Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells
<p><i>Wolbachia</i> 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 pr...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
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| _version_ | 1826286259380682752 |
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| author | Geoghegan, V Stainton, K Rainey, S Ant, T Dowle, A Larson, T Hester, S Charles, P Thomas, B Sinkins, S |
| author_facet | Geoghegan, V Stainton, K Rainey, S Ant, T Dowle, A Larson, T Hester, S Charles, P Thomas, B Sinkins, S |
| author_sort | Geoghegan, V |
| collection | OXFORD |
| description | <p><i>Wolbachia</i> 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 <i>Wolbachia</i> in <i>Aedes aegypti</i> mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. <i>Wolbachia</i>-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 <i>Wolbachia</i>-infected <i>Ae. aegypti</i> cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in <i>Wolbachia</i>-carrying cells, suggesting dengue is inhibited in <i>Wolbachia</i>-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular <i>Wolbachia</i> viral inhibition phenotype and lipid storage genetic disorders.</p> |
| first_indexed | 2024-03-07T01:41:07Z |
| format | Journal article |
| id | oxford-uuid:96e01271-4126-4879-9615-e2bfbb1e2e04 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:41:07Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:96e01271-4126-4879-9615-e2bfbb1e2e042022-03-26T23:55:56ZPerturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:96e01271-4126-4879-9615-e2bfbb1e2e04EnglishSymplectic Elements at OxfordNature Publishing Group2017Geoghegan, VStainton, KRainey, SAnt, TDowle, ALarson, THester, SCharles, PThomas, BSinkins, S <p><i>Wolbachia</i> 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 <i>Wolbachia</i> in <i>Aedes aegypti</i> mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. <i>Wolbachia</i>-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 <i>Wolbachia</i>-infected <i>Ae. aegypti</i> cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in <i>Wolbachia</i>-carrying cells, suggesting dengue is inhibited in <i>Wolbachia</i>-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular <i>Wolbachia</i> viral inhibition phenotype and lipid storage genetic disorders.</p> |
| spellingShingle | Geoghegan, V Stainton, K Rainey, S Ant, T Dowle, A Larson, T Hester, S Charles, P Thomas, B Sinkins, S Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells |
| title | Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells |
| title_full | Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells |
| title_fullStr | Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells |
| title_full_unstemmed | Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells |
| title_short | Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells |
| title_sort | perturbed cholesterol and vesicular trafficking associated with dengue blocking in wolbachia infected aedes aegypti cells |
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