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I2CT
Immunologie, Immunopathologie et Chimie Thérapeutique
Publications
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
Franchet Adrien, Niehus Sebastian, Caravello Gaetan, Ferrandon Dominique
Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies Article de journal
Dans: Nature Microbiology, vol. 4, no. 4, p. 645, 2019, ISBN: 2058-5276.
Résumé | Liens | BibTeX | Étiquettes: Drosophila, ferrandon, Host-Parasite Interactions, Lipids, M3i, metabolism, microsporidia
@article{Franchet2019,
title = {Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies},
author = {Adrien Franchet and Sebastian Niehus and Gaetan Caravello and Dominique Ferrandon},
editor = {Nature Publishing Group},
url = {https://www.nature.com/articles/s41564-018-0344-y},
doi = {10.1038/s41564-018-0344-y},
isbn = {2058-5276},
year = {2019},
date = {2019-01-28},
journal = {Nature Microbiology},
volume = {4},
number = {4},
pages = {645},
abstract = {A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation.},
keywords = {Drosophila, ferrandon, Host-Parasite Interactions, Lipids, M3i, metabolism, microsporidia},
pubstate = {published},
tppubtype = {article}
}
A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation.
Achee Nicole L., Grieco John P., Vatandoost Hassan, Seixas Gonçalo, Pinto Joao, Ching-NG Lee, Martins Ademir J., Juntarajumnong Waraporn, Corbel Vincent, Gouagna Clement, David Jean-Philippe, Logan James G., Orsborne James, Marois Eric, Devine Gregor J., Vontas John
Alternative strategies for mosquito-borne arbovirus control Article de journal
Dans: PLoS Neglected Tropical Diseases, 2019.
Résumé | Liens | BibTeX | Étiquettes: arbovirus, M3i, marois, mosquito
@article{Achee2019,
title = {Alternative strategies for mosquito-borne arbovirus control},
author = { Nicole L. Achee and John P. Grieco and Hassan Vatandoost and Gonçalo Seixas and Joao Pinto and Lee Ching-NG and Ademir J. Martins and Waraporn Juntarajumnong and Vincent Corbel and Clement Gouagna and Jean-Philippe David and James G. Logan and James Orsborne and Eric Marois and Gregor J. Devine and John Vontas
},
url = {https://doi.org/10.1371/journal.pntd.0006822},
doi = {10.1371/journal.pntd.0006822},
year = {2019},
date = {2019-01-03},
journal = {PLoS Neglected Tropical Diseases},
abstract = {International public health workers are challenged by the burden of arthropod-borne viral diseases, to include mosquito-borne arboviruses transmitted by Aedes aegypti and A. albopictus due in part to lack of sustainable vector control and insecticide resistance (IR), as well as the inability to scale up and sustain existing interventions for prevention of urban epidemics. As a consequence, there has been increasing interest to advance the development of alternative methods. This review provides a general overview of alternative vector-control strategies under development for the control of arbovirus mosquito vectors and highlights how each could offer innovative public health value. Considerations to regulations, acceptance, and sustainability are also provided.},
keywords = {arbovirus, M3i, marois, mosquito},
pubstate = {published},
tppubtype = {article}
}
International public health workers are challenged by the burden of arthropod-borne viral diseases, to include mosquito-borne arboviruses transmitted by Aedes aegypti and A. albopictus due in part to lack of sustainable vector control and insecticide resistance (IR), as well as the inability to scale up and sustain existing interventions for prevention of urban epidemics. As a consequence, there has been increasing interest to advance the development of alternative methods. This review provides a general overview of alternative vector-control strategies under development for the control of arbovirus mosquito vectors and highlights how each could offer innovative public health value. Considerations to regulations, acceptance, and sustainability are also provided.
2018
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}
}
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.
Gros Frédéric, Fournel Sylvie, Liégeois Samuel, Richard Daniel, Soulas-Sprauel Pauline
Atlas d'immunologie Ouvrage
Editions Dunod, 2018, ISBN: 9782100767052.
Résumé | BibTeX | Étiquettes: atlas, cours, ferrandon, immunologie, M3i
@book{Gros2018,
title = {Atlas d'immunologie},
author = {Frédéric Gros and Sylvie Fournel and Samuel Liégeois and Daniel Richard and Pauline Soulas-Sprauel},
editor = {Editions Dunod },
isbn = {9782100767052},
year = {2018},
date = {2018-09-01},
edition = {Editions Dunod},
abstract = {Cet ouvrage présente de façon synthétique et illustrée, les nombreux mécanismes de la réponse immunitaire et les différents types de cellules intervenant dans le système immunitaire.
Les notions de base en immunologie, les modes d'explorations de l'immunité et les applications médicales de l'immunologie et les pathologies sont présentés sous forme de fiches illustrées par de nombreux schémas et photos en couleur.},
keywords = {atlas, cours, ferrandon, immunologie, M3i},
pubstate = {published},
tppubtype = {book}
}
Cet ouvrage présente de façon synthétique et illustrée, les nombreux mécanismes de la réponse immunitaire et les différents types de cellules intervenant dans le système immunitaire.
Les notions de base en immunologie, les modes d'explorations de l'immunité et les applications médicales de l'immunologie et les pathologies sont présentés sous forme de fiches illustrées par de nombreux schémas et photos en couleur.
Les notions de base en immunologie, les modes d'explorations de l'immunité et les applications médicales de l'immunologie et les pathologies sont présentés sous forme de fiches illustrées par de nombreux schémas et photos en couleur.
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.
J. Bouyer, E. Marois
Pests and vector-borne diseases in the livestock industry Chapitre d'ouvrage
Dans: Academic, Wageningen (Ed.): vol. 5, Chapitre Genetic control of vectors, p. 435–451, 2018, ISBN: 9789086868636 .
Résumé | Liens | BibTeX | Étiquettes: insect resistance, M3i, marois
@inbook{Bouyer2018,
title = {Pests and vector-borne diseases in the livestock industry},
author = {Bouyer J. and Marois E.},
editor = {Wageningen Academic},
url = {https://doi.org/10.3920/978-90-8686-863-6_14 },
doi = {10.3920/978-90-8686-863-6_14},
isbn = {9789086868636 },
year = {2018},
date = {2018-08-15},
volume = {5},
pages = {435–451},
chapter = {Genetic control of vectors},
series = {Ecology and Control of Vector-borne Diseases},
abstract = {In a context of tighter regulations on approved insecticide molecules, the spread of insecticide resistance in insect vectors of human and animal diseases and the introduction of exotic vectors to new territories call for the development of new pest control methods and strategies. New genetic control methods, related to the ancestral sterile insect technique (SIT), show particular promise and are being developed in response to increasing health and agricultural challenges. These include the use of symbionts like Wolbachia and the use of transgenic insect strains, some of which incorporate gene editing techniques that can lead to transgene spread (gene drive). Here we present the principles, associated opportunities and risks, as well as the degree of advancement of these various techniques for a subset of livestock pests and disease vectors including screwworms, tsetse, mosquitoes and stomoxes. We then present some case studies on recent improvements in the use of the SIT in tsetse and the release of insects carrying a dominant lethal gene, symbiont-based approaches and gene drive in mosquitoes. Finally, we call to speed up the development of genetic control, within a rigorous benefit-risk analysis framework including international public consultation.},
keywords = {insect resistance, M3i, marois},
pubstate = {published},
tppubtype = {inbook}
}
In a context of tighter regulations on approved insecticide molecules, the spread of insecticide resistance in insect vectors of human and animal diseases and the introduction of exotic vectors to new territories call for the development of new pest control methods and strategies. New genetic control methods, related to the ancestral sterile insect technique (SIT), show particular promise and are being developed in response to increasing health and agricultural challenges. These include the use of symbionts like Wolbachia and the use of transgenic insect strains, some of which incorporate gene editing techniques that can lead to transgene spread (gene drive). Here we present the principles, associated opportunities and risks, as well as the degree of advancement of these various techniques for a subset of livestock pests and disease vectors including screwworms, tsetse, mosquitoes and stomoxes. We then present some case studies on recent improvements in the use of the SIT in tsetse and the release of insects carrying a dominant lethal gene, symbiont-based approaches and gene drive in mosquitoes. Finally, we call to speed up the development of genetic control, within a rigorous benefit-risk analysis framework including international public consultation.
Haller Samantha, Franchet Adrien, Hakkim A, Chen J, Drenkard E, Yu S, Schirmeier Steffi, Li Zi, Martins Nelson, Ausubel FM, Liégeois Samuel, Ferrandon Dominique
Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization Article de journal
Dans: EMBO Reports, 2018.
Liens | BibTeX | Étiquettes: Drosophila, ferrandon, M3i, Opsonin Proteins, Phagocytosis, Pseudomonas aeruginosa, Quorum Sensing
@article{S2018,
title = {Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization},
author = {Samantha Haller and Adrien Franchet and A Hakkim and J Chen and E Drenkard and S Yu and Steffi Schirmeier and Zi Li and Nelson Martins and FM Ausubel and Samuel Liégeois and Dominique Ferrandon},
url = {http://embor.embopress.org/content/early/2018/03/09/embr.201744880},
doi = {10.15252/embr.201744880},
year = {2018},
date = {2018-03-09},
journal = {EMBO Reports},
keywords = {Drosophila, ferrandon, M3i, Opsonin Proteins, Phagocytosis, Pseudomonas aeruginosa, Quorum Sensing},
pubstate = {published},
tppubtype = {article}
}
Dong Yuemei, Simões Maria L., Marois Eric, Dimopoulos George
CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection Article de journal
Dans: PLoS Pathog, vol. 14, no. 3, 2018.
Résumé | Liens | BibTeX | Étiquettes: Anopheles gambiae, CRISPR/Cas9, Knockout, M3i, Malaria, marois
@article{Dong2018,
title = {CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection},
author = { Yuemei Dong and Maria L. Simões and Eric Marois and George Dimopoulos },
url = {https://doi.org/10.1371/journal.ppat.1006898},
doi = {10.1371/journal.ppat.1006898},
year = {2018},
date = {2018-03-08},
urldate = {2018-03-08},
journal = {PLoS Pathog},
volume = {14},
number = {3},
abstract = {Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito’s susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants developed into adult mosquitoes that showed profound suppression of infection with both human and rodent malaria parasites at the oocyst and sporozoite stages. FREP1 inactivation, however, resulted in fitness costs including a significantly lower blood-feeding propensity, fecundity and egg hatching rate, a retarded pupation time, and reduced longevity after a blood meal.},
keywords = {Anopheles gambiae, CRISPR/Cas9, Knockout, M3i, Malaria, marois},
pubstate = {published},
tppubtype = {article}
}
Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito’s susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants developed into adult mosquitoes that showed profound suppression of infection with both human and rodent malaria parasites at the oocyst and sporozoite stages. FREP1 inactivation, however, resulted in fitness costs including a significantly lower blood-feeding propensity, fecundity and egg hatching rate, a retarded pupation time, and reduced longevity after a blood meal.
Issa Najwa, Guillaumot Nina, Lauret Emilie, Matt Nicolas, Scaeffer-Reiss Christine, Dorsselaer Alain Van, Reichhart Jean-Marc, Veillard Florian
The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway. Article de journal
Dans: Molecular Cell, vol. 69, no. 4, p. 539-550, 2018, ISSN: 1097-2765.
Résumé | Liens | BibTeX | Étiquettes: circulating protease, immune sensor, M3i, matt, persephone, Protease, proteolitic activities, reichhart, toll pathway
@article{Issa2018,
title = {The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway.},
author = {Najwa Issa and Nina Guillaumot and Emilie Lauret and Nicolas Matt and Christine Scaeffer-Reiss and Alain Van Dorsselaer and Jean-Marc Reichhart and Florian Veillard},
url = {http://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30058-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276518300583%3Fshowall%3Dtrue},
doi = {10.1016/j.molcel.2018.01.029},
issn = {1097-2765},
year = {2018},
date = {2018-02-15},
journal = {Molecular Cell},
volume = {69},
number = {4},
pages = {539-550},
abstract = {Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.},
keywords = {circulating protease, immune sensor, M3i, matt, persephone, Protease, proteolitic activities, reichhart, toll pathway},
pubstate = {published},
tppubtype = {article}
}
Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.
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}
}
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.
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.
G Triller, SW Scally, G Costa, M Pissarev, C Kreschel, A Bosch, E Marois, BK Sack, R Murugan, AM Salman, CJ Janse, SM Khan, SH Kappe, AA Adegnika, B Mordmüller, EA Levashina, JP Julien, H Wardemann
Natural parasite exposure induces protective human anti-malarial antibodies Article de journal
Dans: Immunity , vol. 47, iss. 6, p. 1197-1209, 2017.
Résumé | Liens | BibTeX | Étiquettes: anti-malarial antibodie, M3i, marois
@article{Triller2017,
title = {Natural parasite exposure induces protective human anti-malarial antibodies},
author = {Triller G and Scally SW and Costa G and Pissarev M and Kreschel C and Bosch A and Marois E and Sack BK and Murugan R and Salman AM and Janse CJ and Khan SM and Kappe SH and Adegnika AA and Mordmüller B and Levashina EA and Julien JP and Wardemann H},
url = {https://doi.org/10.1016/j.immuni.2017.11.007},
doi = {10.1016/j.immuni.2017.11.007},
year = {2017},
date = {2017-12-19},
journal = {Immunity },
volume = {47},
issue = {6},
pages = {1197-1209},
abstract = {Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but protective humoral immunity is difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines. },
keywords = {anti-malarial antibodie, M3i, marois},
pubstate = {published},
tppubtype = {article}
}
Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but protective humoral immunity is difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines.
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.
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}
}
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.
Volohonsky Gloria, Hopp Ann-Katrin, Saenger Mélanie, Soichot Julien, Scholze Heidi, Boch Jens, Blandin Stéphanie A, Marois Eric
Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae Article de journal
Dans: PLOS Pathogens, vol. 13, no. 1, p. e1006113, 2017, ISSN: 1553-7374.
Liens | BibTeX | Étiquettes: Anopheles gambiae, anti-parasitic factor, blandin, M3i, Malaria, marois, TEP1, transgenic
@article{volohonsky_transgenic_2017,
title = {Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae},
author = {Gloria Volohonsky and Ann-Katrin Hopp and Mélanie Saenger and Julien Soichot and Heidi Scholze and Jens Boch and Stéphanie A Blandin and Eric Marois},
editor = {Kenneth D Vernick},
url = {http://dx.plos.org/10.1371/journal.ppat.1006113},
doi = {10.1371/journal.ppat.1006113},
issn = {1553-7374},
year = {2017},
date = {2017-01-01},
urldate = {2017-02-01},
journal = {PLOS Pathogens},
volume = {13},
number = {1},
pages = {e1006113},
keywords = {Anopheles gambiae, anti-parasitic factor, blandin, M3i, Malaria, marois, TEP1, transgenic},
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}
}
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.
Koltun Bella, Shackelford Eliza, Bonnay François, Matt Nicolas, Reichhart Jean-Marc, Orian Amir
The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity Article de journal
Dans: The International Journal of Developmental Biology, vol. 61, no. 3-4-5, p. 319–327, 2017, ISSN: 0214-6282.
Liens | BibTeX | Étiquettes: Dgrn, Drosophila, innate immunity, Ligase, M3i, matt, reichhart, SUMO, target, ubiquitin
@article{koltun_sumo-targeted_2017,
title = {The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity},
author = {Bella Koltun and Eliza Shackelford and François Bonnay and Nicolas Matt and Jean-Marc Reichhart and Amir Orian},
url = {http://www.intjdevbiol.com/paper.php?doi=160250ao},
doi = {10.1387/ijdb.160250ao},
issn = {0214-6282},
year = {2017},
date = {2017-01-01},
urldate = {2017-07-12},
journal = {The International Journal of Developmental Biology},
volume = {61},
number = {3-4-5},
pages = {319--327},
keywords = {Dgrn, Drosophila, innate immunity, Ligase, M3i, matt, reichhart, SUMO, target, ubiquitin},
pubstate = {published},
tppubtype = {article}
}
Chamy Laure El, Matt Nicolas, Reichhart Jean-Marc
Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster Article de journal
Dans: Microbiology Spectrum, vol. 5, no. 1, 2017, ISSN: 2165-0497.
Liens | BibTeX | Étiquettes: Drosophila melanogaster, M3i, matt, Myeloid-Like Cell Origins, reichhart
@article{Chamy2017,
title = {Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster},
author = {Laure El Chamy and Nicolas Matt and Jean-Marc Reichhart},
url = {http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0038-2016},
doi = {10.1128/microbiolspec.MCHD-0038-2016},
issn = {2165-0497},
year = {2017},
date = {2017-01-01},
urldate = {2017-07-12},
journal = {Microbiology Spectrum},
volume = {5},
number = {1},
keywords = {Drosophila melanogaster, M3i, matt, Myeloid-Like Cell Origins, reichhart},
pubstate = {published},
tppubtype = {article}
}
2016
Lee Kwang-Zin, Lestradet Matthieu, Socha Catherine, Schirmeier Stefanie, Schmitz Antonin, Spenlé Caroline, Lefebvre Olivier, Keime Céline, Yamba Wennida M., Bou Aoun Richard, Liegeois Samuel, Schwab Yannick, Simon-Assmann Patricia, Dalle Frédéric, Ferrandon Dominique
Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack Article de journal
Dans: Cell Host & Microbe, 2016, ISSN: 1931-3128.
Résumé | Liens | BibTeX | Étiquettes: Epithelium, ferrandon, gut, M3i, resilience
@article{Lee2016,
title = {Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack},
author = {Kwang-Zin Lee and Matthieu Lestradet and Catherine Socha and Stefanie Schirmeier and Antonin Schmitz and Caroline Spenlé and Olivier Lefebvre and Céline Keime and Wennida M. Yamba and Richard Bou Aoun and Samuel Liegeois and Yannick Schwab and Patricia Simon-Assmann and Frédéric Dalle and Dominique Ferrandon},
editor = {L Abate},
url = {http://www.sciencedirect.com/science/article/pii/S193131281630436X},
doi = {10.1016/j.chom.2016.10.010},
issn = {1931-3128},
year = {2016},
date = {2016-11-23},
urldate = {2016-11-25},
journal = {Cell Host & Microbe},
abstract = {Summary
Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.},
keywords = {Epithelium, ferrandon, gut, M3i, resilience},
pubstate = {published},
tppubtype = {article}
}
Summary
Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.
Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.
Ehrhardt Katharina, Deregnaucourt Christiane, Goetz Alice-Anne, Tzanova Tzvetomira, Gallo Valentina, Arese Paolo, Pradines Bruno, Adjalley Sophie H, Bagrel Denyse, Blandin Stephanie A, Lanzer Michael, Davioud-Charvet Elisabeth
The redox-cycler plasmodione is a fast acting antimalarial lead compound with pronounced activity against sexual and early asexual blood-stage parasites Article de journal
Dans: Antimicrob. Agents Chemother., vol. 60, no. 9, p. 5146-5158, 2016, ISSN: 1098-6596.
Résumé | Liens | BibTeX | Étiquettes: antimalarial, blandin, M3i, parasites, Plasmodium, redox-cycler
@article{ehrhardt_redox-cycler_2016,
title = {The redox-cycler plasmodione is a fast acting antimalarial lead compound with pronounced activity against sexual and early asexual blood-stage parasites},
author = {Katharina Ehrhardt and Christiane Deregnaucourt and Alice-Anne Goetz and Tzvetomira Tzanova and Valentina Gallo and Paolo Arese and Bruno Pradines and Sophie H Adjalley and Denyse Bagrel and Stephanie A Blandin and Michael Lanzer and Elisabeth Davioud-Charvet},
url = {http://aac.asm.org/content/60/9/5146},
doi = {10.1128/AAC.02975-15},
issn = {1098-6596},
year = {2016},
date = {2016-09-01},
journal = {Antimicrob. Agents Chemother.},
volume = {60},
number = {9},
pages = {5146-5158},
abstract = {Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox-cyclers - a strategy that is broadly recognized for the development of new antimalarial agents. Here, we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intra-erythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common resistance mechanisms to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a fast killing speed as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that it is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents.},
keywords = {antimalarial, blandin, M3i, parasites, Plasmodium, redox-cycler},
pubstate = {published},
tppubtype = {article}
}
Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox-cyclers - a strategy that is broadly recognized for the development of new antimalarial agents. Here, we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intra-erythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common resistance mechanisms to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a fast killing speed as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that it is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents.
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}
}
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.
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}
}
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.
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.
Baron Olga Lucia, Deleury Emeline, Reichhart Jean-Marc, Coustau Christine
The LBP/BPI multigenic family in invertebrates: Evolutionary history and evidences of specialization in mollusks Article de journal
Dans: Developmental & Comparative Immunology, vol. 57, p. 20–30, 2016, ISSN: 0145305X.
Liens | BibTeX | Étiquettes: BPI, Evolution, Invertebrate, LBP, M3i, mollusks, multigenic family, reichhart
@article{baron_lbp/bpi_2016,
title = {The LBP/BPI multigenic family in invertebrates: Evolutionary history and evidences of specialization in mollusks},
author = {Olga Lucia Baron and Emeline Deleury and Jean-Marc Reichhart and Christine Coustau},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0145305X15300756},
doi = {10.1016/j.dci.2015.11.006},
issn = {0145305X},
year = {2016},
date = {2016-01-01},
urldate = {2017-07-12},
journal = {Developmental & Comparative Immunology},
volume = {57},
pages = {20--30},
keywords = {BPI, Evolution, Invertebrate, LBP, M3i, mollusks, multigenic family, reichhart},
pubstate = {published},
tppubtype = {article}
}
Enkler L, Richer D, Marchand A L, Ferrandon D, Jossinet F
Genome engineering in the yeast pathogen Candida glabrata using the CRISPR-Cas9 system. Article de journal
Dans: Sci Rep, vol. 6, p. 35766, 2016, ISBN: 27767081.
Résumé | Liens | BibTeX | Étiquettes: JOSSINET, M3i, Unité ARN
@article{,
title = {Genome engineering in the yeast pathogen Candida glabrata using the CRISPR-Cas9 system.},
author = {L Enkler and D Richer and A L Marchand and D Ferrandon and F Jossinet},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27767081?dopt=Abstract},
doi = {10.1038/srep35766},
isbn = {27767081},
year = {2016},
date = {2016-01-01},
journal = {Sci Rep},
volume = {6},
pages = {35766},
abstract = {Among Candida species, the opportunistic fungal pathogen Candida glabrata has become the second most common causative agent of candidiasis in the world and a major public health concern. Yet, few molecular tools and resources are available to explore the biology of C. glabrata and to better understand its virulence during infection. In this study, we describe a robust experimental strategy to generate loss-of-function mutants in C. glabrata. The procedure is based on the development of three main tools: (i) a recombinant strain of C. glabrata constitutively expressing the CRISPR-Cas9 system, (ii) an online program facilitating the selection of the most efficient guide RNAs for a given C. glabrata gene, and (iii) the identification of mutant strains by the Surveyor technique and sequencing. As a proof-of-concept, we have tested the virulence of some mutants in vivo in a Drosophila melanogaster infection model. Our results suggest that yps11 and a previously uncharacterized serine/threonine kinase are involved, directly or indirectly, in the ability of the pathogenic yeast to infect this model host organism.},
keywords = {JOSSINET, M3i, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Among Candida species, the opportunistic fungal pathogen Candida glabrata has become the second most common causative agent of candidiasis in the world and a major public health concern. Yet, few molecular tools and resources are available to explore the biology of C. glabrata and to better understand its virulence during infection. In this study, we describe a robust experimental strategy to generate loss-of-function mutants in C. glabrata. The procedure is based on the development of three main tools: (i) a recombinant strain of C. glabrata constitutively expressing the CRISPR-Cas9 system, (ii) an online program facilitating the selection of the most efficient guide RNAs for a given C. glabrata gene, and (iii) the identification of mutant strains by the Surveyor technique and sequencing. As a proof-of-concept, we have tested the virulence of some mutants in vivo in a Drosophila melanogaster infection model. Our results suggest that yps11 and a previously uncharacterized serine/threonine kinase are involved, directly or indirectly, in the ability of the pathogenic yeast to infect this model host organism.
2015
Veillard Florian, Troxler Laurent, Reichhart Jean-Marc
Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation Article de journal
Dans: Biochimie, vol. 122, p. 255-269, 2015, ISBN: 0300-9084.
Résumé | Liens | BibTeX | Étiquettes: bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll
@article{veillard_drosophila_2015,
title = {Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation},
author = {Florian Veillard and Laurent Troxler and Jean-Marc Reichhart},
url = {http://www.sciencedirect.com/science/article/pii/S030090841500317X},
doi = {10.1016/j.biochi.2015.10.007},
isbn = {0300-9084},
year = {2015},
date = {2015-10-08},
journal = {Biochimie},
volume = {122},
pages = {255-269},
abstract = {Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors.},
keywords = {bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll},
pubstate = {published},
tppubtype = {article}
}
Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors.
Chamy Laure El, Matt Nicolas, Ntwasa Monde, Reichhart Jean-Marc
The multilayered innate immune defense of the gut Article de journal
Dans: Biomed J, vol. 38, no. 4, p. 276–284, 2015, ISSN: 2320-2890.
Résumé | Liens | BibTeX | Étiquettes: fly, gut, innate immunity, M3i, matt, reichhart
@article{el_chamy_multilayered_2015,
title = {The multilayered innate immune defense of the gut},
author = {Laure El Chamy and Nicolas Matt and Monde Ntwasa and Jean-Marc Reichhart},
url = {http://www.biomedj.org/text.asp?2015/38/4/276/158621},
doi = {10.4103/2319-4170.158621},
issn = {2320-2890},
year = {2015},
date = {2015-08-01},
journal = {Biomed J},
volume = {38},
number = {4},
pages = {276--284},
abstract = {In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.},
keywords = {fly, gut, innate immunity, M3i, matt, reichhart},
pubstate = {published},
tppubtype = {article}
}
In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.
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.
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}
}
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.
Volohonsky Gloria, Terenzi Olivier, Soichot Julien, Naujoks Daniel A, Nolan Tony, Windbichler Nikolai, Kapps Delphine, Smidler Andie L, Vittu Anaïs, Costa Giulia, Steinert Stefanie, Levashina Elena A, Blandin Stéphanie A, Marois Eric
Tools for Anopheles gambiae Transgenesis Article de journal
Dans: G3 (Bethesda), vol. 5, no. 6, p. 1151-63, 2015.
Résumé | Liens | BibTeX | Étiquettes: Anopheles gambiae, bioinformatic, blandin, M3i, marois, transgenesis
@article{G2015,
title = {Tools for Anopheles gambiae Transgenesis},
author = {Gloria Volohonsky and Olivier Terenzi and Julien Soichot and Daniel A Naujoks and Tony Nolan and Nikolai Windbichler and Delphine Kapps and Andie L Smidler and Anaïs Vittu and Giulia Costa and Stefanie Steinert and Elena A Levashina and Stéphanie A Blandin and Eric Marois},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25869647},
year = {2015},
date = {2015-04-13},
journal = {G3 (Bethesda)},
volume = {5},
number = {6},
pages = {1151-63},
abstract = {Transgenesis is an essential tool to investigate gene function and to introduce desired characters in laboratory organisms. Setting-up transgenesis in non-model organisms is challenging due to the diversity of biological life traits and due to knowledge gaps in genomic information. Some procedures will be broadly applicable to many organisms, and others have to be specifically developed for the target species. Transgenesis in disease vector mosquitoes has existed since the 2000s but has remained limited by the delicate biology of these insects. Here, we report a compilation of the transgenesis tools that we have designed for the malaria vector Anopheles gambiae, including new docking strains, convenient transgenesis plasmids, a puromycin resistance selection marker, mosquitoes expressing cre recombinase, and various reporter lines defining the activity of cloned promoters. This toolbox contributed to rendering transgenesis routine in this species and is now enabling the development of increasingly refined genetic manipulations such as targeted mutagenesis. Some of the reagents and procedures reported here are easily transferable to other nonmodel species, including other disease vector or agricultural pest insects.},
keywords = {Anopheles gambiae, bioinformatic, blandin, M3i, marois, transgenesis},
pubstate = {published},
tppubtype = {article}
}
Transgenesis is an essential tool to investigate gene function and to introduce desired characters in laboratory organisms. Setting-up transgenesis in non-model organisms is challenging due to the diversity of biological life traits and due to knowledge gaps in genomic information. Some procedures will be broadly applicable to many organisms, and others have to be specifically developed for the target species. Transgenesis in disease vector mosquitoes has existed since the 2000s but has remained limited by the delicate biology of these insects. Here, we report a compilation of the transgenesis tools that we have designed for the malaria vector Anopheles gambiae, including new docking strains, convenient transgenesis plasmids, a puromycin resistance selection marker, mosquitoes expressing cre recombinase, and various reporter lines defining the activity of cloned promoters. This toolbox contributed to rendering transgenesis routine in this species and is now enabling the development of increasingly refined genetic manipulations such as targeted mutagenesis. Some of the reagents and procedures reported here are easily transferable to other nonmodel species, including other disease vector or agricultural pest 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.
Neafsey D E, Waterhouse R M, Abai M R, Aganezov S S, Alekseyev M A, Allen J E, Amon J, Arcà B, Arensburger P, Artemov G, Assour L A, Basseri H, Berlin A, Birren B W, Blandin Stéphanie A, Brockman A I, Burkot T R, Burt A, Chan C S, Chauve C, Chiu J C, Christensen M, Costantini C, Davidson V L M, Deligianni E, Dottorini T, Dritsou V, Gabriel S B, Guelbeogo W M, Hall A B, Han M W, Hlaing T, Hughes D S T, Jenkins A M, Jiang X, Jungreis I, Kakani E G, Kamali M, Kemppainen P, Kennedy R C, Kirmitzoglou I K, Koekemoer L L, Laban N, Langridge N, Lawniczak M K N, Lirakis M, Lobo N F, Lowy E, MacCallum R M, Mao C, Maslen G, Mbogo C, McCarthy J, Michel K, Mitchell S N, Moore W, Murphy K A, Naumenko A N, Nolan Tony, Novoa E M, O’Loughlin S, Oringanje C, Oshaghi M A, Pakpour N, Papathanos P A, Peery A N, Povelones Michael, Prakash A, Price D A, Rajaraman A, Reimer L J, Rinker D C, Rokas A, Russell T L, Sagnon N F, Sharakhova M V, Shea T, Simão F A, Simard F, Slotman M A, Somboon P, Stegniy V, Struchiner C J, Thomas G W C, Tojo M, Topalis P, Tubio J M C, Unger M F, Vontas J, Walton C, Wilding C S, Willis J H, Wu Y-C, Yan G, Zdobnov E M, Zhou X, Catteruccia Flaminia, Christophides Georges K, Collins F H, Cornman R S, Crisanti Andrea, Donnelly M J, Emrich S J, Fontaine M C, Gelbart W, Hahn M W, Hansen I A, Howell P I, Kafatos Fotis C, Kellis M, Lawson D, Louis C, Luckhart S, Muskavitch M A T, Ribeiro J M, Riehle M A, Sharakhov I V, Tu Z, Zwiebel L J, Besansky N J
Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes. Article de journal
Dans: Science, vol. 347, no. 6217, p. 1258522, 2015.
Résumé | Liens | BibTeX | Étiquettes: Anopheles, blandin, genomes, M3i
@article{DE2015,
title = {Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes.},
author = {D E Neafsey and R M Waterhouse and M R Abai and S S Aganezov and M A Alekseyev and J E Allen and J Amon and B Arcà and P Arensburger and G Artemov and L A Assour and H Basseri and A Berlin and B W Birren and Stéphanie A Blandin and A I Brockman and T R Burkot and A Burt and C S Chan and C Chauve and J C Chiu and M Christensen and C Costantini and V L M Davidson and E Deligianni and T Dottorini and V Dritsou and S B Gabriel and W M Guelbeogo and A B Hall and M W Han and T Hlaing and D S T Hughes and A M Jenkins and X Jiang and I Jungreis and E G Kakani and M Kamali and P Kemppainen and R C Kennedy and I K Kirmitzoglou and L L Koekemoer and N Laban and N Langridge and M K N Lawniczak and M Lirakis and N F Lobo and E Lowy and R M MacCallum and C Mao and G Maslen and C Mbogo and J McCarthy and K Michel and S N Mitchell and W Moore and K A Murphy and A N Naumenko and Tony Nolan and E M Novoa and S O’Loughlin and C Oringanje and M A Oshaghi and N Pakpour and P A Papathanos and A N Peery and Michael Povelones and A Prakash and D A Price and A Rajaraman and L J Reimer and D C Rinker and A Rokas and T L Russell and N F Sagnon and M V Sharakhova and T Shea and F A Simão and F Simard and M A Slotman and P Somboon and V Stegniy and C J Struchiner and G W C Thomas and M Tojo and P Topalis and J M C Tubio and M F Unger and J Vontas and C Walton and C S Wilding and J H Willis and Y-C Wu and G Yan and E M Zdobnov and X Zhou and Flaminia Catteruccia and Georges K Christophides and F H Collins and R S Cornman and Andrea Crisanti and M J Donnelly and S J Emrich and M C Fontaine and W Gelbart and M W Hahn and I A Hansen and P I Howell and Fotis C Kafatos and M Kellis and D Lawson and C Louis and S Luckhart and M A T Muskavitch and J M Ribeiro and M A Riehle and I V Sharakhov and Z Tu and L J Zwiebel and N J Besansky},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25554792},
year = {2015},
date = {2015-01-02},
journal = {Science},
volume = {347},
number = {6217},
pages = {1258522},
abstract = {Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.},
keywords = {Anopheles, blandin, genomes, M3i},
pubstate = {published},
tppubtype = {article}
}
Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.
Hammond Andrew, Galizi Roberto, Kyrou Kyros, Simoni Alekos, Siniscalchi Carla, Katsanos Dimitris, Gribble Matthew, Baker Dean, Marois Eric, Russell Steven, Burt Austin, Windbichler Nikolai, Crisanti Andrea, Nolan Tony
A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae Article de journal
Dans: Nature Biotechnology, vol. 34, no. 1, p. 78–83, 2015, ISSN: 1087-0156, 1546-1696.
Liens | BibTeX | Étiquettes: M3i, marois
@article{hammond_crispr-cas9_2015,
title = {A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae},
author = {Andrew Hammond and Roberto Galizi and Kyros Kyrou and Alekos Simoni and Carla Siniscalchi and Dimitris Katsanos and Matthew Gribble and Dean Baker and Eric Marois and Steven Russell and Austin Burt and Nikolai Windbichler and Andrea Crisanti and Tony Nolan},
url = {http://www.nature.com/doifinder/10.1038/nbt.3439},
doi = {10.1038/nbt.3439},
issn = {1087-0156, 1546-1696},
year = {2015},
date = {2015-01-01},
urldate = {2016-01-26},
journal = {Nature Biotechnology},
volume = {34},
number = {1},
pages = {78--83},
keywords = {M3i, marois},
pubstate = {published},
tppubtype = {article}
}
Brunke Sascha, Quintin Jessica, Kasper Lydia, Jacobsen Ilse D, Richter Martin E, Hiller Ekkehard, Schwarzmüller Tobias, d'Enfert Christophe, Kuchler Karl, Rupp Steffen, Hube Bernhard, Ferrandon Dominique
Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts Article de journal
Dans: Dis Model Mech, vol. 8, no. 5, p. 473–486, 2015, ISSN: 1754-8411.
Résumé | Liens | BibTeX | Étiquettes: Alternative infection models, Candida glabrata, ferrandon, Fungal virulence factors, M3i, Mutant library, Signature-tagged mutagenesis
@article{brunke_mice_2015b,
title = {Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts},
author = {Sascha Brunke and Jessica Quintin and Lydia Kasper and Ilse D Jacobsen and Martin E Richter and Ekkehard Hiller and Tobias Schwarzmüller and Christophe d'Enfert and Karl Kuchler and Steffen Rupp and Bernhard Hube and Dominique Ferrandon},
url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415897/},
doi = {10.1242/dmm.019901},
issn = {1754-8411},
year = {2015},
date = {2015-01-01},
journal = {Dis Model Mech},
volume = {8},
number = {5},
pages = {473--486},
abstract = {Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.},
keywords = {Alternative infection models, Candida glabrata, ferrandon, Fungal virulence factors, M3i, Mutant library, Signature-tagged mutagenesis},
pubstate = {published},
tppubtype = {article}
}
Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.
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,