Geoghegan, V., Stainton, K., Rainey, S. M. , Ant, T. H., Dowle, A. A., Larson, T., Hester, S., Charles, P. D., Thomas, B. and Sinkins, S. P. (2017) Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells. Nature Communications, 8, 526. (doi: 10.1038/s41467-017-00610-8) (PMID:28904344) (PMCID:PMC5597582)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Rainey, Dr Stephanie and Geoghegan, Vincent and Sinkins, Professor Steven and Ant, Dr Thomas |
| Authors: | Geoghegan, V., Stainton, K., Rainey, S. M., Ant, T. H., Dowle, A. A., Larson, T., Hester, S., Charles, P. D., Thomas, B., and Sinkins, S. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Nature Communications |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Nature Communications 8:526 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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