H Cai, L Li, KM Slavik, J Huang, T Yin, X Ai, L Hédelin, G Haas, Z Xiang, Y Yang, X Li, Y Chen, Z Wei, H Deng, D Chen, R Jiao, N Martins, C Meignin, PJ Kranzusch, JL Imler
The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila Article de journal
Dans: Immunity, vol. 56, iss. 9, p. 1991-2005, 2023.
Résumé | Liens | BibTeX | Étiquettes: c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, Drosophila, Evolution, Hua, imler, M3i, meignin, pattern recognition receptor, STING, virus
@article{nokey,
title = {The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila},
author = {Cai H and Li L and Slavik KM and Huang J and Yin T and Ai X and Hédelin L and Haas G and Xiang Z and Yang Y and Li X and Chen Y and Wei Z and Deng H and Chen D and Jiao R and Martins N and Meignin C and Kranzusch PJ and Imler JL},
editor = {Elsevier Inc. },
url = {https://pubmed.ncbi.nlm.nih.gov/37659413/},
doi = {10.1016/j.immuni.2023.08.006 },
year = {2023},
date = {2023-09-12},
urldate = {2023-09-12},
journal = {Immunity},
volume = {56},
issue = {9},
pages = {1991-2005},
abstract = {In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity. },
keywords = {c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, Drosophila, Evolution, Hua, imler, M3i, meignin, pattern recognition receptor, STING, virus},
pubstate = {published},
tppubtype = {article}
}
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 Article de journal
Dans: Cell Reports, vol. 39, p. 110976, 2022.
Résumé | Liens | BibTeX | Étiquettes: 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}
}
Cai H, Meignin C, Imler JL
cGAS-like receptor-mediated immunity: the insect perspective Article de journal
Dans: Current Opinion in Immunology, vol. 74, p. 183-189, 2022.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i, meignin
@article{Imler2022,
title = {cGAS-like receptor-mediated immunity: the insect perspective},
author = {H Cai and C Meignin and JL Imler},
doi = {10.1016/j.coi.2022.01.005},
year = {2022},
date = {2022-02-08},
urldate = {2022-02-08},
journal = {Current Opinion in Immunology},
volume = {74},
pages = {183-189},
abstract = {The cGAS-STING pathway plays a central role in the detection of DNA in the cytosol of mammalian cells and activation of immunity. Although the early evolutionary origin of this pathway in animals has been noted, its ancestral functions have remained elusive so far. We review here new findings in invertebrates establishing a role in sensing and signaling infection, triggering potent transcriptional responses, in addition to autophagy. Results from flies and moths/butterflies points to the importance of STING signaling in antiviral immunity in insects. The recent characterization of cGAS-like receptors in Drosophila reveals the plasticity of this family of pattern-recognition receptors, able to accommodate ligands different from DNA and to produce cyclic dinucleotides beyond 2′3′-cGAMP.},
keywords = {imler, M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
Pennemann Friederike L, Mussabekova Assel, Urban Christian, Stukalov Alexey, Andersen Line Lykke, Grass Vincent, Lavacca Teresa Maria, Holze Cathleen, Oubraham Lila, Benamrouche Yasmine, Girardi Enrico, Boulos Rasha E, Hartmann Rune, Superti-Furga Giulio, Habjan Matthias, Imler Jean-Luc, Meignin Carine, Pichlmair Andreas
Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators Article de journal
Dans: Nat Commun, vol. 12, no. 1, p. 7009, 2021, ISSN: 2041-1723.
Résumé | Liens | BibTeX | Étiquettes: antiviral innate immunity, imler, M3i, meignin
@article{pmid34853303,
title = {Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators},
author = {Friederike L Pennemann and Assel Mussabekova and Christian Urban and Alexey Stukalov and Line Lykke Andersen and Vincent Grass and Teresa Maria Lavacca and Cathleen Holze and Lila Oubraham and Yasmine Benamrouche and Enrico Girardi and Rasha E Boulos and Rune Hartmann and Giulio Superti-Furga and Matthias Habjan and Jean-Luc Imler and Carine Meignin and Andreas Pichlmair},
doi = {10.1038/s41467-021-27192-w},
issn = {2041-1723},
year = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {Nat Commun},
volume = {12},
number = {1},
pages = {7009},
abstract = {The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses.},
keywords = {antiviral innate immunity, imler, M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
Holleufer Andreas, Winther Kasper Grønbjerg, Gad Hans Henrik, Ai Xianlong, Chen Yuqiang, Li Lihua, Wei Ziming, Deng Huimin, Liu Jiyong, Frederiksen Ninna Ahlmann, Simonsen Bine, Andersen Line Lykke, Kleigrewe Karin, Dalskov Louise, Pichlmair Andreas, Cai Hua, Imler Jean-Luc, Hartmann Rune
Two cGAS-like receptors induce antiviral immunity in Drosophila Article de journal
Dans: Nature, vol. 597, p. 114-118, 2021.
Résumé | Liens | BibTeX | Étiquettes: antiviral immunity, cGAS-like receptors, Drosophila, imler, M3i
@article{Hartmann2021,
title = {Two cGAS-like receptors induce antiviral immunity in Drosophila},
author = {Andreas Holleufer AND Kasper Grønbjerg Winther AND Hans Henrik Gad AND Xianlong Ai AND Yuqiang Chen AND Lihua Li AND Ziming Wei AND Huimin Deng AND Jiyong Liu AND Ninna Ahlmann Frederiksen AND Bine Simonsen AND Line Lykke Andersen AND Karin Kleigrewe AND Louise Dalskov AND Andreas Pichlmair AND Hua Cai AND Jean-Luc Imler AND Rune Hartmann},
editor = {Nature Publishing Group},
doi = {https://doi.org/10.1038/s41586-021-03800-z},
year = {2021},
date = {2021-07-14},
journal = {Nature},
volume = {597},
pages = {114-118},
abstract = {In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide (CDN) 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases, present in both prokaryotes1 and eukaryotes2–5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as important regulators of phage infections6–8. Here, we identify two novel cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting and NF-κB dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by dsRNA to produce the novel CDN 3'2'-cGAMP whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2' cGAMP in response to a yet unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors sensing different types of nucleic acids and triggering immunity through production of CDNs beyond 2'3'-cGAMP.},
keywords = {antiviral immunity, cGAS-like receptors, Drosophila, imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Slavik Kailey M, Morehouse Benjamin R, Ragucci Adelyn E, Zhou Wen, Ai Xianlong, Chen Yuqiang, Li Lihua, Wei Ziming, Bähre Heike, König Martin, Seifert Roland, Lee Amy S Y, Cai Hua, Imler Jean-Luc, Kranzusch Philip J
cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila Article de journal
Dans: Nature, vol. 597, no. 7874, p. 109–113, 2021, ISSN: 1476-4687.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{pmid34261127,
title = {cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila},
author = {Kailey M Slavik and Benjamin R Morehouse and Adelyn E Ragucci and Wen Zhou and Xianlong Ai and Yuqiang Chen and Lihua Li and Ziming Wei and Heike Bähre and Martin König and Roland Seifert and Amy S Y Lee and Hua Cai and Jean-Luc Imler and Philip J Kranzusch},
doi = {10.1038/s41586-021-03743-5},
issn = {1476-4687},
year = {2021},
date = {2021-07-14},
journal = {Nature},
volume = {597},
number = {7874},
pages = {109--113},
abstract = {Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells. Animal genomes typically encode multiple proteins with predicted homology to cGAS, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Cai Hua, Imler Jean-Luc
cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette Article de journal
Dans: Faculty Reviews, vol. 10, p. 54, 2021.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{Cai2021,
title = {cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette},
author = {Hua Cai and Jean-Luc Imler
},
url = { https://doi.org/10.12703/r/10-54},
doi = {10.12703/r/10-54},
year = {2021},
date = {2021-06-08},
journal = {Faculty Reviews},
volume = {10},
pages = {54},
abstract = {Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway of innate immunity in mammals. It is activated upon binding the cyclic dinucleotide 2′3′-cGAMP, a second messenger produced by the enzyme cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), which acts as the receptor for DNA in this pathway, and triggers the expression of interferons and other viral stress-induced genes. The ancient origin of STING in the evolution of animals had been noted, but its primitive function was speculative. We review here recent advances in the remarkable history of cGAS-STING signaling, which establish that cGAS is a member of the family of cGAS/DncV-like nucleotidyltransferases (CD-NTases). In bacteria, CD-NTases synthesize a wide range of cyclic oligonucleotide second messengers in response to bacteriophage infections, which in turn activate a variety of effector proteins to abort phage infection. Among these effectors, some are related to STING, revealing an ancestral function for the cGAS-STING cassette in antiviral host defense. Study of STING signaling in invertebrate animals is consistent with an early acquisition in the history of metazoans of CD-NTase- and STING-encoding genes to counter the universal threat of viruses. In particular, STING-dependent immunity appears to play a previously unsuspected important role in some insects. These discoveries open up interesting perspectives for the use of model organisms to decipher emerging aspects of cGAS-STING biology in mammals, such as the activation of interferon-independent responses or the function and regulation of cGAS in the nucleus.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Leite Thiago H J F, Ferreira Alvaro G A, Imler Jean-Luc, Marques João T
Distinct Roles of Hemocytes at Different Stages of Infection by Dengue and Zika Viruses in Aedes aegypti Mosquitoes Article de journal
Dans: Frontiers in immunology, vol. 12, p. 660873, 2021.
Résumé | Liens | BibTeX | Étiquettes: Aedes, Dengue, Hemocytes, imler, innate immunity, M3i, Marques, Zika
@article{Leite2021,
title = {Distinct Roles of Hemocytes at Different Stages of Infection by Dengue and Zika Viruses in Aedes aegypti Mosquitoes},
author = {Thiago H J F Leite and Alvaro G A Ferreira and Jean-Luc Imler and João T Marques},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.660873/full},
doi = {10.3389/fimmu.2021.660873},
year = {2021},
date = {2021-05-13},
journal = {Frontiers in immunology},
volume = {12},
pages = {660873},
abstract = {Aedes aegypti mosquitoes are vectors for arboviruses of medical importance such as dengue (DENV) and Zika (ZIKV) viruses. Different innate immune pathways contribute to the control of arboviruses in the mosquito vector including RNA interference, Toll and Jak- STAT pathways. However, the role of cellular responses mediated by circulating macrophage-like cells known as hemocytes remains unclear. Here we show that hemocytes are recruited to the midgut of Ae. aegypti mosquitoes in response to DENV or ZIKV. Blockade of the phagocytic function of hemocytes using latex beads induced increased accumulation of hemocytes in the midgut and a reduction in virus infection levels in this organ. In contrast, inhibition of phagocytosis by hemocytes led to increased systemic dissemination and replication of DENV and ZIKV. Hence, our work reveals a dual role for hemocytes in Ae. aegypti mosquitoes, whereby phagocytosis is not required to control viral infection in the midgut but is essential to restrict systemic dissemination. Further understanding of the mechanism behind this duality could help the design of vector-based strategies to prevent transmission of arboviruses.},
keywords = {Aedes, Dengue, Hemocytes, imler, innate immunity, M3i, Marques, Zika},
pubstate = {published},
tppubtype = {article}
}
Jactel H, Imler JL, Lambrechts L, Failloux AB, Lebreton JD, Maho Y Le, Duplessy JC, Cossart P, Grandcolas P
Insect decline: immediate action is needed Article de journal
Dans: Comptes Rendus. Biologies, 2021, ISSN: 17683238.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{H2021,
title = {Insect decline: immediate action is needed},
author = {H Jactel and JL Imler and L Lambrechts and AB Failloux and JD Lebreton and Y Le Maho and JC Duplessy and P Cossart and P Grandcolas},
url = {https://doi.org/10.5802/crbiol.37},
doi = {10.5802/crbiol.37},
issn = {17683238},
year = {2021},
date = {2021-01-25},
journal = {Comptes Rendus. Biologies},
abstract = { Insects appeared more than 400 million years ago and they represent the richest and most diverse taxonomic group with several million species. Yet, under the combined effect of the loss of natural habitats, the intensification of agriculture with massive use of pesticides, global warming and biological invasions, insects show alarming signs of decline. Although difficult to quantify, species extinction and population reductions are confirmed for many ecosystems. This results in a loss of services such as the pollination of plants, including food crops, the recycling of organic matter, the supply of goods such as honey and the stability of food webs. It is therefore urgent to halt the decline of Insects. We recommend implementing long-term monitoring of populations, tackling the causes of insect decline by reducing the use of synthetic insecticides, preserving natural habitats, and reinventing a positive relationship between humans and insects.
Apparus il y a plus de 400 millions d’années, les Insectes représentent le groupe taxonomique le plus riche et diversifié, avec plusieurs millions d’espèces. Sous l’effet de la disparition des habitats, de l’intensification de l’agriculture avec l’usage massif des pesticides, du réchauffement climatique et des invasions biologiques, les Insectes montrent des signes alarmants de déclin. Bien que difficiles à quantifier, la disparition des espèces et la réduction de leurs populations sont avérées et communes à de nombreux écosystèmes. Elles se traduisent par une perte des services rendus, comme la pollinisa- tion des plantes vivrières, le recyclage de la matière organique, la fourniture de biens comme le miel, et l’équilibre des réseaux trophiques. Il est donc urgent de freiner le déclin des Insectes. Pour cela, il faut mettre en œuvre des suivis à long terme des populations, réduire l’usage des insecticides de syn- thèse, préserver les habitats naturels, et réinventer la relation de l’Homme à l’Insecte en revalorisant son image et ses usages.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Schneider J, Imler JL
Sensing and signalling viral infection in drosophila Article de journal
Dans: Developmental and Comparative Immunology, vol. 117, 2020.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{Schneider2020,
title = {Sensing and signalling viral infection in drosophila},
author = {J Schneider and JL Imler},
url = {https://doi.org/10.1016/j.dci.2020.103985
},
doi = {10.1016/j.dci.2020.103985},
year = {2020},
date = {2020-12-23},
journal = {Developmental and Comparative Immunology},
volume = {117},
abstract = {The fruitfly Drosophila melanogaster is a valuable model to unravel mechanisms of innate immunity, in particular in the context of viral infections. RNA interference, and more specifically the small interfering RNA pathway, is a major component of antiviral immunity in drosophila. In addition, the contribution of inducible transcriptional responses to the control of viruses in drosophila and other invertebrates is increasingly recognized. In particular, the recent discovery of a STING-IKKβ-Relish signalling cassette in drosophila has confirmed that NF-κB tran- scription factors play an important role in the control of viral infections, in addition to bacterial and fungal infections. Here, we review recent developments in the field, which begin to shed light on the mechanisms involved in sensing of viral infections and in signalling leading to production of antiviral effectors.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Cai H, Holleufer A, Simonsen B, Schneider J, Lemoine A, Gad HH, Huang J, Huang J, Chen D, Peng T, Marques JT, Hartmann R, Martins N, Imler JL
2'3'-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila Article de journal
Dans: Science Signaling, vol. 13, no. 660, p. eabc4537, 2020.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i, Marques, STING
@article{Cai_2020,
title = {2'3'-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila},
author = {H Cai and A Holleufer and B Simonsen and J Schneider and A Lemoine and HH Gad and J Huang and J Huang and D Chen and T Peng and JT Marques and R Hartmann and N Martins and JL Imler},
url = {https://pubmed.ncbi.nlm.nih.gov/33262294/},
doi = {10.1126/scisignal.abc4537 },
year = {2020},
date = {2020-12-01},
journal = {Science Signaling},
volume = {13},
number = {660},
pages = {eabc4537},
abstract = {We previously reported that an ortholog of STING regulates infection by picorna-like viruses in Drosophila In mammals, STING is activated by the cyclic dinucleotide 2'3'-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 2'3'-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 2'3'-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 2'3'-cGAMP-mediated protection was still observed in flies with mutations in Atg7 and AGO2, genes that encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, this protection was abrogated in flies with mutations in the gene encoding the NF-κB transcription factor Relish. Transcriptomic analysis of 2'3'-cGAMP-injected flies revealed a complex response pattern in which genes were rapidly induced, induced after a delay, or induced in a sustained manner. Our results reveal that dSTING regulates an NF-κB-dependent antiviral program that predates the emergence of interferons in vertebrates. },
keywords = {imler, M3i, Marques, STING},
pubstate = {published},
tppubtype = {article}
}
Imler JL, Hofmann JA
L'immunité innée Chapitre d'ouvrage
Dans: Cramer, P; Meignien, A (Ed.): vol. Le défi des maladies infectieuses, p. 191-203, Les éditions du Palais, Docis, 2020, ISBN: 9791090119895.
BibTeX | Étiquettes: hoffmann, imler, M3i
@inbook{Imler_2020,
title = {L'immunité innée},
author = {JL Imler and JA Hofmann},
editor = {P Cramer and A Meignien},
isbn = {9791090119895},
year = {2020},
date = {2020-11-30},
volume = {Le défi des maladies infectieuses},
pages = {191-203},
publisher = {Les éditions du Palais},
edition = {Docis},
keywords = {hoffmann, imler, M3i},
pubstate = {published},
tppubtype = {inbook}
}
Aguiar ERGR, de Almeida JPP, Queiroz LR, Oliveira LS, Olmo RP, de Faria IJDS, Imler JL, Gruber A, Matthews BJ, Marques JT
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 Article de journal
Dans: RNA, vol. 26, no. 5, p. 581-594, 2020.
Résumé | Liens | BibTeX | Étiquettes: 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}
}
Goto Akira, Okado Kiyoshi, Martins Nelson, Cai Hua, Barbier Vincent, Lamiable Olivier, Troxler Laurent, Santiago Estelle, Kuhn Lauriane, Paik Donggi, Silverman Neal, Holleufer Andreas, Hartmann Rune, Liu Jiyong, Peng Tao, Hoffmann Jules A, Meignin Carine, Daeffler Laurent, Imler Jean-Luc
The Kinase IKKβ Regulates a STING-and NF-κB-Dependent Antiviral Response Pathway in Drosophila Article de journal
Dans: Immunity, vol. 52, no. 1, p. 200, 2020.
Résumé | Liens | BibTeX | Étiquettes: antiviral, Drosophila, hoffmann, imler, Kinase, M3i, meignin, STING
@article{goto2020,
title = {The Kinase IKKβ Regulates a STING-and NF-κB-Dependent Antiviral Response Pathway in Drosophila},
author = {Akira Goto and Kiyoshi Okado and Nelson Martins and Hua Cai and Vincent Barbier and Olivier Lamiable and Laurent Troxler and Estelle Santiago and Lauriane Kuhn and Donggi Paik and Neal Silverman and Andreas Holleufer and Rune Hartmann and Jiyong Liu and Tao Peng and Jules A Hoffmann and Carine Meignin and Laurent Daeffler and Jean-Luc Imler
},
url = {https://www-sciencedirect-com.insb.bib.cnrs.fr/science/article/pii/S107476131930528X},
doi = {10.1016/j.immuni.2019.12.009 },
year = {2020},
date = {2020-01-14},
journal = {Immunity},
volume = {52},
number = {1},
pages = {200},
abstract = {Antiviral immunity inDrosophilainvolves RNA inter-ference and poorly characterized inducible re-sponses. Here, we showed that two components ofthe IMD pathway, the kinase dIKKband the tran-scription factor Relish, were required to controlinfection by two picorna-like viruses. We identifieda set of genes induced by viral infection and regu-lated by dIKKband Relish, which included an ortho-log of STING. We showed that dSTING participatedin the control of infection by picorna-like viruses,acting upstream of dIKKbto regulate expression ofNazo, an antiviral factor. Our data reveal an antiviralfunction for STING in an animal model devoid of inter-ferons and suggest an evolutionarily ancient role forthis molecule in antiviral immunity.},
keywords = {antiviral, Drosophila, hoffmann, imler, Kinase, M3i, meignin, STING},
pubstate = {published},
tppubtype = {article}
}
Talide L, Imler JL, Meignin C
Sensing Viral Infections in Insects: A Dearth of Pathway Receptors Article de journal
Dans: Curr Issues Mol Biol, vol. 34, p. 31-60, 2019, ISBN: 9781912530090.
Résumé | Liens | BibTeX | Étiquettes: imler, innate immunity, M3i, meignin, STAT, viral Infection
@article{Talide_2020,
title = {Sensing Viral Infections in Insects: A Dearth of Pathway Receptors},
author = {L Talide and JL Imler and C Meignin},
url = {https://www.caister.com/insectvirology2},
doi = {10.21775/cimb.034.031},
isbn = {9781912530090},
year = {2019},
date = {2019-06-06},
journal = {Curr Issues Mol Biol},
volume = {34},
pages = {31-60},
abstract = {Insects, the most diverse group of animals, can be infected by an extraordinary diversity of viruses. Among them, arthropod-borne viruses can be transmitted to humans, while bee and silkworm viruses cause important economic losses. Like all invertebrates, insects rely solely on innate immunity to counter viral infections. Protein-based mechanisms, involving restriction factors and evolutionarily conserved signaling pathways regulating transcription factors of the NF-kB and STAT families, participate in the control of viral infections in insects. In addition, RNA-based responses play a major role in the silencing of viral RNAs. We review here our current state of knowledge on insect antiviral defense mechanisms, which include conserved as well as adaptive, insect-specific strategies. Identification of the innate immunity receptors that sense viral infection in insects remains a major challenge for the field. },
keywords = {imler, innate immunity, M3i, meignin, STAT, viral Infection},
pubstate = {published},
tppubtype = {article}
}
Olmo RP, Martins NE, Aguiar ERGR, Marques JT, Imler JL
The insect reservoir of biodiversity for viruses and for antiviral mechanisms Article de journal
Dans: An Acad Bras Cienc , vol. 91, no. Suppl 3, p. e20190122, 2019.
Résumé | Liens | BibTeX | Étiquettes: 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}
}
Einhorn E., Imler JL
Insect Immunity: From Systemic to Chemosensory Organs Protection Chapitre d'ouvrage
Dans: Picimbon, JF (Ed.): vol. 2, p. 205-229, Springer, 2019, ISBN: 9783030051648.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@inbook{Einhorn_2019,
title = {Insect Immunity: From Systemic to Chemosensory Organs Protection},
author = {E. Einhorn and JL Imler},
editor = {JF Picimbon},
url = {https://link.springer.com/chapter/10.1007%2F978-3-030-05165-5_9},
isbn = {9783030051648},
year = {2019},
date = {2019-05-17},
volume = {2},
pages = {205-229},
publisher = {Springer},
abstract = {Insects are confronted to a wide range of infectious microorganisms. Tissues in direct contact with the environment, such as olfactory organs, are particularly exposed to pathogens. We review here the immune mechanisms operating in insects to control infections. Experiments conducted on the model organism Drosophila melanogaster (fruit fly) have provided genetic evidence that insects rely on both cellular and humoral mechanisms to control infections. Once epithelial barriers have been breached, circulating or membrane-associated innate immunity receptors trigger signaling in the fat body and lead to secretion of high concentrations of antimicrobial peptides active on fungi and bacteria in the hemolymph. This induced response involves the evolutionarily conserved Toll and immune deficiency (IMD) signaling pathways, which promote nuclear translocation of transcription factors of the NF-κB family. In addition, different subsets of differentiated blood cells or hemocytes can neutralize bacteria, fungi or parasites by phagocytosis, production of microbicidal compounds, or encapsulation. An alternative to mount costly immune responses is to sense pathogens through chemosensory cues and avoid them. Interestingly, some families of molecules, including the Toll receptors, participate in both olfaction and immunity.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {inbook}
}
Martins NE, Olmo RP, Aguiar ERGR, Marques JT, Imler JL
Les insectes : un fantastique réservoir de virus et de gènes antiviraux Article de journal
Dans: Biologie Aujourd'hui, vol. 212, no. 3-4, p. 101-106, 2019.
Résumé | Liens | BibTeX | Étiquettes: antiviral immunity, ARN interference, imler, Insect, M3i, Marques, metagenomic, virome
@article{Martins_2019jbio,
title = {Les insectes : un fantastique réservoir de virus et de gènes antiviraux},
author = {NE Martins and RP Olmo and ERGR Aguiar and JT Marques and JL Imler},
url = {https://www.biologie-journal.org/articles/jbio/abs/2018/02/jbio190008/jbio190008.html},
doi = {10.1051/jbio/2019008},
year = {2019},
date = {2019-04-11},
journal = {Biologie Aujourd'hui},
volume = {212},
number = {3-4},
pages = {101-106},
abstract = {Les insectes forment le groupe d’animaux qui présente la plus grande diversité. Des travaux récents de métagénomique montrent qu’ils peuvent être infectés par une diversité extraordinaire de virus. Parmi eux, les arbovirus (arthropod-borne viruses) peuvent être transmis à l’Homme par les insectes hématophages, notamment les moustiques. Le séquençage à haut débit des petits ARN des insectes fournit des informations sur leur virome, un paramètre qui pourrait contribuer à expliquer la dynamique de la transmission des maladies infectieuses par des insectes vecteurs. D’autre part, la caractérisation des mécanismes qui restreignent les infections virales chez les insectes révèle des innovations génétiques qui pourraient à terme inspirer de nouvelles stratégies antivirales.},
keywords = {antiviral immunity, ARN interference, imler, Insect, M3i, Marques, metagenomic, virome},
pubstate = {published},
tppubtype = {article}
}
Martins N, Lemoine A, Santiago E, Paro S, Imler JL, Meignin C
A Transgenic Flock House Virus Replicon Reveals an RNAi Independent Antiviral Mechanism Acting in Drosophila Follicular Somatic Cells Article de journal
Dans: G3 (Bethesda), vol. 9, no. 2, p. 403-412, 2019.
Liens | BibTeX | Étiquettes: antiviral immunity, Drosophila melanogaster, Follicular somatic cells, Genetics of Immunity, imler, M3i, meignin, replicon, Viral replicon
@article{Martins_2019i,
title = {A Transgenic Flock House Virus Replicon Reveals an RNAi Independent Antiviral Mechanism Acting in Drosophila Follicular Somatic Cells },
author = {N Martins and A Lemoine and E Santiago and S Paro and JL Imler and C Meignin},
url = {https://www.g3journal.org/content/9/2/403.long},
doi = {10.1534/g3.118.200872},
year = {2019},
date = {2019-02-07},
journal = { G3 (Bethesda)},
volume = {9},
number = {2},
pages = {403-412},
keywords = {antiviral immunity, Drosophila melanogaster, Follicular somatic cells, Genetics of Immunity, imler, M3i, meignin, replicon, Viral replicon},
pubstate = {published},
tppubtype = {article}
}
Olmo RP, Ferreira AGA, Izidoro-Toledo TC, Aguiar ERGR, de Faria IJS, de Souza KPR, Osório KP, Kuhn L, Hammann P, de Andrade EG, Todjro YM, Rocha MN, Leite THJF, Amadou SCG, Armache JN, Paro S, de Oliveira CD, Carvalho FD, Moreira LA, Marois E, Imler JL, Marques JT
Control of dengue virus in the midgut of Aedes aegypti by ectopic expression of the dsRNA-binding protein Loqs2 Article de journal
Dans: Nature Microbiology, vol. 3, no. 12, p. 1385-1393, 2018.
Résumé | Liens | BibTeX | Étiquettes: Aedes aegypti, Dengue, imler, M3i, marois, Marques, Zika
@article{Olmo_2018,
title = {Control of dengue virus in the midgut of Aedes aegypti by ectopic expression of the dsRNA-binding protein Loqs2 },
author = {RP Olmo and AGA Ferreira and TC Izidoro-Toledo and ERGR Aguiar and IJS de Faria and KPR de Souza and KP Osório and L Kuhn and P Hammann and EG de Andrade and YM Todjro and MN Rocha and THJF Leite and SCG Amadou and JN Armache and S Paro and CD de Oliveira and FD Carvalho and LA Moreira and E Marois and JL Imler and JT Marques},
url = {https://www.nature.com/articles/s41564-018-0268-6},
doi = {10.1038/s41564-018-0268-6},
year = {2018},
date = {2018-10-29},
journal = {Nature Microbiology},
volume = {3},
number = {12},
pages = {1385-1393},
abstract = {Dengue virus (DENV) is an arbovirus transmitted to humans by Aedes mosquitoes. In the insect vector, the small interfering RNA (siRNA) pathway is an important antiviral mechanism against DENV. However, it remains unclear when and where the siRNA pathway acts during the virus cycle. Here, we show that the siRNA pathway fails to efficiently silence DENV in the midgut of Aedes aegypti although it is essential to restrict systemic replication. Accumulation of DENV-derived siRNAs in the midgut reveals that impaired silencing results from a defect downstream of small RNA biogenesis. Notably, silencing triggered by endogenous and exogenous dsRNAs remained effective in the midgut where known components of the siRNA pathway, including the double-stranded RNA (dsRNA)-binding proteins Loquacious and r2d2, had normal expression levels. We identified an Aedes-specific paralogue of loquacious and r2d2, hereafter named loqs2, which is not expressed in the midgut. Loqs2 interacts with Loquacious and r2d2 and is required to control systemic replication of DENV and also Zika virus. Furthermore, ectopic expression of Loqs2 in the midgut of transgenic mosquitoes is sufficient to restrict DENV replication and dissemination. Together, our data reveal a mechanism of tissue-specific regulation of the mosquito siRNA pathway controlled by Loqs2. },
keywords = {Aedes aegypti, Dengue, imler, M3i, marois, Marques, Zika},
pubstate = {published},
tppubtype = {article}
}
Goto Akira, Okado Kiyoshi, Martins Nelson, Cai Hua, Barbier Vincent, Lamiable Olivier, Troxler Laurent, Santiago Estelle, Kuhn Lauriane, Paik Donggi, Silverman Neal, Holleufer Andreas, Hartmann Rune, Liu Jiyong, Peng Tao, Hoffmann Jules A, Meignin Carine, Daeffler Laurent, Imler Jean-Luc
The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila Article de journal
Dans: Immunity, no. 49, p. 225-234, 2018.
Résumé | Liens | BibTeX | Étiquettes: hoffmann, imler, M3i, meignin, PPSE
@article{Goto2018,
title = {The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila},
author = {Akira Goto and Kiyoshi Okado and Nelson Martins and Hua Cai and Vincent Barbier and Olivier Lamiable and Laurent Troxler and Estelle Santiago and Lauriane Kuhn and Donggi Paik and Neal Silverman and Andreas Holleufer and Rune Hartmann and Jiyong Liu and Tao Peng and Jules A Hoffmann and Carine Meignin and Laurent Daeffler and Jean-Luc Imler},
editor = {Elsevier Inc.},
url = {https://doi.org/10.1016/j.immuni.2018.07.013},
doi = {j.immuni.2018.07.013},
year = {2018},
date = {2018-08-21},
journal = {Immunity},
number = {49},
pages = {225-234},
abstract = {Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity.},
keywords = {hoffmann, imler, M3i, meignin, PPSE},
pubstate = {published},
tppubtype = {article}
}
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 Article de journal
Dans: PLoS Negl Trop Dis, vol. 12, no. 6, p. e0006569, 2018, ISSN: 1935-2735.
Résumé | Liens | BibTeX | Étiquettes: 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}
}
Kuhn Lauriane, Majzoub Karim, Einhorn Evelyne, Chicher Johana, Pompon Julien, Imler Jean-Luc, Hammann Philippe, Meignin Carine
Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS Article de journal
Dans: G3 (Bethesda), 2017, ISSN: 2160-1836.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i, meignin, PPSE
@article{kuhn_definition_2017,
title = {Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS},
author = {Lauriane Kuhn and Karim Majzoub and Evelyne Einhorn and Johana Chicher and Julien Pompon and Jean-Luc Imler and Philippe Hammann and Carine Meignin},
doi = {10.1534/g3.117.042564},
issn = {2160-1836},
year = {2017},
date = {2017-12-31},
journal = {G3 (Bethesda)},
abstract = {Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus, an IRES-containing virus.},
keywords = {imler, M3i, meignin, PPSE},
pubstate = {published},
tppubtype = {article}
}
Gross E, Vincens Q, Einhorn E, Noireterre A, Schaeffer L, Kuhn L, Imler JL, Eriani, Meignin C, Martin F
The IRES5'UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure Article de journal
Dans: Nucleic Acids Research, vol. 45, no. 15, p. 8993-9004, 2017.
Résumé | Liens | BibTeX | Étiquettes: imler, IRES, M3i, meignin
@article{Gross_2017,
title = {The IRES5'UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure},
author = {E Gross and Q Vincens and E Einhorn and A Noireterre and L Schaeffer and L Kuhn and JL Imler and Eriani and C Meignin and F Martin},
url = {https://academic.oup.com/nar/article/45/15/8993/3978035},
doi = {10.1093/nar/gkx622 },
year = {2017},
date = {2017-09-06},
journal = {Nucleic Acids Research},
volume = {45},
number = {15},
pages = {8993-9004},
abstract = {Cricket paralysis virus (CrPV) is a dicistrovirus. Its positive-sense single-stranded RNA genome contains two internal ribosomal entry sites (IRESs). The 5' untranslated region (5'UTR) IRES5'UTR mediates translation of non-structural proteins encoded by ORF1 whereas the well-known intergenic region (IGR) IRESIGR is required for translation of structural proteins from open reading frame 2 in the late phase of infection. Concerted action of both IRES is essential for host translation shut-off and viral translation. IRESIGR has been extensively studied, in contrast the IRES5'UTR remains largely unexplored. Here, we define the minimal IRES element required for efficient translation initiation in drosophila S2 cell-free extracts. We show that IRES5'UTR promotes direct recruitment of the ribosome on the cognate viral AUG start codon without any scanning step, using a Hepatitis-C virus-related translation initiation mechanism. Mass spectrometry analysis revealed that IRES5'UTR recruits eukaryotic initiation factor 3, confirming that it belongs to type III class of IRES elements. Using Selective 2'-hydroxyl acylation analyzed by primer extension and DMS probing, we established a secondary structure model of 5'UTR and of the minimal IRES5'UTR. The IRES5'UTR contains a pseudoknot structure that is essential for proper folding and ribosome recruitment. Overall, our results pave the way for studies addressing the synergy and interplay between the two IRES from CrPV. },
keywords = {imler, IRES, M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
FM Cao C Cogni R Barbier V Jiggins
Complex Coding and Regulatory Polymorphisms in a Restriction Factor Determine the Susceptibility of Drosophila to Viral Infection Article de journal
Dans: Genetics, vol. 206, p. 2159-2173, 2017.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{FM2017,
title = {Complex Coding and Regulatory Polymorphisms in a Restriction Factor Determine the Susceptibility of Drosophila to Viral Infection},
author = {Cao C
Cogni R
Barbier V
Jiggins FM},
url = {https://academic.oup.com/genetics/article/206/4/2159/6072650},
doi = {10.1534/genetics.117.201970},
year = {2017},
date = {2017-06-19},
journal = {Genetics},
volume = {206},
pages = {2159-2173},
abstract = {It is common to find that major-effect genes are an important cause of variation in susceptibility to infection. Here we have characterized natural variation in a gene called pastrel that explains over half of the genetic variance in susceptibility to the Drosophila C virus (DCV) in populations of Drosophila melanogaster. We found extensive allelic heterogeneity, with a sample of seven alleles of pastrel from around the world conferring four phenotypically distinct levels of resistance. By modifying candidate SNPs in transgenic flies, we show that the largest effect is caused by an amino acid polymorphism that arose when an ancestral threonine was mutated to alanine, greatly increasing resistance to DCV. Overexpression of the ancestral, susceptible allele provides strong protection against DCV; indicating that this mutation acted to improve an existing restriction factor. The pastrel locus also contains complex structural variation and cis-regulatory polymorphisms altering gene expression. We find that higher expression of pastrel is associated with increased survival after DCV infection. To understand why this variation is maintained in populations, we investigated genetic variation surrounding the amino acid variant that is causing flies to be resistant. We found no evidence of natural selection causing either recent changes in allele frequency or geographical variation in frequency, suggesting that this is an old polymorphism that has been maintained at a stable frequency. Overall, our data demonstrate how complex genetic variation at a single locus can control susceptibility to a virulent natural pathogen.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Mussabekova Assel, Daeffler Laurent, Imler Jean-Luc
Innate and intrinsic antiviral immunity in Drosophila Article de journal
Dans: Cell. Mol. Life Sci., 2017, ISSN: 1420-9071.
Résumé | Liens | BibTeX | Étiquettes: Argonaute 2, Dicer-2, IMD pathway, imler, Jak/STAT pathway, M3i, NF-κB
@article{mussabekova_innate_2017,
title = {Innate and intrinsic antiviral immunity in Drosophila},
author = {Assel Mussabekova and Laurent Daeffler and Jean-Luc Imler},
doi = {10.1007/s00018-017-2453-9},
issn = {1420-9071},
year = {2017},
date = {2017-01-01},
journal = {Cell. Mol. Life Sci.},
abstract = {The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.},
keywords = {Argonaute 2, Dicer-2, IMD pathway, imler, Jak/STAT pathway, M3i, NF-κB},
pubstate = {published},
tppubtype = {article}
}
Paro Simona, Imler Jean-Luc
Encyclopedia of Immunobiology Chapitre d'ouvrage
Dans: Ratcliffe, M (Ed.): vol. 1, Chapitre “Immunity in insects”, p. 454-461, Elsevier, 2016.
BibTeX | Étiquettes: imler, Immunity, Insect, M3i
@inbook{Paro0000,
title = {Encyclopedia of Immunobiology},
author = {Simona Paro and Jean-Luc Imler},
editor = {M Ratcliffe},
year = {2016},
date = {2016-08-01},
volume = {1},
pages = {454-461},
publisher = {Elsevier},
chapter = {“Immunity in insects”},
keywords = {imler, Immunity, Insect, M3i},
pubstate = {published},
tppubtype = {inbook}
}
Lamiable Olivier, Kellenberger Christine, Kemp Cordula, Troxler Laurent, Pelte Nadège, Boutros Michael, Marques Joao Trindade, Daeffler Laurent, Hoffmann Jules A, Roussel Alain, Imler Jean-Luc
Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila Article de journal
Dans: PNAS, vol. 113, no. 3, p. 698–703, 2016, ISSN: 0027-8424, 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: antiviral immunity, bioinformatic, cytokine, Edin, hoffmann, imler, M3i, Sindbis Virus, virokine
@article{lamiable_cytokine_2016,
title = {Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila},
author = {Olivier Lamiable and Christine Kellenberger and Cordula Kemp and Laurent Troxler and Nadège Pelte and Michael Boutros and Joao Trindade Marques and Laurent Daeffler and Jules A Hoffmann and Alain Roussel and Jean-Luc Imler},
url = {http://www.pnas.org/content/113/3/698.abstract},
doi = {10.1073/pnas.1516122113},
issn = {0027-8424, 1091-6490},
year = {2016},
date = {2016-01-19},
urldate = {2016-01-07},
journal = {PNAS},
volume = {113},
number = {3},
pages = {698–703},
abstract = {Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.},
keywords = {antiviral immunity, bioinformatic, cytokine, Edin, hoffmann, imler, M3i, Sindbis Virus, virokine},
pubstate = {published},
tppubtype = {article}
}
Lamiable Olivier, Arnold Johan, da de Faria Isaque Joao Silva, Olmo Roenick Proveti, Bergami Francesco, Meignin Carine, Hoffmann Jules A, Marques Joao Trindade, Imler Jean-Luc
Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity Article de journal
Dans: J. Virol., vol. 90, no. 11, p. 5415–5426, 2016, ISSN: 0022-538X, 1098-5514.
Liens | BibTeX | Étiquettes: antiviral immunity, Autophagy, Hemocytes, hoffmann, imler, M3i, meignin
@article{lamiable_analysis_2016,
title = {Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity},
author = {Olivier Lamiable and Johan Arnold and Isaque Joao Silva da de Faria and Roenick Proveti Olmo and Francesco Bergami and Carine Meignin and Jules A Hoffmann and Joao Trindade Marques and Jean-Luc Imler},
url = {http://jvi.asm.org/content/90/11/5415},
doi = {10.1128/JVI.00238-16},
issn = {0022-538X, 1098-5514},
year = {2016},
date = {2016-01-01},
urldate = {2016-06-05},
journal = {J. Virol.},
volume = {90},
number = {11},
pages = {5415--5426},
keywords = {antiviral immunity, Autophagy, Hemocytes, hoffmann, imler, M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
Marques João T, Imler Jean-Luc
The diversity of insect antiviral immunity: insights from viruses Article de journal
Dans: Current Opinion in Microbiology, vol. 32, p. 71–76, 2016, ISSN: 1369-5274.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{marques_diversity_2016,
title = {The diversity of insect antiviral immunity: insights from viruses},
author = {João T Marques and Jean-Luc Imler},
url = {http://www.sciencedirect.com/science/article/pii/S1369527416300571},
doi = {10.1016/j.mib.2016.05.002},
issn = {1369-5274},
year = {2016},
date = {2016-01-01},
urldate = {2016-06-05},
journal = {Current Opinion in Microbiology},
volume = {32},
pages = {71--76},
abstract = {Insects represent over 70% of all animal species. Recent virome analyses reveal unprecedented genetic diversity of insect viruses, which appears to match that of their hosts. Thus, insect-virus interactions may provide information on a vast repertoire of antiviral immune mechanisms. Tapping into this diversity is challenging because of several constraints imposed by the uniqueness of each insect model. Nevertheless, it is clear that many conserved and divergent pathways participate in the control of viral infection in insects. Co-evolution between hosts and viruses favors the development of immune evasion mechanisms by the pathogen. Viral suppressors can offer unique perspective on host pathways and emphasize the importance of RNA interference, apoptosis, but also NF-κB pathways and translation control in insect antiviral immunity.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Martins Nelson, Imler Jean-Luc, Meignin Carine
Discovery of novel targets for antivirals: learning from flies Article de journal
Dans: Curr Opin Virol, vol. 20, p. 64–70, 2016, ISSN: 1879-6265.
Résumé | Liens | BibTeX | Étiquettes: antiviral, imler, M3i, meignin, target
@article{martins_discovery_2016,
title = {Discovery of novel targets for antivirals: learning from flies},
author = {Nelson Martins and Jean-Luc Imler and Carine Meignin},
url = {http://www.sciencedirect.com/science/article/pii/S1879625716301274},
doi = {10.1016/j.coviro.2016.09.005},
issn = {1879-6265},
year = {2016},
date = {2016-01-01},
journal = {Curr Opin Virol},
volume = {20},
pages = {64--70},
abstract = {Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals. In addition, functional screens revealed conserved host factors required for efficient viral translation, such as the ribosomal protein RACK1 and the release factor Pelo. These proteins are promising candidates for host-targeted antivirals.},
keywords = {antiviral, imler, M3i, meignin, target},
pubstate = {published},
tppubtype = {article}
}
Lamiable Olivier, Meignin Carine, Imler Jean-Luc
WntD and Diedel: Two immunomodulatory cytokines in Drosophila immunity Article de journal
Dans: Fly (Austin), vol. 10, no. 4, p. 187–194, 2016, ISSN: 1933-6942.
Résumé | Liens | BibTeX | Étiquettes: Cytokines, Drosophila, IMD pathway, imler, innate immunity, M3i, meignin, virus
@article{lamiable_wntd_2016,
title = {WntD and Diedel: Two immunomodulatory cytokines in Drosophila immunity},
author = {Olivier Lamiable and Carine Meignin and Jean-Luc Imler},
url = {http://www.tandfonline.com/doi/abs/10.1080/19336934.2016.1202387?journalCode=kfly20},
doi = {10.1080/19336934.2016.1202387},
issn = {1933-6942},
year = {2016},
date = {2016-01-01},
journal = {Fly (Austin)},
volume = {10},
number = {4},
pages = {187--194},
abstract = {Remarkable progress has been made on the understanding of the basic mechanisms of innate immunity in flies, from sensing infection to production of effector molecules. However, how the immune response is orchestrated at the level of the organism remains poorly understood. While cytokines activating immune responses, such as Spaetzle or Unpaired-3, have been identified and characterized in Drosophila, much less is known regarding immunosuppressor cytokines. In a recent publication, we reported the identification of a novel cytokine, Diedel, which acts as systemic negative regulator of the IMD pathway. Here, we discuss the similarities between Diedel and WntD, another immunomodulatory cytokine and present evidence that the 2 molecules act independently from one another.},
keywords = {Cytokines, Drosophila, IMD pathway, imler, innate immunity, M3i, meignin, virus},
pubstate = {published},
tppubtype = {article}
}
Aguiar Eric Roberto Guimarães Rocha, Olmo Roenick Proveti, Paro Simona, Ferreira Flavia Viana, da de Faria Isaque João Silva, Todjro Yaovi Mathias Honore, Lobo Francisco Pereira, Kroon Erna Geessien, Meignin Carine, Gatherer Derek, Imler Jean-Luc, Marques João Trindade
Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host Article de journal
Dans: Nucleic Acids Research, vol. 43, no. 13, p. 6191–6206, 2015, ISSN: 1362-4962.
Résumé | Liens | BibTeX | Étiquettes: Animals, Contig Mapping, Female, imler, insects, M3i, meignin, Ovary, Plants, RNA, Sequence Analysis, Small Untranslated, Vertebrates, Viral, Viral Tropism, viruses
@article{aguiar_sequence-independent_2015,
title = {Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host},
author = {Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Simona Paro and Flavia Viana Ferreira and Isaque João Silva da de Faria and Yaovi Mathias Honore Todjro and Francisco Pereira Lobo and Erna Geessien Kroon and Carine Meignin and Derek Gatherer and Jean-Luc Imler and João Trindade Marques},
url = {http://nar.oxfordjournals.org/lookup/doi/10.1093/nar/gkv587},
doi = {10.1093/nar/gkv587},
issn = {1362-4962},
year = {2015},
date = {2015-07-01},
journal = {Nucleic Acids Research},
volume = {43},
number = {13},
pages = {6191--6206},
abstract = {Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.},
keywords = {Animals, Contig Mapping, Female, imler, insects, M3i, meignin, Ovary, Plants, RNA, Sequence Analysis, Small Untranslated, Vertebrates, Viral, Viral Tropism, viruses},
pubstate = {published},
tppubtype = {article}
}
Majzoub Karim, Imler Jean-Luc
Encyclopedia of Molecular Cell Biology and Molecular Medicine Chapitre d'ouvrage
Dans: Verlag, Wiley-VCH (Ed.): vol. 1, Chapitre « RNAi to treat virus infections », p. 192-228, GmbH & Co. KGaA, 2015.
Résumé | Liens | BibTeX | Étiquettes: antiviral, Argonaute, Delivery, imler, Immunity, lipofection, M3i, microRNA (miRNA), RNA Virus Infections, RNAi, small hairpin RNA (shRNA), small interfering RNA (siRNA)
@inbook{Majzoub2015,
title = {Encyclopedia of Molecular Cell Biology and Molecular Medicine},
author = {Karim Majzoub and Jean-Luc Imler},
editor = {Wiley-VCH Verlag},
doi = {10.1002/3527600906.mcb.201500003},
year = {2015},
date = {2015-04-28},
volume = {1},
pages = {192-228},
publisher = {GmbH & Co. KGaA},
chapter = {« RNAi to treat virus infections »},
abstract = {In spite of its young age, the field of RNA interference has already yielded major advances in the laboratory. This sequence-specific mechanism of gene regulation also holds strong promise for the development of a new generation of drugs, in particular to control the everlasting threat of viral infections. Here, the mechanisms and pathways of RNA interference are reviewed, with emphasis placed on how RNA silencing forms a potent antiviral immune mechanism in plants and invertebrates. The approaches developed to use RNA interference to control viral infections in mammals are then described. Finally, the problems encountered while translating this revolutionary technology into the clinic are presented, and the advances currently developed to overcome these limitations are discussed.},
keywords = {antiviral, Argonaute, Delivery, imler, Immunity, lipofection, M3i, microRNA (miRNA), RNA Virus Infections, RNAi, small hairpin RNA (shRNA), small interfering RNA (siRNA)},
pubstate = {published},
tppubtype = {inbook}
}
Paro Simona, Imler Jean-Luc, Meignin Carine
Sensing viral RNAs by Dicer/RIG-I like ATPases across species Article de journal
Dans: Current Opinion in Immunology, vol. 32, p. 106–113, 2015, ISSN: 1879-0372.
Résumé | Liens | BibTeX | Étiquettes: Adenosine Triphosphatases, Animals, DEAD-box RNA Helicases, Humans, imler, M3i, meignin, Protein Binding, Protein Interaction Domains and Motifs, Ribonuclease III, RNA, Viral, Virus Diseases, viruses
@article{paro_sensing_2015,
title = {Sensing viral RNAs by Dicer/RIG-I like ATPases across species},
author = {Simona Paro and Jean-Luc Imler and Carine Meignin},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0952791515000102},
doi = {10.1016/j.coi.2015.01.009},
issn = {1879-0372},
year = {2015},
date = {2015-02-01},
journal = {Current Opinion in Immunology},
volume = {32},
pages = {106--113},
abstract = {Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical studies on the function and regulation of DRAs reveal similarities, but also some differences, between viral RNA sensing mechanisms in nematodes, flies and mammals.},
keywords = {Adenosine Triphosphatases, Animals, DEAD-box RNA Helicases, Humans, imler, M3i, meignin, Protein Binding, Protein Interaction Domains and Motifs, Ribonuclease III, RNA, Viral, Virus Diseases, viruses},
pubstate = {published},
tppubtype = {article}
}
Chtarbanova Stanislava, Lamiable Olivier, Lee Kwang-Zin, Galiana Delphine, Troxler Laurent, Meignin Carine, Hetru Charles, Hoffmann Jules A, Daeffler Laurent, Imler Jean-Luc
Drosophila C virus systemic infection leads to intestinal obstruction Article de journal
Dans: Journal of Virology, vol. 88, no. 24, p. 14057–14069, 2014, ISSN: 1098-5514.
Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Dicistroviridae, Female, Gastrointestinal Tract, Gene Expression Profiling, hoffmann, imler, Intestinal Obstruction, M3i, meignin, Muscle, Nodaviridae, Sindbis Virus, Smooth, Viral Tropism
@article{chtarbanova_drosophila_2014,
title = {Drosophila C virus systemic infection leads to intestinal obstruction},
author = {Stanislava Chtarbanova and Olivier Lamiable and Kwang-Zin Lee and Delphine Galiana and Laurent Troxler and Carine Meignin and Charles Hetru and Jules A Hoffmann and Laurent Daeffler and Jean-Luc Imler},
url = {http://jvi.asm.org/content/88/24/14057},
doi = {10.1128/JVI.02320-14},
issn = {1098-5514},
year = {2014},
date = {2014-12-01},
journal = {Journal of Virology},
volume = {88},
number = {24},
pages = {14057--14069},
abstract = {Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCE: DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the tropism of the virus for an essential but poorly characterized organ in the digestive tract, the crop. Our results may have relevance for other members of the Dicistroviridae, some of which are pathogenic to beneficial or pest insect species.},
keywords = {Animals, bioinformatic, Dicistroviridae, Female, Gastrointestinal Tract, Gene Expression Profiling, hoffmann, imler, Intestinal Obstruction, M3i, meignin, Muscle, Nodaviridae, Sindbis Virus, Smooth, Viral Tropism},
pubstate = {published},
tppubtype = {article}
}
Lamiable Olivier, Imler Jean-Luc
Induced antiviral innate immunity in Drosophila Article de journal
Dans: Current Opinion in Microbiology, vol. 20, p. 62–68, 2014, ISSN: 1879-0364.
Résumé | Liens | BibTeX | Étiquettes: Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction
@article{lamiable_induced_2014,
title = {Induced antiviral innate immunity in Drosophila},
author = {Olivier Lamiable and Jean-Luc Imler},
doi = {10.1016/j.mib.2014.05.006},
issn = {1879-0364},
year = {2014},
date = {2014-08-01},
journal = {Current Opinion in Microbiology},
volume = {20},
pages = {62--68},
abstract = {Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals.},
keywords = {Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Goto Akira, Fukuyama Hidehiro, Imler Jean-Luc, Hoffmann Jules A
The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response Article de journal
Dans: The Journal of Biological Chemistry, vol. 289, no. 30, p. 20470–20476, 2014, ISSN: 1083-351X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors
@article{goto_chromatin_2014,
title = {The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response},
author = {Akira Goto and Hidehiro Fukuyama and Jean-Luc Imler and Jules A Hoffmann},
doi = {10.1074/jbc.C114.553719},
issn = {1083-351X},
year = {2014},
date = {2014-07-01},
journal = {The Journal of Biological Chemistry},
volume = {289},
number = {30},
pages = {20470--20476},
abstract = {The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.},
keywords = {Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Hoffmann Jules A
Le défi des maladies infectieuses Chapitre d'ouvrage
Dans: collection Guérir et prévenir demain, Ph. Cramer (Ed.): Chapitre « L’immunité innée », p. 167-174, Editions DOCIS, 2014, ISBN: 978-2-85525-390-9.
Résumé | BibTeX | Étiquettes: hoffmann, imler, innate immunity, M3i, maladies infectieuses
@inbook{Imler2014,
title = {Le défi des maladies infectieuses},
author = {Jean-Luc Imler and Jules A Hoffmann},
editor = {Ph. Cramer collection Guérir et prévenir demain},
isbn = {978-2-85525-390-9},
year = {2014},
date = {2014-06-01},
pages = {167-174},
publisher = {Editions DOCIS},
chapter = {« L’immunité innée »},
abstract = {La lèpre fait des ravages dès l’Antiquité, les épidémies de peste tuent au Moyen Âge et celles de choléra dévastent l’Inde. La tuberculose émerge véritablement au XIXème siècle, la grippe espagnole a fait vingt millions de morts en 1918 et de nouvelles maladies apparaissent : les infections hospitalières, les hépatites, le SIDA, les fièvres hémorragiques, la légionellose,…
Toutes ces maladies ont un point commun, ce sont des maladies infectieuses qui sont pour la médecine un vrai défi, tant elles sont dévastatrices. L’innovation a eu et continue à avoir un rôle essentiel dans la caractérisation de ces maladies, la découverte de l’agent responsable, leur traitement et leur prévention. Ce livre, dont les auteurs font partie des plus éminents spécialistes français et européens des maladies infectieuses décrit, de façon abordable par tous, aussi bien les découvertes et les inventions essentielles à ce domaine que les avancées médicales.},
keywords = {hoffmann, imler, innate immunity, M3i, maladies infectieuses},
pubstate = {published},
tppubtype = {inbook}
}
Imler Jean-Luc
Overview of Drosophila immunity: a historical perspective Article de journal
Dans: Developmental and Comparative Immunology, vol. 42, no. 1, p. 3–15, 2014, ISSN: 1879-0089.
Résumé | Liens | BibTeX | Étiquettes: Allergy and Immunology, Animal, Animals, Antimicrobial Cationic Peptides, Antimicrobial peptides, history, Humans, IMD pathway, imler, Immunity, Innate, innate immunity, M3i, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors
@article{imler_overview_2014,
title = {Overview of Drosophila immunity: a historical perspective},
author = {Jean-Luc Imler},
doi = {10.1016/j.dci.2013.08.018},
issn = {1879-0089},
year = {2014},
date = {2014-01-01},
journal = {Developmental and Comparative Immunology},
volume = {42},
number = {1},
pages = {3--15},
abstract = {The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30 years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field.},
keywords = {Allergy and Immunology, Animal, Animals, Antimicrobial Cationic Peptides, Antimicrobial peptides, history, Humans, IMD pathway, imler, Immunity, Innate, innate immunity, M3i, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Majzoub K, Hafirassou M L, Meignin C, Goto A, Marzi S, Fedorova A, Verdier Y, Vinh J, Hoffmann J A, Martin F, Baumert T F, Schuster C, Imler JL
RACK1 Controls IRES-Mediated Translation of Viruses. Article de journal
Dans: Cell, vol. 159, no. 5, p. 1086-1095, 2014, ISBN: 25416947.
Résumé | Liens | BibTeX | Étiquettes: ERIANI, hoffmann, imler, M3i, meignin, ROMBY, Unité ARN
@article{,
title = {RACK1 Controls IRES-Mediated Translation of Viruses.},
author = {K Majzoub and M L Hafirassou and C Meignin and A Goto and S Marzi and A Fedorova and Y Verdier and J Vinh and J A Hoffmann and F Martin and T F Baumert and C Schuster and JL Imler},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25416947},
doi = {10.1016/j.cell.2014.10.041},
isbn = {25416947},
year = {2014},
date = {2014-01-01},
journal = {Cell},
volume = {159},
number = {5},
pages = {1086-1095},
abstract = {Fighting viral infections is hampered by the scarcity of viral targets and their variability, resulting in development of resistance. Viruses depend on cellular molecules-which are attractive alternative targets-for their life cycle, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection, indicating that its function is conserved for distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a target for the development of broad antiviral intervention.},
keywords = {ERIANI, hoffmann, imler, M3i, meignin, ROMBY, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Petrillo Jessica E, Venter Arno P, Short James R, Gopal Radhika, Deddouche Safia, Lamiable Olivier, Imler Jean-Luc, Schneemann Anette
Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2 Article de journal
Dans: Journal of Virology, vol. 87, no. 24, p. 13409–13421, 2013, ISSN: 1098-5514.
Résumé | Liens | BibTeX | Étiquettes: Animals, Capsid Proteins, Cell Line, Cricetinae, Cytoplasmic Granules, Double-Stranded, imler, M3i, Nodaviridae, Protein Biosynthesis, RNA, RNA Virus Infections, RNA-Binding Proteins, Viral, Viral Proteins
@article{petrillo_cytoplasmic_2013,
title = {Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2},
author = {Jessica E Petrillo and Arno P Venter and James R Short and Radhika Gopal and Safia Deddouche and Olivier Lamiable and Jean-Luc Imler and Anette Schneemann},
doi = {10.1128/JVI.02362-13},
issn = {1098-5514},
year = {2013},
date = {2013-12-01},
journal = {Journal of Virology},
volume = {87},
number = {24},
pages = {13409--13421},
abstract = {Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is conveniently propagated in Drosophila melanogaster cells but can also be grown in mammalian cells. It was previously reported that B2 is dispensable for FHV RNA replication in BHK21 cells; therefore, we chose this cell line to generate a viral mutant that lacked the ability to produce B2. Consistent with published results, we found that RNA replication was indeed vigorous but the yield of progeny virus was negligible. Closer inspection revealed that infected cells contained very small amounts of coat protein despite an abundance of RNA2. B2 mutants that had reduced affinity for dsRNA produced analogous results, suggesting that the dsRNA binding capacity of B2 somehow played a role in coat protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we discovered that RNA2 is recruited into large cytoplasmic granules in the absence of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude that B2, by binding to double-stranded regions in progeny RNA2, prevents recruitment of RNA2 into cellular structures, where it is translationally silenced. This represents a novel function of B2 that further contributes to successful completion of the nodaviral life cycle.},
keywords = {Animals, Capsid Proteins, Cell Line, Cricetinae, Cytoplasmic Granules, Double-Stranded, imler, M3i, Nodaviridae, Protein Biosynthesis, RNA, RNA Virus Infections, RNA-Binding Proteins, Viral, Viral Proteins},
pubstate = {published},
tppubtype = {article}
}
Ezekowitz Alan R B, Dimarcq Jean-Luc, Kafatos Fotis, Levashina Elena A, Ferrandon Dominique, Hetru Charles, Imler Jean-Luc, Reichhart Jean-Marc
Lawrence's book review unfair to Hoffmann Article de journal
Dans: Curr. Biol., vol. 22, no. 12, p. R482, 2012, ISSN: 1879-0445.
Liens | BibTeX | Étiquettes: Book Reviews as Topic, Ethics, ferrandon, imler, M3i, Professional, reichhart
@article{ezekowitz_lawrences_2012,
title = {Lawrence's book review unfair to Hoffmann},
author = {Alan R B Ezekowitz and Jean-Luc Dimarcq and Fotis Kafatos and Elena A Levashina and Dominique Ferrandon and Charles Hetru and Jean-Luc Imler and Jean-Marc Reichhart},
doi = {10.1016/j.cub.2012.05.015},
issn = {1879-0445},
year = {2012},
date = {2012-06-01},
journal = {Curr. Biol.},
volume = {22},
number = {12},
pages = {R482},
keywords = {Book Reviews as Topic, Ethics, ferrandon, imler, M3i, Professional, reichhart},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Hoffmann Jules A
Nucleic Acid Sensors and Antiviral Immunity Chapitre d'ouvrage
Dans: eds T. Fujita & P. Sambhara, (Ed.): Chapitre 1 : Antiviral responses in invertebrates, p. 1-18, Landes Bioscience, 2012.
BibTeX | Étiquettes: antiviral immunity, hoffmann, imler, Invertebrate, M3i
@inbook{Imler2012,
title = {Nucleic Acid Sensors and Antiviral Immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
editor = {eds T. Fujita & P. Sambhara},
year = {2012},
date = {2012-06-01},
pages = {1-18},
publisher = {Landes Bioscience},
chapter = {1 : Antiviral responses in invertebrates},
keywords = {antiviral immunity, hoffmann, imler, Invertebrate, M3i},
pubstate = {published},
tppubtype = {inbook}
}
Goto Akira, Imler Jean-Luc
Toll signaling in flies and mammals: two sorts of MyD88 Article de journal
Dans: Immunity, vol. 36, no. 4, p. 555–557, 2012, ISSN: 1097-4180.
Résumé | Liens | BibTeX | Étiquettes: imler, M3i
@article{goto_toll_2012,
title = {Toll signaling in flies and mammals: two sorts of MyD88},
author = {Akira Goto and Jean-Luc Imler},
doi = {10.1016/j.immuni.2012.04.001},
issn = {1097-4180},
year = {2012},
date = {2012-04-01},
journal = {Immunity},
volume = {36},
number = {4},
pages = {555--557},
abstract = {The mammalian MyD88 signaling molecule participates in Toll receptor signaling within the cytoplasm. In this issue of Immunity, Marek and Kagan (2012) report that Drosophila (d)MyD88 acts instead at the plasma membrane to sort the signaling adaptor Tube.},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Coste Franck, Kemp Cordula, Bobezeau Vanessa, Hetru Charles, Kellenberger Christine, Imler Jean-Luc, Roussel Alain
Crystal structure of Diedel, a marker of the immune response of Drosophila melanogaster Article de journal
Dans: PloS One, vol. 7, no. 3, p. e33416, 2012, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Aphids, Crystallography, imler, Janus Kinases, M3i, Protein Folding, Protein Structure, Signal Transduction, STAT Transcription Factors, Tertiary, Transcription Factors, X-Ray
@article{coste_crystal_2012,
title = {Crystal structure of Diedel, a marker of the immune response of Drosophila melanogaster},
author = {Franck Coste and Cordula Kemp and Vanessa Bobezeau and Charles Hetru and Christine Kellenberger and Jean-Luc Imler and Alain Roussel},
doi = {10.1371/journal.pone.0033416},
issn = {1932-6203},
year = {2012},
date = {2012-01-01},
journal = {PloS One},
volume = {7},
number = {3},
pages = {e33416},
abstract = {BACKGROUND: The Drosophila melanogaster gene CG11501 is up regulated after a septic injury and was proposed to act as a negative regulator of the JAK/STAT signaling pathway. Diedel, the CG11501 gene product, is a small protein of 115 residues with 10 cysteines. METHODOLOGY/PRINCIPAL FINDINGS: We have produced Diedel in Drosophila S2 cells as an extra cellular protein thanks to its own signal peptide and solved its crystal structure at 1.15 Å resolution by SIRAS using an iodo derivative. Diedel is composed of two sub domains SD1 and SD2. SD1 is made of an antiparallel β-sheet covered by an α-helix and displays a ferredoxin-like fold. SD2 reveals a new protein fold made of loops connected by four disulfide bridges. Further structural analysis identified conserved hydrophobic residues on the surface of Diedel that may constitute a potential binding site. The existence of two conformations, cis and trans, for the proline 52 may be of interest as prolyl peptidyl isomerisation has been shown to play a role in several physiological mechanisms. The genome of D. melanogaster contains two other genes coding for proteins homologous to Diedel, namely CG43228 and CG34329. Strikingly, apart from Drosophila and the pea aphid Acyrthosiphon pisum, Diedel-related sequences were exclusively identified in a few insect DNA viruses of the Baculoviridae and Ascoviridae families. CONCLUSION/SIGNIFICANCE: Diedel, a marker of the Drosophila antimicrobial/antiviral response, is a member of a small family of proteins present in drosophilids, aphids and DNA viruses infecting lepidopterans. Diedel is an extracellular protein composed of two sub-domains. Two special structural features (hydrophobic surface patch and cis/trans conformation for proline 52) may indicate a putative interaction site, and support an extra cellular signaling function for Diedel, which is in accordance with its proposed role as negative regulator of the JAK/STAT signaling pathway.},
keywords = {Animals, Aphids, Crystallography, imler, Janus Kinases, M3i, Protein Folding, Protein Structure, Signal Transduction, STAT Transcription Factors, Tertiary, Transcription Factors, X-Ray},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc, Ferrandon Dominique
[Innate immunity crowned 2011 Nobel Prize winner] Article de journal
Dans: Med Sci (Paris), vol. 27, p. 1019–24, 2011, ISSN: 0767-0974 (Print) 0767-0974 (Linking).
Liens | BibTeX | Étiquettes: *Immunity, *Nobel Prize, Biological, ferrandon, Genetic Association Studies, Humans, imler, Immunotherapy/methods/trends, Innate/genetics, M3i, Models, Molecular Targeted Therapy/trends, Seasons, Structure-Activity Relationship, Toll-Like Receptors/chemistry/genetics/isolation & purification/physiology
@article{imler_[innate_2011b,
title = {[Innate immunity crowned 2011 Nobel Prize winner]},
author = {Jean-Luc Imler and Dominique Ferrandon},
url = {http://dx.doi.org.gate1.inist.fr/10.1051/medsci/20112711020},
doi = {10.1051/medsci/20112711020},
issn = {0767-0974 (Print) 0767-0974 (Linking)},
year = {2011},
date = {2011-11-01},
journal = {Med Sci (Paris)},
volume = {27},
pages = {1019--24},
keywords = {*Immunity, *Nobel Prize, Biological, ferrandon, Genetic Association Studies, Humans, imler, Immunotherapy/methods/trends, Innate/genetics, M3i, Models, Molecular Targeted Therapy/trends, Seasons, Structure-Activity Relationship, Toll-Like Receptors/chemistry/genetics/isolation & purification/physiology},
pubstate = {published},
tppubtype = {article}
}
Chtarbanova Stanislava, Imler Jean-Luc
Immunité innée antivirale chez la drosophile Article de journal
Dans: Virologie, vol. 15, no. 5, p. 296-306, 2011, ISSN: 1267-8694.
Résumé | Liens | BibTeX | Étiquettes: *RNA Interference, antiviral immunity, Argonaute, dicer, helicase, imler, M3i, viruses
@article{Chtarbanova2011,
title = {Immunité innée antivirale chez la drosophile},
author = {Stanislava Chtarbanova and Jean-Luc Imler},
url = {http://www.jle.com/fr/revues/vir/e-docs/immunite_innee_antivirale_chez_la_drosophile_290366/article.phtml?tab=texte},
doi = {10.1684/vir.2011.0417},
issn = {1267-8694},
year = {2011},
date = {2011-10-01},
journal = {Virologie},
volume = {15},
number = {5},
pages = {296-306},
abstract = {La drosophile est utilisée depuis une quinzaine d’années comme modèle pour l’étude des mécanismes de l’immunité innée contre les infections bactériennes et fongiques. Les mécanismes de défense de cet insecte contre les infections virales sont maintenant abordés. L’interférence ARN joue un rôle essentiel dans la détection et le contrôle des virus. Ce mécanisme implique la reconnaissance des ARN double brins viraux par Dicer-2 et leur coupure pour former des petits ARN interférants (ARNsi) de 21 nucléotides. Ces ARNsi sont ensuite chargés sur l’enzyme Argonaute-2, qui inhibera spécifiquement les ARN viraux contenant une séquence complémentaire. Une réponse immunitaire inductible contribue également au contrôle des infections virales chez la drosophile. Cette réponse implique les voies de signalisation Toll et IMD, d’une part, (régulant des facteurs de transcription de la famille NF-κB) et J