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Wolbachia-mediated antiviral protection is driven by its multimodal effects on Drosophila melanogaster metabolism

Created on 24 Oct 2025

Authors

Walsh, S. M., Thomson, T. G., Johnson, K. N., Brownlie, J. C., Schirra, H. J.

Abstract

Wolbachia, a common endosymbiont of Drosophila melanogaster, provides a profound antiviral effect in insects. Wolbachia-mediated viral interference has been employed to limit the spread of arboviruses, including dengue. However, the mechanisms underpinning Wolbachia-mediated viral interference are not consistently understood. Previous studies have identified resource competition as a potential mechanism by which Wolbachia disrupts viral replication. Our study uses nuclear magnetic resonance (NMR)-based metabolomics to characterize the bi- and tripartite host-Wolbachia-virus interactions using the model insect Drosophila melanogaster, the protective Wolbachia strain wMel and the pathogenic Drosophila C virus (DCV). The findings reveal that wMel-infected flies showed increased simple carbohydrate catabolism relative to uninfected Drosophila. DCV infection perturbed nucleotide synthesis and nucleotide abundance in Drosophila compared to uninfected Drosophila, driving metabolism to likely meet the viral replication demands imposed on the host. Notably, co-infected Drosophila exhibited a metabolic profile more similar to wMel-infected flies than DCV-infected flies, suggesting that wMel drives metabolism in a direction that at least temporarily inhibits DCV replication. The metabolic profile is indicative of a hypoxic environment that has been known to trigger immune pathways that further contribute to Wolbachia-mediated pathogen blocking. It is probable that Wolbachia-mediated antiviral protection is a multimodal consequence of wMel's influence on host metabolism, rather than a single mechanism. These findings will guide future research and contribute to the continued success of Wolbachia-based vector control strategies against RNA arboviruses, potentially leading to novel approaches for defending against such pathogens and improving vector control strategies.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Oct 2025.

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