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
Proceedings of the National Academy of Sciences of USA | NATL ACAD SCIENCES | Published : 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 c..View full abstract
This work was supported by the Wellcome Trust (UK) and the National Health and Medical Research Council (Australia). We thank Dr. Elizabeth A. McGraw for providing the A. aegypti cells and protocols used in maintaining the wMel cell lines. They also thank Drs. Brunda Nijagal and Kirsty McPherson for their invaluable advice throughout this work.