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The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila

ABSTRACT: The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate NF-kB family members. We have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways, and triggered activation of a STAT binding activity. Genetic experiments showed that the JAK kinase Hopscotch was involved in the control of the viral load in infected flies, and was required, though not sufficient, for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third evolutionary conserved innate immunity pathway operates in drosophila and counters viral infection. Keywords: JAK/STAT virus drosophila immunity

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE2828 | GEO | 2005/08/08

SECONDARY ACCESSION(S): PRJNA92453

REPOSITORIES: GEO

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Transcription profiling of Drosophila infected with Drosophila C virus reveals a third evolutionary conserved innate immunity pathway operates in drosophila and counters viral infection

Project description:The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate NF-kB family members. We have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways, and triggered activation of a STAT binding activity. Genetic experiments showed that the JAK kinase Hopscotch was involved in the control of the viral load in infected flies, and was required, though not sufficient, for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third evolutionary conserved innate immunity pathway operates in drosophila and counters viral infection.

2007-07-07 | E-GEOD-2828 | biostudies-arrayexpress

Expression profile of adult Drosophila melanogaster expressing a self-replicating RNA of Sindbis virus

Project description:Alphaviruses establish a persistent infection in arthropod vectors, which is essential for effective transmission of the virus to vertebrate hosts. The development of persistence in insects is not well understood, although it is thought to involve the innate immune response. Using a transgenic fly system (SINrep) expressing a self-replicating viral genome, we have previously demonstrated the antiviral response of the Drosophila Imd (Immune Deficiency) and Jak-STAT innate immunity pathways. In the current study, microarray analysis of SINrep flies in comparison to control GFP flies aims to detect genes that are sensitive to Sindbis viral RNA replication. Both SINrep and GFP adult flies were harvested 3 days post eclosion for RNA extraction and hybridization on Affymetrix microarrays. We look for genes significantly altered in the presence of viral RNA replication.

2013-01-31 | E-GEOD-42726 | biostudies-arrayexpress

Expression profile of adult Drosophila melanogaster expressing a self-replicating RNA of Sindbis virus

2013-01-31 | GSE42726 | GEO

A Dicistrovirus-specific inducible antiviral response in Drosophila

Project description:The fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity, and has led to some important discoveries on the sensing and signalling of microbial infections. The response of drosophila to virus infections remains poorly characterized, and appears to involve two facets. On one hand RNA interference (RNAi) involves the recognition and processing of dsRNA into small interfering (si) RNAs by the host ribonuclease Dicer-2 (Dcr-2), whereas on the other hand an inducible response controlled by the evolutionarily conserved JAK/STAT pathway contributes to the antiviral host defence. In order to clarify the contribution of the siRNA and JAK/STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type or mutant for Dcr-2 or the JAK kinase Hopscotch (Hop) to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by DCV and CrPV, two members of the Dicistroviridae family. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by DCV (GSE2828) or two unrelated RNA viruses, FHV and SINV. Overall, our data reveal that RNAi is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK/STAT pathway appears to be virus-specific. For each experimental challenge (FHV, 48 or 72 hours after infection; SINV, 4 or 8 days after infection), three biologically independent samples composed of 45 male Oregon R flies were used. Infection has been performed by injecting viral stocks prepared in Tris solution. Injection of the same volume of Tris has been used as control. Infected flies were then incubated for 48 or 72 hours in the case of FHV and 4 days or 8 days in the case of SINV.

2013-02-06 | E-GEOD-31542 | biostudies-arrayexpress

The transcriptional response of Drosophila melanogaster to infection with the sigma virus (Rhabdoviridae)

Project description:Bacterial and fungal infections induce a potent immune response in Drosophila melanogaster, but it is unclear whether viral infections induce a similar immune response. Using microarrays, we examined the changes in gene expression in Drosophila that occur in response to infection with the sigma virus, a negative-stranded RNA virus (Rhabdoviridae) that occurs in wild populations of D. melanogaster. We detected many changes in gene expression in infected flies, but found no evidence for the activation of the Toll, IMD or Jak-STAT pathways, which control immune responses against other pathogens. We identified a number of functional categories of genes, including serine proteases, ribosomal proteins and chorion proteins that were overrepresented among the differentially expressed genes. We also found that the sigma virus alters the expression of many more genes in males than in females. In contrast to previous results, our data suggest that either Drosophila do not mount an immune response against the sigma virus, or that the immune response is not controlled by known immune pathways. The genes which we identified as differentially expressed after infection are promising candidates for controlling the host’s response to the sigma virus.

2009-09-11 | GSE17377 | GEO

A Dicistrovirus-specific inducible antiviral response in Drosophila

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The cytokine DIEDEL and a viral homologue suppress deleterious IMD-dependent gene expression in drosophila

Project description:Viral infection in Drosophila triggers inducible gene expression, but the function of many of these genes and the biological significance of their induction remain poorly understood. Here, we report the functional characterization of the gene Diedel, which is strongly induced following some viral infections and encodes a 12kDa circulating protein. Diedel mutant flies have reduced viability and succumb rapidly to infection with Sindbis virus. This phenotype is associated with deregulated expression of IMD target genes and is rescued by mutations in the genes imd or IKKg, indicating that Diedel functions as an immunosuppressor cytokine targeting the IMD pathway. Homologues of Diedel are found in the genome of several DNA viruses, providing the first example of virokines in insects. Our results reveal that, besides RNA interference and apoptosis, an NF-kB pathway of inducible defense exerts evolutionary pressure on insect viruses. For each experimental condition (non infected and SINV infected), two biologically independent samples composed of 45 males of w1118 or Diedelcfm null mutant flies were used. Infection has been performed by injecting viral stocks prepared in Tris solution. Flies were then incubated for days at 29Â°C.

2016-01-07 | E-GEOD-68174 | biostudies-arrayexpress

RNA sequencing of Aedes mosquitoes infected with Zika virus (ZIKV) or Dengue virus (DENV)

Project description:Zika virus (ZIKV), a pathogen of global health concern, is transmitted to humans by Aedes mosquitoes. However, the molecular interactions between the vector and the virus remain largely unexplored. We demonstrated that ZIKV and dengue virus (DENV) have similar tropism and infection kinetics in two mosquito strains with different degrees of susceptibility to infection. Comparison of Aedes aegypti’s molecular responses to ZIKV and DENV infection indicated that around 40% of the mosquito’s infection-responsive transcriptome is virus-specific. Regulated genes also included key factors of the mosquito’s anti-viral immunity, pointing to the possible involvement of the Toll innate immune pathway. Comparison of ZIKV and DENV infection-responsive transcriptome data to those for yellow fever virus and West Nile virus identified 26 genes likely to play key roles in virus infection of Aedes mosquitoes. Through reverse genetic analyses, we showed that the Toll and the Jak/Stat innate immune pathways mediate increased resistance to ZIKV infection, and the virus use vATPase and inosine-5’-monophosphate dehydrogenase as mosquito’s host factors.

2017-11-07 | GSE96605 | GEO

lncRNA-CR46018 as a positive regulator controls Drosophila Toll immune response by interacting with Dif/Dorsal  

Project description:The Toll signaling pathway is highly conserved from insects to mammals. Drosophila is a model species that is commonly used to study innate immunity. Although many studies have assessed protein-coding genes that regulate the Toll pathway, it is unclear whether long noncoding RNAs (lncRNAs) play regulatory roles in the Toll pathway. Here, we evaluated the expression of the lncRNA CR46018 in Drosophila. Our results showed that this lncRNA was significantly overexpressed after infection of Drosophila with Micrococcus luteus. A CR46018-overexpressing Drosophila strain was then constructed; we expected that CR46018 overexpression would enhance the expression of various antimicrobial peptides downstream of the Toll pathway, regardless of infection with M. luteus. RNA-seq analysis of CR46018-overexpressing Drosophila after infection with M. luteus showed that upregulated genes were mainly enriched in Toll and Imd signaling pathways. Moreover, bioinformatics predictions and RNA-immunoprecipitation experiments showed that CR46018 interacted with the transcription factors Dif and Dorsal to enhance the Toll pathway. During gram-positive bacterial infection, flies overexpressing CR46018 showed favorable survival compared with flies in the control group. Based on these findings, we renamed CR46018 as lncRNA-RDIP. Overall, our current work not only reveals a new immune regulatory factor, lncRNA-RDIP, and explores its potential regulatory model, but also provides a new perspective for the effect of immune disorders on the survival of Drosophila melanogaster.

2021-05-20 | GSE174684 | GEO

The cytokine DIEDEL and a viral homologue suppress deleterious IMD-dependent gene expression in drosophila

2016-01-07 | GSE68174 | GEO

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