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2023
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}
}
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.
2022
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}
}
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.
2021
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}
}
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.
Loiseau Vincent, Peccoud Jean, Bouzar Clémence, Guillier Sandra, Fan Jiangbin, Alletti Gianpiero Gueli, Meignin Carine, Herniou Elisabeth A, Federici Brian A, Wennmann Jörg T, Jehle Johannes A, Cordaux Richard, Gilbert Clément
Monitoring Insect Transposable Elements in Large Double-Stranded DNA Viruses Reveals Host-to-Virus and Virus-to-Virus Transposition Article de journal
Dans: Mol Biol Evol, vol. 38, no. 9, p. 3512–3530, 2021, ISSN: 1537-1719.
Résumé | Liens | BibTeX | Étiquettes: M3i, meignin
@article{pmid34191026,
title = {Monitoring Insect Transposable Elements in Large Double-Stranded DNA Viruses Reveals Host-to-Virus and Virus-to-Virus Transposition},
author = {Vincent Loiseau and Jean Peccoud and Clémence Bouzar and Sandra Guillier and Jiangbin Fan and Gianpiero Gueli Alletti and Carine Meignin and Elisabeth A Herniou and Brian A Federici and Jörg T Wennmann and Johannes A Jehle and Richard Cordaux and Clément Gilbert},
doi = {10.1093/molbev/msab198},
issn = {1537-1719},
year = {2021},
date = {2021-08-01},
urldate = {2021-08-01},
journal = {Mol Biol Evol},
volume = {38},
number = {9},
pages = {3512--3530},
abstract = {The mechanisms by which transposable elements (TEs) can be horizontally transferred between animals are unknown, but viruses are possible candidate vectors. Here, we surveyed the presence of host-derived TEs in viral genomes in 35 deep sequencing data sets produced from 11 host-virus systems, encompassing nine arthropod host species (five lepidopterans, two dipterans, and two crustaceans) and six different double-stranded (ds) DNA viruses (four baculoviruses and two iridoviruses). We found evidence of viral-borne TEs in 14 data sets, with frequencies of viral genomes carrying a TE ranging from 0.01% to 26.33% for baculoviruses and from 0.45% to 7.36% for iridoviruses. The analysis of viral populations separated by a single replication cycle revealed that viral-borne TEs originating from an initial host species can be retrieved after viral replication in another host species, sometimes at higher frequencies. Furthermore, we detected a strong increase in the number of integrations in a viral population for a TE absent from the hosts' genomes, indicating that this TE has undergone intense transposition within the viral population. Finally, we provide evidence that many TEs found integrated in viral genomes (15/41) have been horizontally transferred in insects. Altogether, our results indicate that multiple large dsDNA viruses have the capacity to shuttle TEs in insects and they underline the potential of viruses to act as vectors of horizontal transfer of TEs. Furthermore, the finding that TEs can transpose between viral genomes of a viral species sets viruses as possible new niches in which TEs can persist and evolve.},
keywords = {M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
The mechanisms by which transposable elements (TEs) can be horizontally transferred between animals are unknown, but viruses are possible candidate vectors. Here, we surveyed the presence of host-derived TEs in viral genomes in 35 deep sequencing data sets produced from 11 host-virus systems, encompassing nine arthropod host species (five lepidopterans, two dipterans, and two crustaceans) and six different double-stranded (ds) DNA viruses (four baculoviruses and two iridoviruses). We found evidence of viral-borne TEs in 14 data sets, with frequencies of viral genomes carrying a TE ranging from 0.01% to 26.33% for baculoviruses and from 0.45% to 7.36% for iridoviruses. The analysis of viral populations separated by a single replication cycle revealed that viral-borne TEs originating from an initial host species can be retrieved after viral replication in another host species, sometimes at higher frequencies. Furthermore, we detected a strong increase in the number of integrations in a viral population for a TE absent from the hosts' genomes, indicating that this TE has undergone intense transposition within the viral population. Finally, we provide evidence that many TEs found integrated in viral genomes (15/41) have been horizontally transferred in insects. Altogether, our results indicate that multiple large dsDNA viruses have the capacity to shuttle TEs in insects and they underline the potential of viruses to act as vectors of horizontal transfer of TEs. Furthermore, the finding that TEs can transpose between viral genomes of a viral species sets viruses as possible new niches in which TEs can persist and evolve.
2020
Rousseau C, Meignin C
[Viral sensing by RNA helicases] Article de journal
Dans: Virologie (Montrouge), vol. 24, no. 6, p. 419-436, 2020, ISBN: 1267-8694.
Liens | BibTeX | Étiquettes: antiviral innate immunity, M3i, meignin
@article{pmid33441291,
title = {[Viral sensing by RNA helicases]},
author = {C Rousseau and C Meignin},
url = {https://pubmed.ncbi.nlm.nih.gov/33441291/},
doi = {10.1684/vir.2020.0871 },
isbn = {1267-8694},
year = {2020},
date = {2020-12-01},
journal = {Virologie (Montrouge)},
volume = {24},
number = {6},
pages = {419-436},
keywords = {antiviral innate immunity, M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
Rousseau C, Meignin C
Viral sensing by RNA helicases Article de journal
Dans: Virologie (Montrouge), vol. 24, no. 6, p. 36-52, 2020, ISSN: 1267-8694.
Liens | BibTeX | Étiquettes: antiviral innate immunity, M3i, meignin
@article{pmid33441288,
title = {Viral sensing by RNA helicases},
author = {C Rousseau and C Meignin},
url = {https://pubmed.ncbi.nlm.nih.gov/33441288/},
doi = {10.1684/vir.2020.0872},
issn = {1267-8694},
year = {2020},
date = {2020-12-01},
journal = {Virologie (Montrouge)},
volume = {24},
number = {6},
pages = {36-52},
keywords = {antiviral innate immunity, M3i, meignin},
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}
}
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.
Donelick H M, Talide L, Bellet M, Aruscavage P J, Lauret E, Aguiar E R G R, Marques J T, Meignin C, Bass B L
In vitro studies provide insight into effects of Đicer-2 helicase mutations in Đrosophila melanogaster Article de journal
Dans: RNA, vol. 26, no. 12, p. 1847–1861, 2020, ([PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668257PMC7668257] [DOI:hrefhttps://dx.doi.org/10.1261/rna.077289.12010.1261/rna.077289.120] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2136255421362554]).
BibTeX | Étiquettes: antiviral innate immunity, Dicer-2, Drosophila melanogaster, M3i, meignin
@article{pmid32843367,
title = {In vitro studies provide insight into effects of Đicer-2 helicase mutations in Đrosophila melanogaster},
author = {H M Donelick and L Talide and M Bellet and P J Aruscavage and E Lauret and E R G R Aguiar and J T Marques and C Meignin and B L Bass},
year = {2020},
date = {2020-01-01},
journal = {RNA},
volume = {26},
number = {12},
pages = {1847--1861},
note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668257PMC7668257] [DOI:hrefhttps://dx.doi.org/10.1261/rna.077289.12010.1261/rna.077289.120] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2136255421362554]},
keywords = {antiviral innate immunity, Dicer-2, Drosophila melanogaster, M3i, meignin},
pubstate = {published},
tppubtype = {article}
}
Loiseau V, Herniou E A, Moreau Y, Lévêque N, Meignin C, Daeffler L, Federici B, Cordaux R, Gilbert C
Wide spectrum and high frequency of genomic structural variation, including transposable elements, in large double-stranded ĐNA viruses Article de journal
Dans: Virus Evol, vol. 6, no. 1, p. vez060, 2020, ([PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983493PMC6983493] [DOI:hrefhttps://dx.doi.org/10.1093/ve/vez06010.1093/ve/vez060] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2739260627392606]).
BibTeX | Étiquettes: M3i, meignin, virus
@article{pmid32002191,
title = {Wide spectrum and high frequency of genomic structural variation, including transposable elements, in large double-stranded ĐNA viruses},
author = {V Loiseau and E A Herniou and Y Moreau and N Lévêque and C Meignin and L Daeffler and B Federici and R Cordaux and C Gilbert},
year = {2020},
date = {2020-01-01},
journal = {Virus Evol},
volume = {6},
number = {1},
pages = {vez060},
note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983493PMC6983493] [DOI:hrefhttps://dx.doi.org/10.1093/ve/vez06010.1093/ve/vez060] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2739260627392606]},
keywords = {M3i, meignin, virus},
pubstate = {published},
tppubtype = {article}
}
2019
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}
}
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.
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}
}
2018
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}
}
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.
2017
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}
}
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.
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}
}
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.
Gross L, Vicens Q, Einhorn E, Noireterre A, Schaeffer L, Kuhn L, Imler JL, Eriani G, 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 Res, vol. 45, no. 15, p. 8993-9004, 2017, ISBN: 28911115.
Résumé | Liens | BibTeX | Étiquettes: ERIANI, meignin, PPSE, Unité ARN
@article{,
title = {The IRES5'UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure},
author = {L Gross and Q Vicens and E Einhorn and A Noireterre and L Schaeffer and L Kuhn and JL Imler and G Eriani and C Meignin and F Martin},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28911115?dopt=Abstract},
doi = {10.1093/nar/gkx622},
isbn = {28911115},
year = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Nucleic Acids Res},
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 = {ERIANI, meignin, PPSE, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
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.
Gross Lauriane, Vicens Quentin, Einhorn Evelyne, Noireterre Audrey, Schaeffer Laure, Kuhn Lauriane, Imler Jean-Luc, Eriani Gilbert, Meignin Carine, Martin Franck
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, ISSN: 1362-4962.
Résumé | Liens | BibTeX | Étiquettes: meignin, PPSE
@article{gross_ires5utr_2017,
title = {The IRES5'UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure},
author = {Lauriane Gross and Quentin Vicens and Evelyne Einhorn and Audrey Noireterre and Laure Schaeffer and Lauriane Kuhn and Jean-Luc Imler and Gilbert Eriani and Carine Meignin and Franck Martin},
doi = {10.1093/nar/gkx622},
issn = {1362-4962},
year = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
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 = {meignin, PPSE},
pubstate = {published},
tppubtype = {article}
}
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.
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: meignin, PPSE
@article{kuhn_definition_2017b,
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 = {2017-01-01},
urldate = {2017-01-01},
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 = {meignin, PPSE},
pubstate = {published},
tppubtype = {article}
}
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.
2016
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}
}
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}
}
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.
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}
}
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.
2015
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}
}
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.
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}
}
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.
Hafirassou Lamine Mohamed, Meignin Carine, Baumert Thomas, Schuster Catherine
[From fly to man: RACK1, an essential actor of the dependent viral translation of IRES]. Article de journal
Dans: Médecine sciences : M/S, vol. 31, no. 5, p. 469–472, 2015.
@article{hafirassou_[fly_2015b,
title = {[From fly to man: RACK1, an essential actor of the dependent viral translation of IRES].},
author = {Lamine Mohamed Hafirassou and Carine Meignin and Thomas Baumert and Catherine Schuster},
year = {2015},
date = {2015-01-01},
journal = {Médecine sciences : M/S},
volume = {31},
number = {5},
pages = {469--472},
keywords = {meignin},
pubstate = {published},
tppubtype = {article}
}
Girardi E, Lefèvre M, Chane-Woon-Ming B, Paro S, Claydon B, Imler JL, Meignin C, Pfeffer S
Cross-species comparative analysis of Dicer proteins during Sindbis virus infection. Article de journal
Dans: Sci Rep, vol. 5, p. 10693, 2015, ISBN: 26024431.
Résumé | Liens | BibTeX | Étiquettes: meignin, PFEFFER, Unité ARN
@article{,
title = {Cross-species comparative analysis of Dicer proteins during Sindbis virus infection.},
author = {E Girardi and M Lefèvre and B Chane-Woon-Ming and S Paro and B Claydon and JL Imler and C Meignin and S Pfeffer},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26024431?dopt=Abstract},
doi = {10.1038/srep10693},
isbn = {26024431},
year = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {Sci Rep},
volume = {5},
pages = {10693},
abstract = {In plants and invertebrates RNA silencing is a major defense mechanism against virus infections. The first event in RNA silencing is dicing of long double stranded RNAs into small interfering RNAs (siRNAs). The Dicer proteins involved in this process are phylogenetically conserved and have the same domain organization. Accordingly, the production of viral derived siRNAs has also been observed in the mouse, but only in restricted cell types. To gain insight on this restriction, we compare the dicing activity of human Dicer and fly Dicer-2 in the context of Sindbis virus (SINV) infection. Expression of human Dicer in flies inefficiently rescues the production of viral siRNAs but confers some protection against SINV. Conversely, expression of Dicer-2 in human cells allows the production of viral 21 nt small RNAs. However, this does not confer resistance to viral infection, but on the contrary results in stronger accumulation of viral RNA. We further show that Dicer-2 expression in human cells perturbs interferon (IFN) signaling pathways and antagonizes protein kinase R (PKR)-mediated antiviral immunity. Overall, our data suggest that a functional incompatibility between the Dicer and IFN pathways explains the predominance of the IFN response in mammalian somatic cells.},
keywords = {meignin, PFEFFER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
In plants and invertebrates RNA silencing is a major defense mechanism against virus infections. The first event in RNA silencing is dicing of long double stranded RNAs into small interfering RNAs (siRNAs). The Dicer proteins involved in this process are phylogenetically conserved and have the same domain organization. Accordingly, the production of viral derived siRNAs has also been observed in the mouse, but only in restricted cell types. To gain insight on this restriction, we compare the dicing activity of human Dicer and fly Dicer-2 in the context of Sindbis virus (SINV) infection. Expression of human Dicer in flies inefficiently rescues the production of viral siRNAs but confers some protection against SINV. Conversely, expression of Dicer-2 in human cells allows the production of viral 21 nt small RNAs. However, this does not confer resistance to viral infection, but on the contrary results in stronger accumulation of viral RNA. We further show that Dicer-2 expression in human cells perturbs interferon (IFN) signaling pathways and antagonizes protein kinase R (PKR)-mediated antiviral immunity. Overall, our data suggest that a functional incompatibility between the Dicer and IFN pathways explains the predominance of the IFN response in mammalian somatic cells.
2014
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}
}
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.
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}
}
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.
2012
Zhang Fan, Wang Jie, Xu Jia, Zhang Zhao, Koppetsch Birgit S, Schultz Nadine, Vreven Thom, Meignin Carine, Davis Ilan, Zamore Phillip D, Weng Zhiping, Theurkauf William E
UAP56 Couples piRNA Clusters to the Perinuclear Transposon Silencing Machinery. Article de journal
Dans: Cell, vol. 151, no. 4, p. 871–884, 2012.
@article{zhang_uap56_2012,
title = {UAP56 Couples piRNA Clusters to the Perinuclear Transposon Silencing Machinery.},
author = {Fan Zhang and Jie Wang and Jia Xu and Zhao Zhang and Birgit S Koppetsch and Nadine Schultz and Thom Vreven and Carine Meignin and Ilan Davis and Phillip D Zamore and Zhiping Weng and William E Theurkauf},
year = {2012},
date = {2012-01-01},
journal = {Cell},
volume = {151},
number = {4},
pages = {871--884},
keywords = {meignin},
pubstate = {published},
tppubtype = {article}
}
