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dc.contributor.authorManokaran, G
dc.contributor.authorFlores, HA
dc.contributor.authorDickson, CT
dc.contributor.authorNarayana, VK
dc.contributor.authorKanojia, K
dc.contributor.authorDayalan, S
dc.contributor.authorTull, D
dc.contributor.authorMcConville, MJ
dc.contributor.authorMackenzie, JM
dc.contributor.authorSimmons, CP
dc.date.accessioned2020-11-17T03:38:08Z
dc.date.available2020-11-17T03:38:08Z
dc.date.issued2020-09-29
dc.identifierpii: 1914814117
dc.identifier.citationManokaran, 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.
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/11343/251564
dc.description.abstractWolbachia-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.
dc.languageEnglish
dc.publisherNATL ACAD SCIENCES
dc.titleModulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti
dc.typeJournal Article
dc.identifier.doi10.1073/pnas.1914814117
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentBio21
melbourne.source.titleProceedings of the National Academy of Sciences of USA
melbourne.source.volume117
melbourne.source.issue39
melbourne.source.pages24475-24483
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1464483
melbourne.contributor.authorMcConville, Malcolm
melbourne.contributor.authorMackenzie, Jason
melbourne.contributor.authorNarayana, Vinod
melbourne.contributor.authorSimmons, Cameron
dc.identifier.eissn1091-6490
melbourne.accessrightsOpen Access


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