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Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells

Author

Listed:
  • Vincent Geoghegan

    (University of Glasgow
    University of Lancaster)

  • Kirsty Stainton

    (University of Lancaster
    Fera Science Ltd)

  • Stephanie M. Rainey

    (University of Glasgow)

  • Thomas H. Ant

    (University of Glasgow
    University of Lancaster)

  • Adam A. Dowle

    (University of York)

  • Tony Larson

    (University of York)

  • Svenja Hester

    (University of Oxford)

  • Philip D. Charles

    (University of Oxford)

  • Benjamin Thomas

    (University of Oxford)

  • Steven P. Sinkins

    (University of Glasgow
    University of Lancaster)

Abstract

Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of virus inhibition, we here perform proteomic quantification of the effects of Wolbachia in Aedes aegypti mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. Wolbachia-infected cells display a differential cholesterol profile, including elevated levels of esterified cholesterol, that is consistent with perturbed intracellular cholesterol trafficking. Cyclodextrins have been shown to reverse lipid accumulation defects in cells with disrupted cholesterol homeostasis. Treatment of Wolbachia-infected Ae. aegypti cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in Wolbachia-carrying cells, suggesting dengue is inhibited in Wolbachia-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular Wolbachia viral inhibition phenotype and lipid storage genetic disorders.

Suggested Citation

  • Vincent Geoghegan & Kirsty Stainton & Stephanie M. Rainey & Thomas H. Ant & Adam A. Dowle & Tony Larson & Svenja Hester & Philip D. Charles & Benjamin Thomas & Steven P. Sinkins, 2017. "Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00610-8
    DOI: 10.1038/s41467-017-00610-8
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