Publications
2022
de Faria Isaque J. S., Aguiar Eric R. G. R., Olmo Roenick P., da Silva Juliana Alves, Daeffler Laurent, Carthew Richard W., Imler Jean-Luc, Marques Joao T.
Invading viral DNA triggers dsRNA synthesis by RNA polymerase II to activate antiviral RNA interference in Drosophila Journal Article
In: Cell Reports, vol. 39, pp. 110976, 2022.
Abstract | Links | BibTeX | Tags: antiviral, Drosophila, dsRNA, imler, M3i, Marques, protocol, RNA Interference
@article{dedaMarques2022,
title = {Invading viral DNA triggers dsRNA synthesis by RNA polymerase II to activate antiviral RNA interference in Drosophila},
author = {Isaque J.S. de Faria and Eric R.G.R. Aguiar and Roenick P. Olmo and Juliana Alves da Silva and Laurent Daeffler and Richard W. Carthew and Jean-Luc Imler and Joao T. Marques},
doi = {10.1016/j.celrep.2022.110976},
year = {2022},
date = {2022-06-21},
urldate = {2022-06-21},
journal = {Cell Reports},
volume = {39},
pages = {110976},
abstract = {dsRNA sensing triggers antiviral responses against RNA and DNA viruses in diverse eukaryotes. In Drosophila, Invertebrate iridescent virus 6 (IIV-6), a large DNA virus, triggers production of small interfering RNAs (siRNAs) by the dsRNA sensor Dicer-2. Here, we show that host RNA polymerase II (RNAPII) bidirec- tionally transcribes specific AT-rich regions of the IIV-6 DNA genome to generate dsRNA. Both replicative and naked IIV-6 genomes trigger production of dsRNA in Drosophila cells, implying direct sensing of invading DNA. Loquacious-PD, a Dicer-2 co-factor essential for the biogenesis of endogenous siRNAs, is dispensable for processing of IIV-6-derived dsRNAs, which suggests that they are distinct. Consistent with this finding, inhibition of the RNAPII co-factor P-TEFb affects the synthesis of endogenous, but not virus-derived, dsRNA. Altogether, our results suggest that a non-canonical RNAPII complex recognizes invading viral DNA to synthesize virus-derived dsRNA, which activates the antiviral siRNA pathway in Drosophila.},
keywords = {antiviral, Drosophila, dsRNA, imler, M3i, Marques, protocol, RNA Interference},
pubstate = {published},
tppubtype = {article}
}
2020
Aguiar ERGR, de Almeida JPP, Queiroz LR, Oliveira LS, Olmo RP, de Faria IJDS, Imler JL, Gruber A, Matthews BJ, Marques JT
In: RNA, vol. 26, no. 5, pp. 581-594, 2020.
Abstract | Links | BibTeX | Tags: A. aegypti, Aedes aegypti, endogenous viral elements, EVE, flamenco locus, imler, M3i, Marques, piRNA, piRNAs, RNA Interference
@article{Aguiar_2020,
title = {A single unidirectional piRNA cluster similar to the flamenco locus is the major source of EVE-derived transcription and small RNAs in Aedes aegypti mosquitoes },
author = {ERGR Aguiar and JPP de Almeida and LR Queiroz and LS Oliveira and RP Olmo and IJDS de Faria and JL Imler and A Gruber and BJ Matthews and JT Marques},
url = {https://rnajournal.cshlp.org/content/26/5/581.long},
doi = {10.1261/rna.073965.119},
year = {2020},
date = {2020-01-29},
journal = {RNA},
volume = {26},
number = {5},
pages = {581-594},
abstract = {Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster. },
keywords = {A. aegypti, Aedes aegypti, endogenous viral elements, EVE, flamenco locus, imler, M3i, Marques, piRNA, piRNAs, RNA Interference},
pubstate = {published},
tppubtype = {article}
}
2019
Olmo RP, Martins NE, Aguiar ERGR, Marques JT, Imler JL
The insect reservoir of biodiversity for viruses and for antiviral mechanisms Journal Article
In: An Acad Bras Cienc , vol. 91, no. Suppl 3, pp. e20190122, 2019.
Abstract | Links | BibTeX | Tags: antiviral immunity, imler, insects, M3i, Marques, metagenomics, restriction factors, RNA Interference, virome
@article{Olmo_2019,
title = {The insect reservoir of biodiversity for viruses and for antiviral mechanisms},
author = {RP Olmo and NE Martins and ERGR Aguiar and JT Marques and JL Imler},
url = {https://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652019000600604&lng=en&nrm=iso&tlng=en},
doi = {10.1590/0001-3765201920190122},
year = {2019},
date = {2019-06-03},
journal = { An Acad Bras Cienc },
volume = {91},
number = {Suppl 3},
pages = {e20190122},
abstract = {Insects are the most diverse group of animals. They can be infected by an extraordinary diversity of viruses. Among them, arthropod-borne viruses (arboviruses) can be transmitted to humans. High-throughput sequencing of small RNAs from insects provides insight into their virome, which may help understand the dynamics of vector borne infectious diseases. Furthermore, investigating the mechanisms that restrict viral infections in insects points to genetic innovations that may inspire novel antiviral strategies. },
keywords = {antiviral immunity, imler, insects, M3i, Marques, metagenomics, restriction factors, RNA Interference, virome},
pubstate = {published},
tppubtype = {article}
}
2018
Ferreira Flávia Viana, Aguiar Eric Roberto Guimarães Rocha, Olmo Roenick Proveti, de Oliveira Karla Pollyanna Vieira, Silva Emanuele Guimarães, Sant'Anna Maurício Roberto Viana, de Gontijo Nelder Figueiredo, Kroon Erna Geessien, Imler Jean-Luc, Marques João Trindade
The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis Journal Article
In: PLoS Negl Trop Dis, vol. 12, no. 6, pp. e0006569, 2018, ISSN: 1935-2735.
Abstract | Links | BibTeX | Tags: Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral
@article{ferreira_small_2018,
title = {The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis},
author = {Flávia Viana Ferreira and Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Karla Pollyanna Vieira de Oliveira and Emanuele Guimarães Silva and Maurício Roberto Viana Sant'Anna and Nelder Figueiredo de Gontijo and Erna Geessien Kroon and Jean-Luc Imler and João Trindade Marques},
doi = {10.1371/journal.pntd.0006569},
issn = {1935-2735},
year = {2018},
date = {2018-01-01},
journal = {PLoS Negl Trop Dis},
volume = {12},
number = {6},
pages = {e0006569},
abstract = {Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.},
keywords = {Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral},
pubstate = {published},
tppubtype = {article}
}
2011
Eleftherianos Ioannis, Won Sungyong, Chtarbanova Stanislava, Squiban Barbara, Ocorr Karen, Bodmer Rolf, Beutler Bruce, Hoffmann Jules A, Imler Jean-Luc
ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 29, pp. 12024–12029, 2011, ISSN: 1091-6490.
Abstract | Links | BibTeX | Tags: Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia
@article{eleftherianos_atp-sensitive_2011,
title = {ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections},
author = {Ioannis Eleftherianos and Sungyong Won and Stanislava Chtarbanova and Barbara Squiban and Karen Ocorr and Rolf Bodmer and Bruce Beutler and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1073/pnas.1108926108},
issn = {1091-6490},
year = {2011},
date = {2011-07-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {108},
number = {29},
pages = {12024--12029},
abstract = {The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.},
keywords = {Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia},
pubstate = {published},
tppubtype = {article}
}
Al-Jamal Khuloud T, Gherardini Lisa, Bardi Giuseppe, Nunes Antonio, Guo Chang, Bussy Cyrill, Herrero Antonia M, Bianco Alberto, Prato Maurizio, Kostarelos Kostas, Pizzorusso Tommaso
Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 27, pp. 10952–10957, 2011, ISSN: 1091-6490.
Abstract | Links | BibTeX | Tags: Animals, Apoptosis, Base Sequence, Brain Ischemia, carbon, Caspase 3, Caspase Inhibitors, Cell Line, Cells, Cultured, Electron, Endothelin-1, Female, Genetic Therapy, I2CT, Inbred C57BL, Mice, Microscopy, Nanomedicine, Nanotubes, Neurons, Psychomotor Performance, Rats, RNA, RNA Interference, Small Interfering, Sprague-Dawley, Team-Bianco, Transmission
@article{al-jamal_functional_2011,
title = {Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing},
author = {Khuloud T Al-Jamal and Lisa Gherardini and Giuseppe Bardi and Antonio Nunes and Chang Guo and Cyrill Bussy and Antonia M Herrero and Alberto Bianco and Maurizio Prato and Kostas Kostarelos and Tommaso Pizzorusso},
doi = {10.1073/pnas.1100930108},
issn = {1091-6490},
year = {2011},
date = {2011-07-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {108},
number = {27},
pages = {10952--10957},
abstract = {Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.},
keywords = {Animals, Apoptosis, Base Sequence, Brain Ischemia, carbon, Caspase 3, Caspase Inhibitors, Cell Line, Cells, Cultured, Electron, Endothelin-1, Female, Genetic Therapy, I2CT, Inbred C57BL, Mice, Microscopy, Nanomedicine, Nanotubes, Neurons, Psychomotor Performance, Rats, RNA, RNA Interference, Small Interfering, Sprague-Dawley, Team-Bianco, Transmission},
pubstate = {published},
tppubtype = {article}
}
2009
Kemp Cordula, Imler Jean-Luc
Antiviral immunity in drosophila Journal Article
In: Current Opinion in Immunology, vol. 21, no. 1, pp. 3–9, 2009, ISSN: 1879-0372.
Abstract | Links | BibTeX | Tags: Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence
@article{kemp_antiviral_2009,
title = {Antiviral immunity in drosophila},
author = {Cordula Kemp and Jean-Luc Imler},
doi = {10.1016/j.coi.2009.01.007},
issn = {1879-0372},
year = {2009},
date = {2009-02-01},
journal = {Current Opinion in Immunology},
volume = {21},
number = {1},
pages = {3--9},
abstract = {Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals.},
keywords = {Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence},
pubstate = {published},
tppubtype = {article}
}
Berry Bassam, Deddouche Safia, Kirschner Doris, Imler Jean-Luc, Antoniewski Christophe
Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila Journal Article
In: PloS One, vol. 4, no. 6, pp. e5866, 2009, ISSN: 1932-6203.
Abstract | Links | BibTeX | Tags: Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes
@article{berry_viral_2009,
title = {Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila},
author = {Bassam Berry and Safia Deddouche and Doris Kirschner and Jean-Luc Imler and Christophe Antoniewski},
doi = {10.1371/journal.pone.0005866},
issn = {1932-6203},
year = {2009},
date = {2009-01-01},
journal = {PloS One},
volume = {4},
number = {6},
pages = {e5866},
abstract = {BACKGROUND: In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs). CONCLUSIONS/SIGNIFICANCE: Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections.},
keywords = {Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes},
pubstate = {published},
tppubtype = {article}
}
Cronin Shane J F, Nehme Nadine T, Limmer Stefanie, Liegeois Samuel, Pospisilik Andrew J, Schramek Daniel, Leibbrandt Andreas, de Simoes Ricardo Matos, Gruber Susanne, Puc Urszula, Ebersberger Ingo, Zoranovic Tamara, Neely Gregory G, von Haeseler Arndt, Ferrandon Dominique, Penninger Josef M
Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection Journal Article
In: Science, vol. 325, no. 5938, pp. 340–343, 2009, ISSN: 1095-9203.
Abstract | Links | BibTeX | Tags: *Genome, *RNA Interference, Animal, Animals, Cell Proliferation, Drosophila melanogaster/*genetics/immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, ferrandon, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/*genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, M3i, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/*immunology/microbiology, Serratia marcescens, Serratia marcescens/*immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology
@article{cronin_genome-wide_2009b,
title = {Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection},
author = {Shane J F Cronin and Nadine T Nehme and Stefanie Limmer and Samuel Liegeois and Andrew J Pospisilik and Daniel Schramek and Andreas Leibbrandt and Ricardo Matos de Simoes and Susanne Gruber and Urszula Puc and Ingo Ebersberger and Tamara Zoranovic and Gregory G Neely and Arndt von Haeseler and Dominique Ferrandon and Josef M Penninger},
doi = {10.1126/science.1173164},
issn = {1095-9203},
year = {2009},
date = {2009-01-01},
journal = {Science},
volume = {325},
number = {5938},
pages = {340--343},
abstract = {Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.},
keywords = {*Genome, *RNA Interference, Animal, Animals, Cell Proliferation, Drosophila melanogaster/*genetics/immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, ferrandon, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/*genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, M3i, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/*immunology/microbiology, Serratia marcescens, Serratia marcescens/*immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology},
pubstate = {published},
tppubtype = {article}
}
2008
Huszar Tünde, Imler Jean-Luc
Drosophila viruses and the study of antiviral host-defense Journal Article
In: Advances in Virus Research, vol. 72, pp. 227–265, 2008, ISSN: 0065-3527.
Abstract | Links | BibTeX | Tags: Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses
@article{huszar_drosophila_2008,
title = {Drosophila viruses and the study of antiviral host-defense},
author = {Tünde Huszar and Jean-Luc Imler},
doi = {10.1016/S0065-3527(08)00406-5},
issn = {0065-3527},
year = {2008},
date = {2008-01-01},
journal = {Advances in Virus Research},
volume = {72},
pages = {227--265},
abstract = {The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors.},
keywords = {Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses},
pubstate = {published},
tppubtype = {article}
}
2007
Müller Stefanie, Imler Jean-Luc
Dicing with viruses: microRNAs as antiviral factors Journal Article
In: Immunity, vol. 27, no. 1, pp. 1–3, 2007, ISSN: 1074-7613.
Abstract | Links | BibTeX | Tags: Animals, DEAD-box RNA Helicases, Endoribonucleases, imler, M3i, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections
@article{muller_dicing_2007,
title = {Dicing with viruses: microRNAs as antiviral factors},
author = {Stefanie Müller and Jean-Luc Imler},
doi = {10.1016/j.immuni.2007.07.003},
issn = {1074-7613},
year = {2007},
date = {2007-07-01},
journal = {Immunity},
volume = {27},
number = {1},
pages = {1--3},
abstract = {In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV.},
keywords = {Animals, DEAD-box RNA Helicases, Endoribonucleases, imler, M3i, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections},
pubstate = {published},
tppubtype = {article}
}
2006
Galiana-Arnoux Delphine, Dostert Catherine, Schneemann Anette, Hoffmann Jules A, Imler Jean-Luc
Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila Journal Article
In: Nature Immunology, vol. 7, no. 6, pp. 590–597, 2006, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Genetically Modified, hoffmann, imler, M3i, Mutation, Nodaviridae, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Viruses, Viral, Viral Proteins, Virus Replication
@article{galiana-arnoux_essential_2006,
title = {Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila},
author = {Delphine Galiana-Arnoux and Catherine Dostert and Anette Schneemann and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni1335},
issn = {1529-2908},
year = {2006},
date = {2006-06-01},
journal = {Nature Immunology},
volume = {7},
number = {6},
pages = {590--597},
abstract = {The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections.},
keywords = {Animals, Genetically Modified, hoffmann, imler, M3i, Mutation, Nodaviridae, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Viruses, Viral, Viral Proteins, Virus Replication},
pubstate = {published},
tppubtype = {article}
}
Bischoff Vincent, Vignal Cécile, Duvic Bernard, Boneca Ivo G, Hoffmann Jules A, Royet Julien
Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2 Journal Article
In: PLoS Pathog., vol. 2, no. 2, pp. e14, 2006, ISSN: 1553-7374.
Abstract | Links | BibTeX | Tags: Animals, Antimicrobial Cationic Peptides, bacteria, Carrier Proteins, Down-Regulation, hoffmann, Larva, M3i, RNA Interference, Signal Transduction
@article{bischoff_downregulation_2006,
title = {Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2},
author = {Vincent Bischoff and Cécile Vignal and Bernard Duvic and Ivo G Boneca and Jules A Hoffmann and Julien Royet},
doi = {10.1371/journal.ppat.0020014},
issn = {1553-7374},
year = {2006},
date = {2006-02-01},
journal = {PLoS Pathog.},
volume = {2},
number = {2},
pages = {e14},
abstract = {Peptidoglycan-recognition proteins (PGRPs) are evolutionarily conserved molecules that are structurally related to bacterial amidases. Several Drosophila PGRPs have lost this enzymatic activity and serve as microbe sensors through peptidoglycan recognition. Other PGRP family members, such as Drosophila PGRP-SC1 or mammalian PGRP-L, have conserved the amidase function and are able to cleave peptidoglycan in vitro. However, the contribution of these amidase PGRPs to host defense in vivo has remained elusive so far. Using an RNA-interference approach, we addressed the function of two PGRPs with amidase activity in the Drosophila immune response. We observed that PGRP-SC1/2-depleted flies present a specific over-activation of the IMD (immune deficiency) signaling pathway after bacterial challenge. Our data suggest that these proteins act in the larval gut to prevent activation of this pathway following bacterial ingestion. We further show that a strict control of IMD-pathway activation is essential to prevent bacteria-induced developmental defects and larval death.},
keywords = {Animals, Antimicrobial Cationic Peptides, bacteria, Carrier Proteins, Down-Regulation, hoffmann, Larva, M3i, RNA Interference, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
2005
Kocks Christine, Cho Ju Hyun, Nehme Nadine, Ulvila Johanna, Pearson Alan M, Meister Marie, Strom Charles, Conto Stephanie L, Hetru Charles, Stuart Lynda M, Stehle Thilo, Hoffmann Jules A, Reichhart Jean-Marc, Ferrandon Dominique, Rämet Mika, Ezekowitz Alan R B
Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila Journal Article
In: Cell, vol. 123, no. 2, pp. 335–346, 2005, ISSN: 0092-8674.
Abstract | Links | BibTeX | Tags: Amino Acid, Amino Acid Motifs, Animals, Bacterial Infections, Cell Surface, Embryo, Escherichia coli, ferrandon, Flow Cytometry, Frameshift Mutation, Genes, Histidine, hoffmann, In Situ Hybridization, Insect, Insect Proteins, M3i, Macrophages, Membrane Proteins, messenger, Nonmammalian, Open Reading Frames, Phagocytosis, Receptors, reichhart, RNA, RNA Interference, Sequence Homology, Serratia marcescens
@article{kocks_eater_2005,
title = {Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila},
author = {Christine Kocks and Ju Hyun Cho and Nadine Nehme and Johanna Ulvila and Alan M Pearson and Marie Meister and Charles Strom and Stephanie L Conto and Charles Hetru and Lynda M Stuart and Thilo Stehle and Jules A Hoffmann and Jean-Marc Reichhart and Dominique Ferrandon and Mika Rämet and Alan R B Ezekowitz},
doi = {10.1016/j.cell.2005.08.034},
issn = {0092-8674},
year = {2005},
date = {2005-10-01},
journal = {Cell},
volume = {123},
number = {2},
pages = {335--346},
abstract = {Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.},
keywords = {Amino Acid, Amino Acid Motifs, Animals, Bacterial Infections, Cell Surface, Embryo, Escherichia coli, ferrandon, Flow Cytometry, Frameshift Mutation, Genes, Histidine, hoffmann, In Situ Hybridization, Insect, Insect Proteins, M3i, Macrophages, Membrane Proteins, messenger, Nonmammalian, Open Reading Frames, Phagocytosis, Receptors, reichhart, RNA, RNA Interference, Sequence Homology, Serratia marcescens},
pubstate = {published},
tppubtype = {article}
}
2003
Goto Akira, Blandin Stéphanie A, Royet Julien, Reichhart Jean-Marc, Levashina Elena A
Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies Journal Article
In: Nucleic Acids Res., vol. 31, no. 22, pp. 6619–6623, 2003, ISSN: 1362-4962.
Abstract | BibTeX | Tags: Animals, blandin, Cell Surface, Double-Stranded, Epistasis, Female, Genetic, Green Fluorescent Proteins, Homeodomain Proteins, Luminescent Proteins, M3i, Phenotype, Receptors, reichhart, RNA, RNA Interference, Serpins, Signal Transduction, Time Factors, Toll-Like Receptors, Transcription Factors
@article{goto_silencing_2003,
title = {Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies},
author = {Akira Goto and Stéphanie A Blandin and Julien Royet and Jean-Marc Reichhart and Elena A Levashina},
issn = {1362-4962},
year = {2003},
date = {2003-11-01},
journal = {Nucleic Acids Res.},
volume = {31},
number = {22},
pages = {6619--6623},
abstract = {Double-stranded RNA (dsRNA) gene interference is an efficient method to silence gene expression in a sequence-specific manner. Here we show that the direct injection of dsRNA can be used in adult Drosophila flies to disrupt function of endogenous genes in vivo. As a proof of principle, we have used this method to silence components of a major signaling cascade, the Toll pathway, which controls fruit fly resistance to fungal and Gram-positive bacterial infections. We demonstrate that the knockout is efficient only if dsRNA is injected in 4- or more day-old flies and that it lasts for at least 1 week. Furthermore, we report dsRNA-based epistatic gene analysis via injection of a mixture of two dsRNAs and propose that injection of dsRNA represents a powerful method for rapid functional analysis of genes in Drosophila melanogaster adults, particularly of those whose mutations are lethal during development.},
keywords = {Animals, blandin, Cell Surface, Double-Stranded, Epistasis, Female, Genetic, Green Fluorescent Proteins, Homeodomain Proteins, Luminescent Proteins, M3i, Phenotype, Receptors, reichhart, RNA, RNA Interference, Serpins, Signal Transduction, Time Factors, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}