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PLoS Pathog. 2018 Nov 13;14(11):e1007445. doi: 10.1371/journal.ppat.1007445. eCollection 2018 Nov.

Whole genome screen reveals a novel relationship between Wolbachia levels and Drosophila host translation.

Author information

1
Department of Cell Biology, Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, United States of America.
2
High Throughput Biology Core, Skirball Institute at New York University Langone Medical Center, New York, NY, United States of America.
3
Department of Genetics and Institute of Bioinformatics, University of Georgia, Athens, GA, United States of America.
4
Section of Developmental Genomics, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United States of America.

Abstract

Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts. Insects such as mosquitos act as vectors for many devastating human viruses such as Dengue, West Nile, and Zika. Remarkably, Wolbachia infection provides insect hosts with resistance to many arboviruses thereby rendering the insects ineffective as vectors. To utilize Wolbachia effectively as a tool against vector-borne viruses a better understanding of the host-Wolbachia relationship is needed. To investigate Wolbachia-insect interactions we used the Wolbachia/Drosophila model that provides a genetically tractable system for studying host-pathogen interactions. We coupled genome-wide RNAi screening with a novel high-throughput fluorescence in situ hybridization (FISH) assay to detect changes in Wolbachia levels in a Wolbachia-infected Drosophila cell line JW18. 1117 genes altered Wolbachia levels when knocked down by RNAi of which 329 genes increased and 788 genes decreased the level of Wolbachia. Validation of hits included in depth secondary screening using in vitro RNAi, Drosophila mutants, and Wolbachia-detection by DNA qPCR. A diverse set of host gene networks was identified to regulate Wolbachia levels and unexpectedly revealed that perturbations of host translation components such as the ribosome and translation initiation factors results in increased Wolbachia levels both in vitro using RNAi and in vivo using mutants and a chemical-based translation inhibition assay. This work provides evidence for Wolbachia-host translation interaction and strengthens our general understanding of the Wolbachia-host intracellular relationship.

PMID:
30422992
PMCID:
PMC6258568
DOI:
10.1371/journal.ppat.1007445
[Indexed for MEDLINE]
Free PMC Article

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