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

Gayathri Manokaran, Heather A. Flores, Conor T. Dickson, Vinod K. Narayana, Komal Kanojia, Saravanan Dayalan, Dedreia Tull, Malcolm J. McConville, Jason M. Mackenzie, Cameron P. Simmons

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)24475-24483
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number39
DOIs
Publication statusPublished - 29 Sep 2020

Keywords

  • Flavivirus
  • Lipids
  • Wolbachia

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