Differences in proteome perturbations caused by the Wolbachia strain wAu suggest multiple mechanisms of Wolbachia-mediated antiviral activity

Rainey, S. M., Geoghegan, V., Lefteri, D. A. , Ant, T. H., Martinez, J. , McNamara, C. J., Kamel, W. , de Laurent, Z. R., Castello, A. and Sinkins, S. P. (2023) Differences in proteome perturbations caused by the Wolbachia strain wAu suggest multiple mechanisms of Wolbachia-mediated antiviral activity. Scientific Reports, 13, 11737. (doi: 10.1038/s41598-023-38127-4) (PMID:37474590) (PMCID:PMC10359319)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Castello, Professor Alfredo and Rainey, Dr Stephanie and Laurent, Zaydah Rolande De and Ant, Dr Thomas and McNamara, Cameron and Kamel, Dr Wael and Geoghegan, Vincent and Martinez, Dr Julien and Sinkins, Professor Steven and Lefteri, Dr Daniella
Authors: Rainey, S. M., Geoghegan, V., Lefteri, D. A., Ant, T. H., Martinez, J., McNamara, C. J., Kamel, W., de Laurent, Z. R., Castello, A., and Sinkins, S. P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Scientific Reports 13: 11737
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.1452

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173477Wolbachia-mediated arbovirus inhibition in mosquitoesSteven SinkinsWellcome Trust (WELLCOTR)202888/Z/16/ZSII - MRC-UofG Centre for Virus Research
174018Wolbachia-based control of virus transmission by the mosquito Aedes albopictusSteven SinkinsWellcome Trust (WELLCOTR)108508/A/15/ZSII - MRC-UofG Centre for Virus Research