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

ABSTRACT: 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE68174 | GEO | 2016/01/07

SECONDARY ACCESSION(S): PRJNA281952

REPOSITORIES: GEO

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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

Expression data from D. melanogaster guts with suppression of Imd in progenitors or enterocytes

Project description:We used RNA-seq to examine transcriptional proflies of midguts with suppression of Imd in progenitors (e_* samples) or enterocytes (M_* samples) . We found significant differences between the contributions of enterocyte IMD and progenitor IMD to intestinal homeostasis.

2019-08-01 | GSE135154 | GEO

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

Effect of IMD-0354 on gene expression in melanoma A375 cells

Project description:The purpose of this RNAseq is to analyse the effect of compound IMD-0354 on gene expression in melanoma A375 cells. RNAseq analysis identified unfolded protein response, cell cycle and DNA damage pathways to be effected by IMD-0354.

2021-02-02 | GSE165899 | GEO

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

2013-01-31 | GSE42726 | GEO

Expression data from D. melanogaster intestinal stem cell with suppression of Imd in progenitors

Project description:We used RNA-seq to examine transcriptional profiles of midgut progenitor cells with suppression of Imd in progenitors. We found significant differences between the contributions of progenitor IMD to intestinal homeostasis.

2021-03-29 | GSE171001 | GEO

Targeted NGS on artificial microRNAs expressed by a pool of heterogeneous Sindbis viruses

Project description:Purpose: Next-generation sequencing (NGS) on targeted locus in Sindbis genome to determine frequency changes of artificial microRNAs expressed by viruses after passaging in cancer and normal cells Methods: RNA was harvested in Trizol 488 (Thermo Fisher). RNA was extracted using the manufacturer’s protocol and quantified by nanodrop. Sequencing was done by SeqMatic on a MiSeq v3 platform generating 75bp reads. Adapters were trimmed using Trimmomatic and adapter-free reads represent artificial microRNAs encoded by Sindbis virus in a sample. Results: We have identified changes in artificial microRNA frequency after passaging virus pool in cancer and normal cells and have identified microRNAs increasing viral fitness in cancer cells. Conclusions: Our study represents artificial microRNAs which target pathways that can aid oncolytic viral replication in cancer cells.

2022-03-02 | GSE197271 | GEO

Single cell expression data from D. melanogaster guts with suppression of Imd in progenitors

Project description:We used Single-cell RNA-seq to examine transcriptional proflies of midguts with suppression of Imd in progenitors.

2019-12-13 | GSE141896 | GEO

Expression data from D.melanogaster larvae with a constitutively active Imd in the fat body

Project description:Activation of innate immune responses in the Drosophila larval fat body affects the physiological host responses. In order to characterize the effect of the activated immune responses in the fat body on the Drosophila, we used whole-genome microarray analysis and found that activation of the immune deficieny pathway (Imd) in the fat body alters the transcriptional profiles of Drosophila larvae. As we expected many of genes involved in regulation of antimicrobial peptides were upregulated in the larvae with elevated Imd activity in the fat body. Notably, we found activatioan of Imd in the fat body negatively affects expression of genes involved in glycolysis, energy production and insulin signaling pathway. Overall, our analysis showed that activation of innate immune signaling in the larval fat body significantly affects cellular pathways that regulate metabolism.

2018-01-24 | GSE109470 | GEO

Relish-mediated lncRNA-CR33942 facilitates Drosophila Imd immune responses and promotes antimicrobial peptide expression via interacting with Relish

Project description:Long noncoding RNAs (lncRNAs), as a class of emerging regulators, play crucial role in regulating the strength and duration of innate immunity. However, little is known about how these Drosophila Imd immunity-related lncRNAs are regulated. Herein, we firstly revealed that overexpression of lncRNA-CR33942 could strengthen the expression of Imd pathway antimicrobial peptides Diptericin (Dpt) and Attacin-A (AttA) after infection, and vice versa. Secondly, RNA-seq analysis of post-infected lncRNA-CR33942-overexpressing flies further confirmed that lncRNA-CR33942 positively regulates the Drosophila Imd pathway. Mechanistically, we indicated that lncRNA-CR33942 interacts with NF-κB transcription factor Relish to promote its binding to Dpt and AttA promoters, thereby facilitating Dpt and AttA expression. Interestingly, we found that Relish can also directly promote lncRNA-CR33942 transcription by binding to its promoter. Finally, rescue experiments and dynamic expression profiling post-infection demonstrated the vital role of the Relish/lncRNA-CR33942/AMPs regulatory axis in enhancing inadequate Imd immune responses and maintaining immune homeostasis. Taken together, our study not only elucidates a novel mechanism about lncRNA in Drosophila Imd immune regulation, but also has important guiding significance for elucidating the complex regulatory mechanism of animal innate immune response.

2022-03-22 | GSE198991 | GEO

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