Wolbachia is a maternally transmitted bacterium that manipulates arthropod and nematode biology in myriad ways. The Wolbachia strain colonizing Drosophila melanogaster creates sperm-egg incompatibilities and protects its host against RNA viruses, making it a promising tool for vector control. Despite successful trials using Wolbachia-transfected mosquitoes for dengue control, knowledge of how Wolbachia and viruses jointly affect insect biology remains limited. Using the Drosophila melanogaster model, transcriptomics and gene expression network analyses revealed pathways with altered expression and splicing due to Wolbachia colonization and virus infection. Included are metabolic pathways previously unknown to be important for Wolbachia-host interactions. Additionally, Wolbachia-colonized flies exhibit a dampened transcriptomic response to virus infection, consistent with early blocking of virus replica-tion. Finally, using Drosophila genetics, we show that Wolbachia 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 Wolbachia-mediated vector control programs. IMPORTANCE Recently developed arbovirus control strategies leverage the symbiotic bacterium Wolbachia, 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 genet-ics, and transcriptomics to show that Wolbachia and virus interact at host nucleotide metabolism pathways.
Bibliographical noteFunding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases (R21 AI121849 to I.L.G.N. and R.W.H., and R01AI144430 to I.L.G.N.). Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. Thank you to MaryAnn Martin, Audrey Parish, Delaney Miller, Lindsay Nevalainen, Danny Rice, and anonymous reviewers for comments on earlier drafts of the manuscript.
This work was supported by the National Institute of Allergy and Infectious Diseases (R21 AI121849 to I.L.G.N. and R.W.H., and R01AI144430 to I.L.G.N.). Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study.
© 2021 Lindsey et al.
- Drosophila melanogaster
- Host response
- Pathogen blocking
- Sindbis virus