine / chemistry
  • Carnitine / metabolism*
  • Female
  • Mosquito Vectors / chemistry
  • Mosquito Vectors / metabolism
  • Mosquito Vectors / microbiology
  • Mosquito Vectors / virology
  • Wolbachia / physiology*
  • Zika Virus / physiology*


  • Carnitine