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

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Manokaran, G; Flores, HA; Dickson, CT; Narayana, VK; Kanojia, K; Dayalan, S; Tull, D; McConville, MJ; Mackenzie, JM; Simmons, CPDate
2020-09-29Source Title
Proceedings of the National Academy of Sciences of USAPublisher
NATL ACAD SCIENCESUniversity of Melbourne Author/s
McConville, Malcolm; Mackenzie, Jason; Narayana, Vinod; Simmons, CameronAffiliation
Biochemistry and Molecular BiologyMelbourne School of Population and Global Health
Microbiology and Immunology
Bio21
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Manokaran, 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 Status
Open AccessAbstract
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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