The RNAi pathway plays a small part in Wolbachia-mediated blocking of dengue virus in mosquito cells

Terradas, Gerard; Joubert, D. Albert; McGraw, Elizabeth A.

doi:10.1038/srep43847

Cited by 68 publications

(73 citation statements)

References 85 publications

(123 reference statements)

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“…In addition to the Toll and IMD pathways, it is also worthwhile to explore the role of the JAK/STATB(Janus Kinase-Signal Transducer Activator of Transcription) and JNK (c-Jun N-terminal kinase) pathways in the Wolbachia –host symbiotic relationship in the future studies. Induction of the JAK/STAT pathway by w Mel has been reported in A. aegypti ( Terradas et al , 2017 ). Evidence also shows that the JAK/STAT pathway controls DENV infection in A. aegypti ( Souza-Neto et al , 2009 ) and West Nile virus infection in Culex mosquitoes ( Paradkar et al , 2012 ).…”

Section: Discussionmentioning

confidence: 90%

The bacterium Wolbachia exploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquito Aedes aegypti

et al. 2017

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A host’s immune system plays a central role in shaping the composition of the microbiota and, in return, resident microbes influence immune responses. Symbiotic associations of the maternally transmitted bacterium Wolbachia occur with a wide range of arthropods. It is, however, absent from the dengue and Zika vector mosquito Aedes aegypti in nature. When Wolbachia is artificially forced to form symbiosis with this new mosquito host, it boosts the basal immune response and enhances the mosquito’s resistance to pathogens, including dengue, Zika virus and malaria parasites. The mechanisms involved in establishing a symbiotic relationship between Wolbachia and A. aegypti, and the long-term outcomes of this interaction, are not well understood. Here, we have demonstrated that both the immune deficiency (IMD) and Toll pathways are activated by the Wolbachia strain wAlbB upon its introduction into A. aegypti. Silencing the Toll and IMD pathways via RNA interference reduces the wAlbB load. Notably, wAlbB induces peptidoglycan recognition protein (PGRP)-LE expression in the carcass of A. aegypti, and its silencing results in a reduction of symbiont load. Using transgenic mosquitoes with stage-specific induction of the IMD and Toll pathways, we have shown that elevated wAlbB infection in these mosquitoes is maintained via maternal transmission. These results indicate that host innate immunity is utilized to establish and promote host-microbial symbiosis. Our results will facilitate a long-term projection of the stability of the Wolbachia–A. aegypti mosquito system that is being developed to control dengue and Zika virus transmission to humans.

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Section: Discussionmentioning

confidence: 90%

The bacterium Wolbachia exploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquito Aedes aegypti

et al. 2017

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“…Wolbachia-mediated suppression of viral replication in hosts is well described [7,8,11,12,64]. Multiple mechanisms may underlie this observation including interference with viral entry and very early stages of viral replication [38,53,57,[64][65][66][67][68][69][70][71]. All viruses depend on host translation machinery for replication of their genomes.…”

Section: Discussionmentioning

confidence: 99%

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

Grobler

Yun

Kahler

et al. 2018

Preprint

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1Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts. 2Insects such as mosquitos act as vectors for many devastating human viruses such as 3 Dengue, West Nile, and Zika. Remarkably, Wolbachia infection provides insect hosts with 4 resistance to many arboviruses thereby rendering the insects ineffective as vectors. To 5 utilize Wolbachia effectively as a tool against vector-borne viruses a better understanding 6 of the host-Wolbachia relationship is needed. To investigate Wolbachia-insect 7 interactions we used the Wolbachia/Drosophila model that provides a genetically 8 tractable system for studying host-pathogen interactions. We coupled genome-wide RNAi 9 screening with a novel high-throughput fluorescence in situ hybridization (FISH) assay to 10 detect changes in Wolbachia levels in a Wolbachia-infected Drosophila cell line JW18. 11 1117 genes altered Wolbachia levels when knocked down by RNAi of which 329 genes 12 increased and 788 genes decreased the level of Wolbachia. Validation of hits included in 13 depth secondary screening using in vitro RNAi, Drosophila mutants, and Wolbachia-14 detection by DNA qPCR. A diverse set of host gene networks was identified to regulate 15 Wolbachia levels and unexpectedly revealed that perturbations of host translation 16 components such as the ribosome and translation initiation factors results in increased 17 Wolbachia levels both in vitro using RNAi and in vivo using mutants and a chemical-based 18 translation inhibition assay. This work provides evidence for Wolbachia-host translation 19 interaction and strengthens our general understanding of the Wolbachia-host intracellular 20 relationship. 21 22 23 Author summary 24Insects such as mosquitos act as vectors to spread devastating human diseases such as 25Dengue, West Nile, and Zika. It is critical to develop control strategies to prevent the 26 transmission of these diseases to human populations. A novel strategy takes advantage 27 of an endosymbiotic bacterium Wolbachia pipientis. The presence of this bacterium in 28 insect vectors prevents successful transmission of RNA viruses. The degree to which 29 viruses are blocked by Wolbachia is dependent on the levels of the bacteria present in 30 the host such that higher Wolbachia levels induce a stronger antiviral effect. In order to 31 use Wolbachia as a tool against vector-borne virus transmission a better understanding 32 of host influences on Wolbachia levels is needed. Here we performed a genome-wide 33RNAi screen in a model host system Drosophila melanogaster infected with Wolbachia 34 to identify host systems that affect Wolbachia levels. We found that host translation can 35influence Wolbachia levels in the host. 36 37 Wolbachia-host interactions can be studied in the genetically tractable Drosophila 63 melanogaster system which allows for the systematic dissection of host signaling 64 pathways that interact with the bacteria using the wide array of genetic and genomic tools 65 available. The Drosophila system enables rapid unbias...

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“…Induction of the JAK/ STAT pathway by wMel has been reported in A. aegypti (Terradas et al, 2017). Evidence also shows that the JAK/STAT pathway controls DENV infection in A. aegypti (Souza-Neto et al, 2009) and West Nile virus infection in Culex mosquitoes (Paradkar et al, 2012).…”

Section: Discussionmentioning

confidence: 94%

The bacteriumWolbachiaexploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquitoAedes aegypti

Pan¹

2016

2016 International Congress of Entomology

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A host's immune system plays a central role in shaping the composition of the microbiota and, in return, resident microbes influence immune responses. Symbiotic associations of the maternally transmitted bacterium Wolbachia occur with a wide range of arthropods. It is, however, absent from the dengue and Zika vector mosquito Aedes aegypti in nature. When Wolbachia is artificially forced to form symbiosis with this new mosquito host, it boosts the basal immune response and enhances the mosquito's resistance to pathogens, including dengue, Zika virus and malaria parasites. The mechanisms involved in establishing a symbiotic relationship between Wolbachia and A. aegypti, and the long-term outcomes of this interaction, are not well understood. Here, we have demonstrated that both the immune deficiency (IMD) and Toll pathways are activated by the Wolbachia strain wAlbB upon its introduction into A. aegypti. Silencing the Toll and IMD pathways via RNA interference reduces the wAlbB load. Notably, wAlbB induces peptidoglycan recognition protein (PGRP)-LE expression in the carcass of A. aegypti, and its silencing results in a reduction of symbiont load. Using transgenic mosquitoes with stage-specific induction of the IMD and Toll pathways, we have shown that elevated wAlbB infection in these mosquitoes is maintained via maternal transmission. These results indicate that host innate immunity is utilized to establish and promote host-microbial symbiosis. Our results will facilitate a long-term projection of the stability of the Wolbachia-A. aegypti mosquito system that is being developed to control dengue and Zika virus transmission to humans.

show abstract

The RNAi pathway plays a small part in Wolbachia-mediated blocking of dengue virus in mosquito cells

Cited by 68 publications

References 85 publications

The bacterium Wolbachia exploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquito Aedes aegypti

The bacterium Wolbachia exploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquito Aedes aegypti

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

The bacteriumWolbachiaexploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquitoAedes aegypti

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