Wolbachia endosymbionts in Drosophila regulate the resistance to Zika virus infection in a sex dependent manner

Drosophila melanogaster has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity and virus-induced pathology. Previous studies have shown that the presence of Wolbachia endosymbionts in D. melanogaster confers resistance to infection by certain viral pathogens. Zika virus is an important vector-borne pathogen that has recently expanded its range due to the wide geographical distribution of the mosquito vector. Here, we describe the effect of Wolbachia on the immune response of D. melanogaster adult flies following Zika virus infection. First, we show that the presence of Wolbachia endosymbionts promotes the longevity of uninfected D. melanogaster wild type adults and increases the survival response of flies following Zika virus injection. We find that the latter effect is more pronounced in females rather than in males. Then, we show that the presence of Wolbachia regulates Zika virus replication during Zika virus infection of female flies. In addition, we demonstrate that the antimicrobial peptide-encoding gene Drosocin and the sole Jun N-terminal kinase-specific MAPK phosphatase Puckered are upregulated in female adult flies, whereas the immune and stress response gene TotM is upregulated in male individuals. Finally, we find that the activity of RNA interference and Toll signaling remain unaffected in Zika virus-infected female and male adults containing Wolbachia compared to flies lacking the endosymbionts. Our results reveal that Wolbachia endosymbionts in D. melanogaster affect innate immune signaling activity in a sex-specific manner, which in turn influences host resistance to Zika virus infection. This information contributes to a better understanding of the complex interrelationship between insects, their endosymbiotic bacteria, and viral infection. Interpreting these processes will help us design more effective approaches for controlling insect vectors of infectious disease

Pathologies tissu spécifiques induites par deux virus à ARN chez la Drosophile

Les insectes sont exposés dans leur environnement à de nombreux virus, et ces infections peuvent avoir un impact économique ou médical. Peu de choses sont connues sur les mécanismes physiopathologiques impliqués dans la susceptibilité aux infections viralInsects are exposed in their environement to many viruses, and these infections can have a significant economic or medical impact. At present, little is known about the pathophysiological mechanisms involved in susceptibility to viral infections. We use

Pathologies tissu spécifiques induites par deux virus à ARN chez la Drosophile

Les insectes sont exposés dans leur environnement à de nombreux virus, et ces infections peuvent avoir un impact économique ou médical. Peu de choses sont connues sur les mécanismes physiopathologiques impliqués dans la susceptibilité aux infections virales. Nous avons utilisé l'organisme modèle drosophile pour étudier la pathologie induite par deux virus à ARN: le virus C de la drosophile (DCV) et le Flock House virus (FHV). La comparaison du transcriptome de mouches infectées par ces deux virus montre que l'infection par le DCV conduit à la forte répression de plusieurs centaines de gènes, principalement exprimés dans l'intestin moyen des mouches. Parmi eux, plusieurs sont également réprimés dans des conditions jeûne, ce qui suggère que les mouches infectées cessent de se nourrir. Cependant, les mouches infectées par les DCV continuent à se nourrir et leur poids augmente. Cela est dû à une excrétion diminuée, associée à une obstruction dans l'intestin moyen de la mouche. La pathologie induite par le DCV est due à la présence du virus dans un tissu particulier, plutôt que de l'effet néfaste de la réponse immunitaire de l'hôte. Nous avons identifié le gène dSUR, codant la sous-unité d'un canal potassium ATP dépendant (KATP). dSUR est exprimé dans le cœur des mouches, et les mutants pour ce gène sont plus sensibles à l'infection par le FHV et contiennent des charges virales plus élevées que les témoins. Nous avons montré que FHV est cardiotropique et que l'activité des KATP cardiaques est liée au mécanisme antiviral de l'interférence ARN. Nous montrons que DCV et FHV, qui semblent très similaires à première vue, induisent des pathologies très différentes chez la drosophile.Insects are exposed in their environement to many viruses, and these infections can have a significant economic or medical impact. At present, little is known about the pathophysiological mechanisms involved in susceptibility to viral infections. We used the model organism Drosophila melanogaster to study the pathology induced by two RNA viruses: the Drosophila C virus (DCV) and the Flock House Virus (FHV).We compared the transcriptome of DCV and FHV-infected flies by using genome-wide microarrays. DCV infection leads to the strong repression of several hundred of genes, mainly expressed in the midgut of the fly. Many genes repressed by the DCV are also repressed under conditions of starvation, suggesting that infected flies stop feeding. However, DCV-infected flies continue to feed and gain weight until their death. This is due to decreased excretion, associated with an intestinal obstruction in the anterior midgut of the fly that probably occurs at the level of the cardia. The pathology induced by DCV results from the presence of the virus in a particular tissue, rather than from the adverse effect of the host s immune response. On the other hand, we identified the gene dSUR, which encode the subunit of an ATP-dependent potassium channel (KATP). dSUR is expressed in the Drosophila heart and mutants for this gene are more sensitive to FHV and contain higher viral loads than controls. We showed that FHV is cardiotropic virus and that the cardiac KATP activity is related to the major antiviral mechanism RNA interference. Our work shows that DCV and FHV, which appear very similar at first sight, induce very different, organ-specific pathologies in Drosophila

Tissue-specific pathologies induced by two RNA viruses in drosophila melanogaster

Les insectes sont exposés dans leur environement à de nombreux virus, et ces infections peuvent avoir un impact économique ou médical. Peu de choses sont connues sur les mécanismes physiopathologiques impliqués dans la susceptibilité aux infections virales. Nous avons utilisé l'organisme modèle drosophile pour étudier la pathologie induite par deux virus à ARN: le virus C de la drosophile (DCV) et le Flock House virus (FHV). La comparaison du transcriptome de mouches infectées par ces deux virus montre que l’infection par le DCV conduit à la forte répression de plusieurs centaines de gènes, principalement exprimés dans l’intestin moyen des mouches. Parmi eux, plusieurs sont également réprimés dans des conditions jeûne, ce qui suggère que les mouches infectées cessent de se nourrir. Cependant, les mouches infectées par les DCV continuent à se nourrir et leur poids augmente. Cela est dû à une excrétion diminuée, associée à une obstruction dans l'intestin moyen de la mouche. La pathologie induite par le DCV est due à la présence du virus dans un tissu particulier, plutôt que de l'effet néfaste de la réponse immunitaire de l'hôte. Nous avons identifié le gène dSUR, codant la sous-unité d'un canal potassium ATP dépendant (KATP). dSUR est exprimé dans le cœur des mouches, et les mutants pour ce gène sont plus sensibles à l’infection par le FHV et contiennent des charges virales plus élevées que les témoins. Nous avons montré que FHV est cardiotropique et que l'activité des KATP cardiaques est liée au mécanisme antiviral de l'interférence ARN. Nous montrons que DCV et FHV, qui semblent très similaires à première vue, induisent des pathologies très différentes chez la drosophile.Insects are exposed in their environement to many viruses, and these infections can have a significant economic or medical impact. At present, little is known about the pathophysiological mechanisms involved in susceptibility to viral infections. We used the model organism Drosophila melanogaster to study the pathology induced by two RNA viruses: the Drosophila C virus (DCV) and the Flock House Virus (FHV). We compared the transcriptome of DCV and FHV-infected flies by using genome-wide microarrays. DCV infection leads to the strong repression of several hundred of genes, mainly expressed in the midgut of the fly. Many genes repressed by the DCV are also repressed under conditions of starvation, suggesting that infected flies stop feeding. However, DCV-infected flies continue to feed and gain weight until their death. This is due to decreased excretion, associated with an intestinal obstruction in the anterior midgut of the fly that probably occurs at the level of the cardia. The pathology induced by DCV results from the presence of the virus in a particular tissue, rather than from the adverse effect of the host’s immune response. On the other hand, we identified the gene dSUR, which encode the subunit of an ATP-dependent potassium channel (KATP). dSUR is expressed in the Drosophila heart and mutants for this gene are more sensitive to FHV and contain higher viral loads than controls. We showed that FHV is cardiotropic virus and that the cardiac KATP activity is related to the major antiviral mechanism RNA interference. Our work shows that DCV and FHV, which appear very similar at first sight, induce very different, organ-specific pathologies in Drosophila

Pathologies tissu spécifiques induites par deux virus à ARN chez la Drosophile

Les insectes sont exposés dans leur environnement à de nombreux virus, et ces infections peuvent avoir un impact économique ou médical. Peu de choses sont connues sur les mécanismes physiopathologiques impliqués dans la susceptibilité aux infections virales. Nous avons utilisé l'organisme modèle drosophile pour étudier la pathologie induite par deux virus à ARN: le virus C de la drosophile (DCV) et le Flock House virus (FHV). La comparaison du transcriptome de mouches infectées par ces deux virus montre que l infection par le DCV conduit à la forte répression de plusieurs centaines de gènes, principalement exprimés dans l intestin moyen des mouches. Parmi eux, plusieurs sont également réprimés dans des conditions jeûne, ce qui suggère que les mouches infectées cessent de se nourrir. Cependant, les mouches infectées par les DCV continuent à se nourrir et leur poids augmente. Cela est dû à une excrétion diminuée, associée à une obstruction dans l'intestin moyen de la mouche. La pathologie induite par le DCV est due à la présence du virus dans un tissu particulier, plutôt que de l'effet néfaste de la réponse immunitaire de l'hôte. Nous avons identifié le gène dSUR, codant la sous-unité d'un canal potassium ATP dépendant (KATP). dSUR est exprimé dans le cœur des mouches, et les mutants pour ce gène sont plus sensibles à l infection par le FHV et contiennent des charges virales plus élevées que les témoins. Nous avons montré que FHV est cardiotropique et que l'activité des KATP cardiaques est liée au mécanisme antiviral de l'interférence ARN. Nous montrons que DCV et FHV, qui semblent très similaires à première vue, induisent des pathologies très différentes chez la drosophile.Insects are exposed in their environement to many viruses, and these infections can have a significant economic or medical impact. At present, little is known about the pathophysiological mechanisms involved in susceptibility to viral infections. We used the model organism Drosophila melanogaster to study the pathology induced by two RNA viruses: the Drosophila C virus (DCV) and the Flock House Virus (FHV).We compared the transcriptome of DCV and FHV-infected flies by using genome-wide microarrays. DCV infection leads to the strong repression of several hundred of genes, mainly expressed in the midgut of the fly. Many genes repressed by the DCV are also repressed under conditions of starvation, suggesting that infected flies stop feeding. However, DCV-infected flies continue to feed and gain weight until their death. This is due to decreased excretion, associated with an intestinal obstruction in the anterior midgut of the fly that probably occurs at the level of the cardia. The pathology induced by DCV results from the presence of the virus in a particular tissue, rather than from the adverse effect of the host s immune response. On the other hand, we identified the gene dSUR, which encode the subunit of an ATP-dependent potassium channel (KATP). dSUR is expressed in the Drosophila heart and mutants for this gene are more sensitive to FHV and contain higher viral loads than controls. We showed that FHV is cardiotropic virus and that the cardiac KATP activity is related to the major antiviral mechanism RNA interference. Our work shows that DCV and FHV, which appear very similar at first sight, induce very different, organ-specific pathologies in Drosophila.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Role of Glial Immunity in Lifespan Determination: A Drosophila Perspective

Increasing body of evidence indicates that proper glial function plays an important role in neuroprotection and in organismal physiology throughout lifespan. Work done in the model organism Drosophila melanogaster has revealed important aspects of glial cell biology in the contexts of longevity and neurodegeneration. In this mini review, we summarize recent findings from work done in the fruit fly Drosophila about the role of glia in maintaining a healthy status during animal’s life and discuss the involvement of glial innate immune pathways in lifespan and neurodegeneration. Overactive nuclear factor kappa B (NF-κB) pathways and defective phagocytosis appear to be major contributors to lifespan shortening and neuropathology. Glial NF-κB silencing on the other hand, extends lifespan possibly through an immune–neuroendocrine axis. Given the evolutionary conservation of NF-κB innate immune signaling and of macrophage ontogeny across fruit flies, rodents, and humans, the above observations in glia could potentially support efforts for therapeutic interventions targeting to ameliorate age-related pathologies

<i>Drosophila</i> as a Model to Study Brain Innate Immunity in Health and Disease

Innate immunity is the first line of defense against invading pathogens and plays an essential role in defending the brain against infection, injury, and disease. It is currently well recognized that central nervous system (CNS) infections can result in long-lasting neurological sequelae and that innate immune and inflammatory reactions are highly implicated in the pathogenesis of neurodegeneration. Due to the conservation of the mechanisms that govern neural development and innate immune activation from flies to mammals, the lack of a classical adaptive immune system and the availability of numerous genetic and genomic tools, the fruit fly Drosophila melanogaster presents opportunities to investigate the cellular and molecular mechanisms associated with immune function in brain tissue and how they relate to infection, injury and neurodegenerative diseases. Here, we present an overview of currently identified innate immune mechanisms specific to the adult Drosophila brain

The role of micro RNAs (miRNAs) in the regulation of Drosophila melanogaster’s innate immunity

MicroRNAs (miRNAs) are a class of small non-coding RNAs ~19–22 nt long which post-transcriptionally regulate gene expression. Their ability to exhibit dynamic expression patterns coupled with their wide variety of targets allows miRNAs to regulate many processes, including the innate immune response of Drosophila melanogaster. Recent studies have identified miRNAs in Drosophila which are differentially expressed during infection with different pathogens as well as miRNAs that may affect immune signalling when differentially expressed. This review provides an overview of miRNAswhich have been identified to play a role in the immune response of Drosophila through targeting of the Toll and IMD signalling pathways and other immune processes. It will also explore the role of miRNAs in fine-tuning the immune response in Drosophila and highlight current gaps in knowledge regarding the role of miRNAs in immunity and areas for further research