Intranet
Acces
Contact
Accès direct
Unités de recherche
Bienvenue
I2CT
Immunologie, Immunopathologie et Chimie Thérapeutique
Publications
2021
Wehbe Layale Salem, Barakat Dana, Acker Adrian, Khoury Rita El, Reichhart Jean-Marc, Matt Nicolas, Chamy Laure El
Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Immune Response Article de journal
Dans: J Immunol, vol. 207, no. 6, p. 1616–1626, 2021, ISSN: 1550-6606.
Résumé | Liens | BibTeX | Étiquettes: Drosophila, IKK complex, IMD, immune response, M3i, matt, NF-κB, PP4 complex
@article{pmid34452932,
title = {Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Immune Response},
author = {Layale Salem Wehbe and Dana Barakat and Adrian Acker and Rita El Khoury and Jean-Marc Reichhart and Nicolas Matt and Laure El Chamy},
doi = {10.4049/jimmunol.1901497},
issn = {1550-6606},
year = {2021},
date = {2021-08-27},
urldate = {2021-08-27},
journal = {J Immunol},
volume = {207},
number = {6},
pages = {1616--1626},
abstract = {The evolutionarily conserved immune deficiency (IMD) signaling pathway shields against bacterial infections. It regulates the expression of antimicrobial peptides encoding genes through the activation of the NF-κB transcription factor Relish. Tight regulation of the signaling cascade ensures a balanced immune response, which is otherwise highly harmful. Several phosphorylation events mediate intracellular progression of the IMD pathway. However, signal termination by dephosphorylation remains largely elusive. Here, we identify the highly conserved protein phosphatase 4 (PP4) complex as a bona fide negative regulator of the IMD pathway. RNA interference-mediated gene silencing of , , and which encode the catalytic and regulatory subunits of the phosphatase complex, respectively, caused a marked upregulation of bacterial-induced antimicrobial peptide gene expression in both S2 cells and adult flies. Deregulated IMD signaling is associated with reduced lifespan of -deficient flies in the absence of any infection. In contrast, flies overexpressing this phosphatase are highly sensitive to bacterial infections. Altogether, our results highlight an evolutionarily conserved function of PP4c in the regulation of NF-κB signaling from to mammals.},
keywords = {Drosophila, IKK complex, IMD, immune response, M3i, matt, NF-κB, PP4 complex},
pubstate = {published},
tppubtype = {article}
}
The evolutionarily conserved immune deficiency (IMD) signaling pathway shields against bacterial infections. It regulates the expression of antimicrobial peptides encoding genes through the activation of the NF-κB transcription factor Relish. Tight regulation of the signaling cascade ensures a balanced immune response, which is otherwise highly harmful. Several phosphorylation events mediate intracellular progression of the IMD pathway. However, signal termination by dephosphorylation remains largely elusive. Here, we identify the highly conserved protein phosphatase 4 (PP4) complex as a bona fide negative regulator of the IMD pathway. RNA interference-mediated gene silencing of , , and which encode the catalytic and regulatory subunits of the phosphatase complex, respectively, caused a marked upregulation of bacterial-induced antimicrobial peptide gene expression in both S2 cells and adult flies. Deregulated IMD signaling is associated with reduced lifespan of -deficient flies in the absence of any infection. In contrast, flies overexpressing this phosphatase are highly sensitive to bacterial infections. Altogether, our results highlight an evolutionarily conserved function of PP4c in the regulation of NF-κB signaling from to mammals.
2018
Issa Najwa, Guillaumot Nina, Lauret Emilie, Matt Nicolas, Scaeffer-Reiss Christine, Dorsselaer Alain Van, Reichhart Jean-Marc, Veillard Florian
The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway. Article de journal
Dans: Molecular Cell, vol. 69, no. 4, p. 539-550, 2018, ISSN: 1097-2765.
Résumé | Liens | BibTeX | Étiquettes: circulating protease, immune sensor, M3i, matt, persephone, Protease, proteolitic activities, reichhart, toll pathway
@article{Issa2018,
title = {The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway.},
author = {Najwa Issa and Nina Guillaumot and Emilie Lauret and Nicolas Matt and Christine Scaeffer-Reiss and Alain Van Dorsselaer and Jean-Marc Reichhart and Florian Veillard},
url = {http://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30058-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276518300583%3Fshowall%3Dtrue},
doi = {10.1016/j.molcel.2018.01.029},
issn = {1097-2765},
year = {2018},
date = {2018-02-15},
journal = {Molecular Cell},
volume = {69},
number = {4},
pages = {539-550},
abstract = {Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.},
keywords = {circulating protease, immune sensor, M3i, matt, persephone, Protease, proteolitic activities, reichhart, toll pathway},
pubstate = {published},
tppubtype = {article}
}
Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.
2017
Koltun Bella, Shackelford Eliza, Bonnay François, Matt Nicolas, Reichhart Jean-Marc, Orian Amir
The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity Article de journal
Dans: The International Journal of Developmental Biology, vol. 61, no. 3-4-5, p. 319–327, 2017, ISSN: 0214-6282.
Liens | BibTeX | Étiquettes: Dgrn, Drosophila, innate immunity, Ligase, M3i, matt, reichhart, SUMO, target, ubiquitin
@article{koltun_sumo-targeted_2017,
title = {The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity},
author = {Bella Koltun and Eliza Shackelford and François Bonnay and Nicolas Matt and Jean-Marc Reichhart and Amir Orian},
url = {http://www.intjdevbiol.com/paper.php?doi=160250ao},
doi = {10.1387/ijdb.160250ao},
issn = {0214-6282},
year = {2017},
date = {2017-01-01},
urldate = {2017-07-12},
journal = {The International Journal of Developmental Biology},
volume = {61},
number = {3-4-5},
pages = {319--327},
keywords = {Dgrn, Drosophila, innate immunity, Ligase, M3i, matt, reichhart, SUMO, target, ubiquitin},
pubstate = {published},
tppubtype = {article}
}
Chamy Laure El, Matt Nicolas, Reichhart Jean-Marc
Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster Article de journal
Dans: Microbiology Spectrum, vol. 5, no. 1, 2017, ISSN: 2165-0497.
Liens | BibTeX | Étiquettes: Drosophila melanogaster, M3i, matt, Myeloid-Like Cell Origins, reichhart
@article{Chamy2017,
title = {Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster},
author = {Laure El Chamy and Nicolas Matt and Jean-Marc Reichhart},
url = {http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0038-2016},
doi = {10.1128/microbiolspec.MCHD-0038-2016},
issn = {2165-0497},
year = {2017},
date = {2017-01-01},
urldate = {2017-07-12},
journal = {Microbiology Spectrum},
volume = {5},
number = {1},
keywords = {Drosophila melanogaster, M3i, matt, Myeloid-Like Cell Origins, reichhart},
pubstate = {published},
tppubtype = {article}
}
2015
Chamy Laure El, Matt Nicolas, Ntwasa Monde, Reichhart Jean-Marc
The multilayered innate immune defense of the gut Article de journal
Dans: Biomed J, vol. 38, no. 4, p. 276–284, 2015, ISSN: 2320-2890.
Résumé | Liens | BibTeX | Étiquettes: fly, gut, innate immunity, M3i, matt, reichhart
@article{el_chamy_multilayered_2015,
title = {The multilayered innate immune defense of the gut},
author = {Laure El Chamy and Nicolas Matt and Monde Ntwasa and Jean-Marc Reichhart},
url = {http://www.biomedj.org/text.asp?2015/38/4/276/158621},
doi = {10.4103/2319-4170.158621},
issn = {2320-2890},
year = {2015},
date = {2015-08-01},
journal = {Biomed J},
volume = {38},
number = {4},
pages = {276--284},
abstract = {In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.},
keywords = {fly, gut, innate immunity, M3i, matt, reichhart},
pubstate = {published},
tppubtype = {article}
}
In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.
2014
Bonnay François, Nguyen Xuan-Hung, Cohen-Berros Eva, Troxler Laurent, Batsche Eric, Camonis Jacques, Takeuchi Osamu, Reichhart Jean-Marc, Matt Nicolas
Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling Article de journal
Dans: EMBO J., vol. 33, no. 20, p. 2349–2362, 2014, ISSN: 1460-2075.
Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques
@article{bonnay_akirin_2014,
title = {Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling},
author = {François Bonnay and Xuan-Hung Nguyen and Eva Cohen-Berros and Laurent Troxler and Eric Batsche and Jacques Camonis and Osamu Takeuchi and Jean-Marc Reichhart and Nicolas Matt},
doi = {10.15252/embj.201488456},
issn = {1460-2075},
year = {2014},
date = {2014-10-01},
journal = {EMBO J.},
volume = {33},
number = {20},
pages = {2349--2362},
abstract = {The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.},
keywords = {Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques},
pubstate = {published},
tppubtype = {article}
}
The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.
2013
Bonnay François, Cohen-Berros Eva, Hoffmann Martine, Kim Sabrina Y, Boulianne Gabrielle L, Hoffmann Jules A, Matt Nicolas, Reichhart Jean-Marc
Big bang gene modulates gut immune tolerance in Drosophila Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 110, no. 8, p. 2957–2962, 2013, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Animals, hoffmann, Immune Tolerance, Longevity, M3i, matt, Membrane Proteins, reichhart
@article{bonnay_big_2013,
title = {Big bang gene modulates gut immune tolerance in Drosophila},
author = {François Bonnay and Eva Cohen-Berros and Martine Hoffmann and Sabrina Y Kim and Gabrielle L Boulianne and Jules A Hoffmann and Nicolas Matt and Jean-Marc Reichhart},
doi = {10.1073/pnas.1221910110},
issn = {1091-6490},
year = {2013},
date = {2013-02-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {110},
number = {8},
pages = {2957--2962},
abstract = {Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.},
keywords = {Animals, hoffmann, Immune Tolerance, Longevity, M3i, matt, Membrane Proteins, reichhart},
pubstate = {published},
tppubtype = {article}
}
Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.
2011
Aoun Richard Bou, Hetru Charles, Troxler Laurent, Doucet Daniel, Ferrandon Dominique, Matt Nicolas
Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster Article de journal
Dans: J Innate Immun, vol. 3, no. 1, p. 52–64, 2011, ISSN: 1662-8128.
Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, DNA, Evolution, ferrandon, Gene Expression Regulation, Hemocytes, Immunity, In Situ Hybridization, Innate, M3i, matt, Molecular, Mutation, Phylogeny, Sequence Analysis
@article{bou_aoun_analysis_2011,
title = {Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster},
author = {Richard Bou Aoun and Charles Hetru and Laurent Troxler and Daniel Doucet and Dominique Ferrandon and Nicolas Matt},
doi = {10.1159/000321554},
issn = {1662-8128},
year = {2011},
date = {2011-01-01},
journal = {J Innate Immun},
volume = {3},
number = {1},
pages = {52--64},
abstract = {Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.},
keywords = {Animals, bioinformatic, DNA, Evolution, ferrandon, Gene Expression Regulation, Hemocytes, Immunity, In Situ Hybridization, Innate, M3i, matt, Molecular, Mutation, Phylogeny, Sequence Analysis},
pubstate = {published},
tppubtype = {article}
}
Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.
2008
Deddouche Safia, Matt Nicolas, Budd Aidan, Mueller Stefanie, Kemp Cordula, Galiana-Arnoux Delphine, Dostert Catherine, Antoniewski Christophe, Hoffmann Jules A, Imler Jean-Luc
The DExD/Ħ-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila Article de journal
Dans: Nature Immunology, vol. 9, no. 12, p. 1425–1432, 2008, ISSN: 1529-2916.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Electrophoresis, Fat Body, Gene Expression Regulation, Genetic, Genetically Modified, hoffmann, Humans, imler, M3i, matt, Phylogeny, Polyacrylamide Gel, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA Helicases, Sequence Homology, Transcription, Virus Diseases
@article{deddouche_dexd/h-box_2008,
title = {The DExD/Ħ-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila},
author = {Safia Deddouche and Nicolas Matt and Aidan Budd and Stefanie Mueller and Cordula Kemp and Delphine Galiana-Arnoux and Catherine Dostert and Christophe Antoniewski and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni.1664},
issn = {1529-2916},
year = {2008},
date = {2008-12-01},
journal = {Nature Immunology},
volume = {9},
number = {12},
pages = {1425--1432},
abstract = {Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.},
keywords = {Amino Acid, Animals, Electrophoresis, Fat Body, Gene Expression Regulation, Genetic, Genetically Modified, hoffmann, Humans, imler, M3i, matt, Phylogeny, Polyacrylamide Gel, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA Helicases, Sequence Homology, Transcription, Virus Diseases},
pubstate = {published},
tppubtype = {article}
}
Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.