Abstract

ABSTRACTCertain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue virus (DENV) by Aedes mosquitoes, and the mechanisms responsible are still not well understood. Direct infusion and liquid chromatography-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry-based lipidomics analyses were conducted using Aedes albopictus Aa23 cells that were infected with the wMel and wMelPop strains of Wolbachia in comparison to uninfected Aa23-T cells. Substantial shifts in the cellular lipid profile were apparent in the presence of Wolbachia. Most significantly, almost all sphingolipid classes were depleted, and some reductions in diacylglycerols and phosphatidylcholines were also observed. These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting that Wolbachia may produce a cellular lipid environment that is antagonistic to viral replication. The data improve our understanding of the intracellular interactions between Wolbachia and mosquitoes.IMPORTANCE Mosquitoes transmit a variety of important viruses to humans, such as dengue virus and Zika virus. Certain strains of the intracellular bacterial genus called Wolbachia found in or introduced into mosquitoes can block the transmission of viruses, including dengue virus, but the mechanisms responsible are not well understood. We found substantial shifts in the cellular lipid profiles in the presence of these bacteria. Some lipid classes previously shown to be enriched in dengue virus-infected mosquito cells were depleted in the presence of Wolbachia, suggesting that Wolbachia may produce a cellular lipid environment that inhibits mosquito-borne viruses.

Highlights

  • Certain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue virus (DENV) by Aedes mosquitoes, and the mechanisms responsible are still not well understood

  • Negative-ion direct infusion mass spectrometry (DIMS) analysis of the lipid extracts resulted in 2,044 peaks, which clustered into distinct lipid profiles for the three groups, distinguished by Principal-component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA)

  • PLS-DA results showed that Aa23.wMelPop was separated from the other lines along latent variable 1 (LV1), while separation between Aa23-T and Aa23.wMel was mostly along LV2 and, to a lesser extent, LV1 (Fig. 1B)

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Summary

Introduction

Certain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue virus (DENV) by Aedes mosquitoes, and the mechanisms responsible are still not well understood. Almost all sphingolipid classes were depleted, and some reductions in diacylglycerols and phosphatidylcholines were observed These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting that Wolbachia may produce a cellular lipid environment that is antagonistic to viral replication. Some lipid classes previously shown to be enriched in dengue virus-infected mosquito cells were depleted in the presence of Wolbachia, suggesting that Wolbachia may produce a cellular lipid environment that inhibits mosquito-borne viruses. In certain host-strain combinations, in particular where high bacterial densities are reached, Wolbachia can significantly reduce the transmission of some of the most important mosquito-borne pathogens of humans, including dengue (DENV) and Chikungunya viruses and malaria and filarial nematode parasites [2,3,4,5,6,7,8,9,10].

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