Publications
2015 |
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Book Chapters |
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5. | Majzoub, Karim; Imler, Jean-Luc Encyclopedia of Molecular Cell Biology and Molecular Medicine Book Chapter Verlag, Wiley-VCH (Ed.): 1 , Chapitre « RNAi to treat virus infections », p. 192-228, GmbH & Co. KGaA, 2015. Résumé | Liens | BibTeX | Étiquettes: antiviral, argonaute, delivery, Immunity, lipofection, 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, Immunity, lipofection, 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. |
2013 |
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Articles de journaux |
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4. | Petrillo, Jessica E; Venter, Arno P; Short, James R; Gopal, Radhika ; Deddouche, Safia ; Lamiable, Olivier ; Imler, Jean-Luc ; Schneemann, Anette Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2 Article de journal Journal of Virology, 87 (24), p. 13409–13421, 2013, ISSN: 1098-5514. Résumé | Liens | BibTeX | Étiquettes: Capsid Proteins, Cell Line, Cricetinae, Cytoplasmic Granules, Double-Stranded, Nodaviridae, Protein Biosynthesis, RNA, RNA Virus Infections, RNA-Binding Proteins, Viral, Viral Proteins @article{petrillo_cytoplasmic_2013, title = {Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2}, author = { Jessica E. Petrillo and P. Arno Venter and James R. Short and Radhika Gopal and Safia Deddouche and Olivier Lamiable and Jean-Luc Imler and Anette Schneemann}, doi = {10.1128/JVI.02362-13}, issn = {1098-5514}, year = {2013}, date = {2013-12-01}, journal = {Journal of Virology}, volume = {87}, number = {24}, pages = {13409--13421}, abstract = {Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is conveniently propagated in Drosophila melanogaster cells but can also be grown in mammalian cells. It was previously reported that B2 is dispensable for FHV RNA replication in BHK21 cells; therefore, we chose this cell line to generate a viral mutant that lacked the ability to produce B2. Consistent with published results, we found that RNA replication was indeed vigorous but the yield of progeny virus was negligible. Closer inspection revealed that infected cells contained very small amounts of coat protein despite an abundance of RNA2. B2 mutants that had reduced affinity for dsRNA produced analogous results, suggesting that the dsRNA binding capacity of B2 somehow played a role in coat protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we discovered that RNA2 is recruited into large cytoplasmic granules in the absence of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude that B2, by binding to double-stranded regions in progeny RNA2, prevents recruitment of RNA2 into cellular structures, where it is translationally silenced. This represents a novel function of B2 that further contributes to successful completion of the nodaviral life cycle.}, keywords = {Capsid Proteins, Cell Line, Cricetinae, Cytoplasmic Granules, Double-Stranded, Nodaviridae, Protein Biosynthesis, RNA, RNA Virus Infections, RNA-Binding Proteins, Viral, Viral Proteins}, pubstate = {published}, tppubtype = {article} } Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is conveniently propagated in Drosophila melanogaster cells but can also be grown in mammalian cells. It was previously reported that B2 is dispensable for FHV RNA replication in BHK21 cells; therefore, we chose this cell line to generate a viral mutant that lacked the ability to produce B2. Consistent with published results, we found that RNA replication was indeed vigorous but the yield of progeny virus was negligible. Closer inspection revealed that infected cells contained very small amounts of coat protein despite an abundance of RNA2. B2 mutants that had reduced affinity for dsRNA produced analogous results, suggesting that the dsRNA binding capacity of B2 somehow played a role in coat protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we discovered that RNA2 is recruited into large cytoplasmic granules in the absence of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude that B2, by binding to double-stranded regions in progeny RNA2, prevents recruitment of RNA2 into cellular structures, where it is translationally silenced. This represents a novel function of B2 that further contributes to successful completion of the nodaviral life cycle. |
3. | Kemp, Cordula; Mueller, Stefanie ; Goto, Akira ; Barbier, Vincent ; Paro, Simona ; Bonnay, François ; Dostert, Catherine ; Troxler, Laurent ; Hetru, Charles ; Meignin, Carine ; Pfeffer, Sébastien ; Hoffmann, Jules A; Imler, Jean-Luc Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila Article de journal Journal of Immunology (Baltimore, Md.: 1950), 190 (2), p. 650–658, 2013, ISSN: 1550-6606. Résumé | Liens | BibTeX | Étiquettes: Alphavirus, Alphavirus Infections, bioinformatic, DNA Virus Infections, Gene Expression Regulation, Genetically Modified, Janus Kinases, Male, Nodaviridae, Ribonuclease III, RNA Helicases, RNA Interference, RNA Virus Infections, Transcription Factors @article{kemp_broad_2013, title = {Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila}, author = { Cordula Kemp and Stefanie Mueller and Akira Goto and Vincent Barbier and Simona Paro and François Bonnay and Catherine Dostert and Laurent Troxler and Charles Hetru and Carine Meignin and Sébastien Pfeffer and Jules A. Hoffmann and Jean-Luc Imler}, doi = {10.4049/jimmunol.1102486}, issn = {1550-6606}, year = {2013}, date = {2013-01-01}, journal = {Journal of Immunology (Baltimore, Md.: 1950)}, volume = {190}, number = {2}, pages = {650--658}, abstract = {The fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. The response of Drosophila to virus infections remains poorly characterized and appears to involve two facets. On the one hand, RNA interference involves the recognition and processing of dsRNA into small interfering RNAs by the host RNase Dicer-2 (Dcr-2), whereas, on the other hand, an inducible response controlled by the evolutionarily conserved JAK-STAT pathway contributes to the antiviral host defense. To clarify the contribution of the small interfering RNA and JAK-STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type and mutant for Dcr-2 or the JAK kinase Hopscotch to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by Drosophila C virus and cricket paralysis virus, two members of the Dicistroviridae family, which contrasts with the susceptibility of Dcr-2 mutant flies to many viruses, including the DNA virus invertebrate iridescent virus 6. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by Drosophila C virus or by two unrelated RNA viruses, Flock House virus and Sindbis virus. Overall, our data reveal that RNA interference is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK-STAT pathway appears to be virus specific.}, keywords = {Alphavirus, Alphavirus Infections, bioinformatic, DNA Virus Infections, Gene Expression Regulation, Genetically Modified, Janus Kinases, Male, Nodaviridae, Ribonuclease III, RNA Helicases, RNA Interference, RNA Virus Infections, Transcription Factors}, pubstate = {published}, tppubtype = {article} } The fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. The response of Drosophila to virus infections remains poorly characterized and appears to involve two facets. On the one hand, RNA interference involves the recognition and processing of dsRNA into small interfering RNAs by the host RNase Dicer-2 (Dcr-2), whereas, on the other hand, an inducible response controlled by the evolutionarily conserved JAK-STAT pathway contributes to the antiviral host defense. To clarify the contribution of the small interfering RNA and JAK-STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type and mutant for Dcr-2 or the JAK kinase Hopscotch to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by Drosophila C virus and cricket paralysis virus, two members of the Dicistroviridae family, which contrasts with the susceptibility of Dcr-2 mutant flies to many viruses, including the DNA virus invertebrate iridescent virus 6. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by Drosophila C virus or by two unrelated RNA viruses, Flock House virus and Sindbis virus. Overall, our data reveal that RNA interference is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK-STAT pathway appears to be virus specific. |
2009 |
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Articles de journaux |
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2. | Kemp, Cordula; Imler, Jean-Luc Antiviral immunity in drosophila Article de journal Current Opinion in Immunology, 21 (1), p. 3–9, 2009, ISSN: 1879-0372. Résumé | Liens | BibTeX | Étiquettes: Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence @article{kemp_antiviral_2009, title = {Antiviral immunity in drosophila}, author = { Cordula Kemp and Jean-Luc Imler}, doi = {10.1016/j.coi.2009.01.007}, issn = {1879-0372}, year = {2009}, date = {2009-02-01}, journal = {Current Opinion in Immunology}, volume = {21}, number = {1}, pages = {3--9}, abstract = {Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals.}, keywords = {Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence}, pubstate = {published}, tppubtype = {article} } Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals. |
2007 |
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Articles de journaux |
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1. | Müller, Stefanie; Imler, Jean-Luc Dicing with viruses: microRNAs as antiviral factors Article de journal Immunity, 27 (1), p. 1–3, 2007, ISSN: 1074-7613. Résumé | Liens | BibTeX | Étiquettes: DEAD-box RNA Helicases, Endoribonucleases, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections @article{muller_dicing_2007, title = {Dicing with viruses: microRNAs as antiviral factors}, author = { Stefanie Müller and Jean-Luc Imler}, doi = {10.1016/j.immuni.2007.07.003}, issn = {1074-7613}, year = {2007}, date = {2007-07-01}, journal = {Immunity}, volume = {27}, number = {1}, pages = {1--3}, abstract = {In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV.}, keywords = {DEAD-box RNA Helicases, Endoribonucleases, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections}, pubstate = {published}, tppubtype = {article} } In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV. |
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