Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells.
Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells.
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DOI：
10.1038/s41467-017-00610-8
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发表时间：
2017-09-13
影响因子：
16.6
通讯作者：
Sinkins SP
中科院分区：
文献类型：
--
作者：
Geoghegan V;Stainton K;Rainey SM;Ant TH;Dowle AA;Larson T;Hester S;Charles PD;Thomas B;Sinkins SP
沃尔巴克氏体是细胞内母系遗传的细菌，可以通过昆虫种群传播并阻断蚊子传播病毒，为登革热控制提供了重要方法。为了更好地了解病毒抑制的机制，我们在这里进行蛋白质组定量的影响，沃尔巴克氏体在埃及伊蚊蚊子细胞和中肠。在囊泡运输、脂质代谢和内质网中观察到可能影响病毒进入和复制的扰动。沃尔巴克氏体感染的细胞显示出不同的胆固醇谱，包括酯化胆固醇水平升高，这与受干扰的细胞内胆固醇运输一致。环糊精已被证明可以逆转胆固醇稳态被破坏的细胞中的脂质积累缺陷。沃尔巴克氏体感染的Ae.用2-羟丙基-β-环糊精处理埃及伊蚊细胞恢复了携带沃尔巴克氏体的细胞中的登革热复制，表明登革热在沃尔巴克氏体感染的细胞中通过局部胆固醇积累而受到抑制。这些结果表明，细胞沃尔巴克氏体病毒抑制表型和脂质储存遗传疾病之间的相似之处。 沃尔巴克氏体感染蚊子可以阻断登革热病毒的感染，并在现场试验中进行了测试，但作用机制尚不清楚。Geoghegan等人使用蛋白质组学，在这里确定了Wolbachia对埃及伊蚊胆固醇稳态和登革病毒复制的影响。
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. Wolbachia infection of mosquitoes can block dengue virus infection and is tested in field trials, but the mechanism of action is unclear. Using proteomics, Geoghegan et al. here identify effects of Wolbachia on cholesterol homeostasis and dengue virus replication in Aedes aegypti.
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影响因子：
3.8
作者：
Frentiu FD;Zakir T;Walker T;Popovici J;Pyke AT;van den Hurk A;McGraw EA;O'Neill SL
通讯作者：
O'Neill SL
影响因子：
5.4
作者：
Li, Qi;Liu, Zhiguo;Qu, Shen
通讯作者：
Qu, Shen
影响因子：
3.8
作者：
Hoffmann AA;Iturbe-Ormaetxe I;Callahan AG;Phillips BL;Billington K;Axford JK;Montgomery B;Turley AP;O'Neill SL
通讯作者：
O'Neill SL
影响因子：
6.7
作者：
Caragata EP;Rancès E;Hedges LM;Gofton AW;Johnson KN;O'Neill SL;McGraw EA
通讯作者：
McGraw EA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y