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  • 标题:Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti
  • 本地全文:下载
  • 作者:Gayathri Manokaran ; Heather A. Flores ; Conor T. Dickson
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2020
  • 卷号:117
  • 期号:39
  • 页码:24475-24483
  • DOI:10.1073/pnas.1914814117
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:Wolbachia ; lipids ; flavivirus
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