Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti
AuthorManokaran, G; Flores, HA; Dickson, CT; Narayana, VK; Kanojia, K; Dayalan, S; Tull, D; McConville, MJ; Mackenzie, JM; Simmons, CP
Source TitleProceedings of the National Academy of Sciences of USA
PublisherNATL ACAD SCIENCES
University of Melbourne Author/sMcConville, Malcolm; Mackenzie, Jason; Narayana, Vinod; Simmons, Cameron
AffiliationBiochemistry and Molecular Biology
Melbourne School of Population and Global Health
Microbiology and Immunology
Document TypeJournal Article
CitationsManokaran, G., Flores, H. A., Dickson, C. T., Narayana, V. K., Kanojia, K., Dayalan, S., Tull, D., McConville, M. J., Mackenzie, J. M. & Simmons, C. P. (2020). Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117 (39), pp.24475-24483. https://doi.org/10.1073/pnas.1914814117.
Access StatusOpen Access
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.
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