Differences in proteome perturbations caused by the Wolbachia strain wAu suggest multiple mechanisms of Wolbachia-mediated antiviral activity.
Differences in proteome perturbations caused by the Wolbachia strain wAu suggest multiple mechanisms of Wolbachia-mediated antiviral activity.
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DOI：
10.1038/s41598-023-38127-4
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发表时间：
2023-07-20
影响因子：
4.6
通讯作者：
Sinkins, Steven P.
中科院分区：
文献类型：
--
作者：
Rainey, Stephanie M.;Geoghegan, Vincent;Lefteri, Daniella A.;Ant, Thomas H.;Martinez, Julien;McNamara, Cameron J.;Kamel, Wael;de Laurent, Zaydah Rolande;Castello, Alfredo;Sinkins, Steven P.
遗传沃尔巴克氏菌的一些菌株已被证明在实验室和现场环境中可有效减少埃及伊蚊传播登革热病毒（DENV）和其他RNA病毒，目前正在用于登革热病毒控制。不同沃尔巴克氏体菌株对病毒的抑制程度不同。密度和组织趋向性可能导致这些差异，但也有迹象表明这不是唯一的因素：例如，菌株wAu和wAlbA保持在相似的细胞内密度，但只有wAu产生强烈的DENV抑制作用。我们之前报道了脂质转运动力学的扰动，包括脂滴中胆固醇的固存，菌株wMel/wMelPop在Ae中。蚊。为了进一步研究这些差异背后的细胞基础，我们对伊蚊的中肠进行了蛋白质组学分析。携带wAu和wAlbA菌株的埃及伊蚊系：假设扰动的差异可能强调沃尔巴克氏体介导的抗病毒活性。令人惊讶的是，与未携带沃尔巴克氏体和携带沃尔巴克氏体的肠道相比，携带沃尔巴克氏体的肠道不仅表现出明显的蛋白质组紊乱，而且携带沃尔巴克氏体的肠道也表现出明显的蛋白质组紊乱。在携带ww的细胞系中，存在RNA加工途径的改变和一组特定RNA结合蛋白的上调，包括已知具有抗病毒活性的基因。菌株之间的脂质转运和代谢蛋白质组变化也不同，我们发现菌株wAu不产生与wMel相同的胆固醇隔离表型。此外，与wMel相比，环糊精治疗并没有恢复wAu的抗病毒活性。总之，这些结果表明，与以前表征的沃尔巴克氏菌菌株相比，wAu可能在抑制虫媒病毒方面表现出独特的特征。
Some strains of the inherited bacterium Wolbachia have been shown to be effective at reducing the transmission of dengue virus (DENV) and other RNA viruses by Aedes aegypti in both laboratory and field settings and are being deployed for DENV control. The degree of virus inhibition varies between Wolbachia strains. Density and tissue tropism can contribute to these differences but there are also indications that this is not the only factor involved: for example, strains wAu and wAlbA are maintained at similar intracellular densities but only wAu produces strong DENV inhibition. We previously reported perturbations in lipid transport dynamics, including sequestration of cholesterol in lipid droplets, with strains wMel/wMelPop in Ae. aegypti. To further investigate the cellular basis underlying these differences, proteomic analysis of midguts was carried out on Ae. aegypti lines carrying strains wAu and wAlbA: with the hypothesis that differences in perturbations may underline Wolbachia-mediated antiviral activity. Surprisingly, wAu-carrying midguts not only showed distinct proteome perturbations when compared to non-Wolbachia carrying and wAlbA-carrying midguts but also wMel-carrying midguts. There are changes in RNA processing pathways and upregulation of a specific set of RNA-binding proteins in the wAu-carrying line, including genes with known antiviral activity. Lipid transport and metabolism proteome changes also differ between strains, and we show that strain wAu does not produce the same cholesterol sequestration phenotype as wMel. Moreover, in contrast to wMel, wAu antiviral activity was not rescued by cyclodextrin treatment. Together these results suggest that wAu could show unique features in its inhibition of arboviruses compared to previously characterized Wolbachia strains.
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影响因子：
16.6
作者：
Gestuveo RJ;Royle J;Donald CL;Lamont DJ;Hutchinson EC;Merits A;Kohl A;Varjak M
通讯作者：
Varjak M
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影响因子：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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