A Wolbachia pipientis protein confers resistance to virus infection in Drosophila melanogaster
- 1Max-Planck Institute for Biology of Ageing, Germany; Institute of Healthy Ageing, and GEE, UCL, United Kingdom
Abstract
The intracellular bacterium Wolbachia pipientis alters the biology of its arthropod hosts in many ways, and can increase resistance to RNA viruses in both Drosophila and mosquitoes. Wolbachia-induced pathogen blocking has generated much interest because of its potential to restrict insect vector transmission of human diseases caused by RNA viruses. However, the molecular mechanisms by which Wolbachia affects host viral resistance are still mostly elusive. We used dilp2-3,5 mutant Drosophila, which are long-lived, but only in the presence of Wolbachia, to show that the presence of Wolbachia also increased the resistance of the mutant flies to infection with Drosophila C virus (DCV), relative both to mutants lacking Wolbachia and to wild type flies with and without Wolbachia. The insulin mutant flies had higher Wolbachia titres than wild type flies. By RNA-seq analysis of the Wolbachia transcriptome, we identified Wolbachia genes that were more strongly expressed in dilp2-3,5 mutant flies. Ankyrin-domain-containing proteins were among the most strongly up-regulated and they are predicted to be secreted effector proteins. To address their effect on host physiology, we generated 4 transgenic fly lines each with inducible expression of a different genes encoding ankyrin-domain-containing proteins. Expression of 3 of these did not cause obvious effects, but expression of WD0754 at high levels severely shortened fly survival. Interestingly, however, chronic low-level induction of WD0754 increased the resistance of the flies to DCV infection. Proteomics analysis showed a robust, tissue-specific, anti-viral response upon WD0754 induction, and identified the NFkB-like IMD pathway as a potential mediator of the antiviral activity of WD0754. Consistently, WD0754 expression activated Relish, a key downstream transcriptional mediator of IMD signalling, while loss-of Relish blocked the antiviral effect of WD0754. In summary, we identified a Wolbachia-derived ankyrin domain containing protein that modulates host immunity through the IMD pathway.
Related
- Harnessing variation in Drosophila melanogaster reveals different routes to increased infection susceptibility over age and sex-dependent association with lifespan
- Wild ginseng adventitious roots restore sleep homeostasis in sleep-deprived Drosophila melanogaster
- Drosophila CerS homeodomain sites differentially alter insulin resistance
- Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection
- Wolbachia outcompetes mosquito-borne viruses by reprogramming host ATPSβ1-driven ATP metabolism toward symbiotic proliferation
BibTeX
@misc{leech2026wolbachia,
title = {{A Wolbachia pipientis protein confers resistance to virus infection in Drosophila melanogaster}},
author = {T. Leech and B. Taschke and R. L. Meilenbrock and L. Tain and P. Zhang and S. Gronke and L. Partridge},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753151},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753151v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Wolbachia pipientis protein confers resistance to virus infection in Drosophila melanogaster
AU - T. Leech
AU - B. Taschke
AU - R. L. Meilenbrock
AU - L. Tain
AU - P. Zhang
AU - S. Gronke
AU - L. Partridge
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753151
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753151v1
AB - The intracellular bacterium Wolbachia pipientis alters the biology of its arthropod hosts in many ways, and can increase resistance to RNA viruses in both Drosophila and mosquitoes. Wolbachia-induced pathogen blocking has generated much interest because of its potential to restrict insect vector transmission of human diseases caused by RNA viruses. However, the molecular mechanisms by which Wolbachia affects host viral resistance are still mostly elusive. We used dilp2-3,5 mutant Drosophila, which are long-lived, but only in the presence of Wolbachia, to show that the presence of Wolbachia also increased the resistance of the mutant flies to infection with Drosophila C virus (DCV), relative both to mutants lacking Wolbachia and to wild type flies with and without Wolbachia. The insulin mutant flies had higher Wolbachia titres than wild type flies. By RNA-seq analysis of the Wolbachia transcriptome, we identified Wolbachia genes that were more strongly expressed in dilp2-3,5 mutant flies. Ankyrin-domain-containing proteins were among the most strongly up-regulated and they are predicted to be secreted effector proteins. To address their effect on host physiology, we generated 4 transgenic fly lines each with inducible expression of a different genes encoding ankyrin-domain-containing proteins. Expression of 3 of these did not cause obvious effects, but expression of WD0754 at high levels severely shortened fly survival. Interestingly, however, chronic low-level induction of WD0754 increased the resistance of the flies to DCV infection. Proteomics analysis showed a robust, tissue-specific, anti-viral response upon WD0754 induction, and identified the NFkB-like IMD pathway as a potential mediator of the antiviral activity of WD0754. Consistently, WD0754 expression activated Relish, a key downstream transcriptional mediator of IMD signalling, while loss-of Relish blocked the antiviral effect of WD0754. In summary, we identified a Wolbachia-derived ankyrin domain containing protein that modulates host immunity through the IMD pathway.
ER -