<i>Wolbachia</i> and Virus Alter the Host Transcriptome at the Interface of Nucleotide Metabolism Pathways

Abstract

<i>Wolbachia</i> is a maternally transmitted bacterium that manipulates arthropod and nematode biology in myriad ways. The <i>Wolbachia</i> strain colonizing <i>Drosophila melanogaster</i> creates sperm-egg incompatibilities and protects its host against RNA viruses, making it a promising tool for vector control. Despite successful trials using <i>Wolbachia</i>-transfected mosquitoes for dengue control, knowledge of how <i>Wolbachia</i> and viruses jointly affect insect biology remains limited. Using the <i>Drosophila melanogaster</i> model, transcriptomics and gene expression network analyses revealed pathways with altered expression and splicing due to <i>Wolbachia</i> colonization and virus infection. Included are metabolic pathways previously unknown to be important for <i>Wolbachia</i>-host interactions. Additionally, <i>Wolbachia</i>-colonized flies exhibit a dampened transcriptomic response to virus infection, consistent with early blocking of virus replication. Finally, using <i>Drosophila</i> genetics, we show that <i>Wolbachia</i> and expression of nucleotide metabolism genes have interactive effects on virus replication. Understanding the mechanisms of pathogen blocking will contribute to the effective development of <i>Wolbachia</i>-mediated vector control programs.<b>IMPORTANCE</b> Recently developed arbovirus control strategies leverage the symbiotic bacterium <i>Wolbachia</i>, which spreads in insect populations and blocks viruses from replicating. While this strategy has been successful, details of how this "pathogen blocking" works are limited. Here, we use a combination of virus infections, fly genetics, and transcriptomics to show that <i>Wolbachia</i> and virus interact at host nucleotide metabolism pathways.