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7. Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase

Author

Bonnard, Damien, primary, Le Rouzic, Erwann, additional, Singer, Matthew R., additional, Yu, Zhe, additional, Le Strat, Frédéric, additional, Batisse, Claire, additional, Batisse, Julien, additional, Amadori, Céline, additional, Chasset, Sophie, additional, Pye, Valerie E., additional, Emiliani, Stéphane, additional, Ledoussal, Benoit, additional, Ruff, Marc, additional, Moreau, François, additional, Cherepanov, Peter, additional, and Benarous, Richard, additional

Published
2023
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9. Premature transcription termination complex proteins PCF11 and WDR82 silence HIV-1 expression in latently infected cells.

Author

Said, Melissa Ait, Bejjani, Fabienne, Abdouni, Ahmed, Ségéral, Emmanuel, and Emiliani, Stéphane

Subjects
HIV, RNA polymerase II
Abstract

Postintegration transcriptional silencing of HIV-1 leads to the establishment of a pool of latently infected cells. In these cells, mechanisms controlling RNA Polymerase II (RNAPII) pausing and premature transcription termination (PTT) remain to be explored. Here, we found that the cleavage and polyadenylation (CPA) factor PCF11 represses HIV-1 expression independently of the other subunits of the CPA complex or the polyadenylation signal located at the 5' LTR. We show that PCF11 interacts with the RNAPII-binding protein WDR82. Knock-down of PCF11 or WDR82 reactivated HIV-1 expression in latently infected cells. To silence HIV-1 transcription, PCF11 and WDR82 are specifically recruited at the promoter-proximal region of the provirus in an interdependent manner. Codepletion of PCF11 and WDR82 indicated that they act on the same pathway to repress HIV expression. These findings reveal PCF11/WDR82 as a PTT complex silencing HIV-1 expression in latently infected cells. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Biological and structural analysis of new potent Integrase-LEDGF allosteric HIV-1 inhibitors

Author

Le Rouzic, Erwann, primary, Bonnard, Damien, additional, Le Strat, Frédéric, additional, Batisse, Claire, additional, Batisse, Julien, additional, Amadori, Céline, additional, Chasset, Sophie, additional, Emiliani, Stéphane, additional, Ledoussal, Benoit, additional, Ruff, Marc, additional, Moreau, François, additional, and Benarous, Richard, additional

Published
2023
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15. Additional file 1 of DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence

Author

Lista, María José, Jousset, Anne-Caroline, Cheng, Mingpan, Saint-André, Violaine, Perrot, Elouan, Rodrigues, Melissa, Di Primo, Carmelo, Gadelle, Danielle, Toccafondi, Elenia, Segeral, Emmanuel, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, Mergny, Jean-Louis, and Lavigne, Marc

Abstract

Additional file 1: Figure S1. DNA topoisomerases shRNA silencing and CRISPR/Cas9 edition in J-Lat A1 cells. Representative western blots and mRNA quantification of topoisomerases in shRNA-silenced and CRISPR-edited J-Lat A1 cells. All experiments were repeated at least 3 times.

Published
2023
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16. Additional file 3 of DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence

Author

Lista, María José, Jousset, Anne-Caroline, Cheng, Mingpan, Saint-André, Violaine, Perrot, Elouan, Rodrigues, Melissa, Di Primo, Carmelo, Gadelle, Danielle, Toccafondi, Elenia, Segeral, Emmanuel, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, Mergny, Jean-Louis, and Lavigne, Marc

Abstract

Additional file 3: Figure S3. Y723F mutation does not affect TOP1 interaction to HIV-1 LTR III G4 structure. Jurkat cells were transduced by a pTRIP vector expressing WT or Y723F TOP1. 8 days post transduction, total extracts of these cells were used for G4 pull-down assays, similarly as in Fig. 5B, C. This experiment was repeated at least 3 times.

Published
2023
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17. Additional file 4 of DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence

Author

Lista, María José, Jousset, Anne-Caroline, Cheng, Mingpan, Saint-André, Violaine, Perrot, Elouan, Rodrigues, Melissa, Di Primo, Carmelo, Gadelle, Danielle, Toccafondi, Elenia, Segeral, Emmanuel, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, Mergny, Jean-Louis, and Lavigne, Marc

Abstract

Additional file 4: Figure S4. No G4 enrichment is observed in the positive or negative strands of TOP1 activated genes of HCT116 cells. G4 predictions in the promoter sequence of human genes repressed by Top1. Boxplots of G4 maximum scoresin positive or negative strand at the TSS-500 bp-TSS of genes that are significantly down-regulated or for a same number of genes which RNA levels are not modified in shTop1 versus shCtrl HCT116 cells.

Published
2023
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18. Additional file 5 of DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence

Author

Lista, María José, Jousset, Anne-Caroline, Cheng, Mingpan, Saint-André, Violaine, Perrot, Elouan, Rodrigues, Melissa, Di Primo, Carmelo, Gadelle, Danielle, Toccafondi, Elenia, Segeral, Emmanuel, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, Mergny, Jean-Louis, and Lavigne, Marc

Abstract

Additional file 5: Table S1. Sequence of the oligonucleotides used in this study.

Published
2023
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20. Additional file 5 of Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection

Author

Quang, Nam Nguyen, Goudey, Sophie, Ségéral, Emmanuel, Ammara Mohammad, Lemoine, Sophie, Blugeon, Corinne, Versapuech, Margaux, Jean-Christophe Paillart, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, and Gallois-Montbrun, Sarah

Subjects
viruses, parasitic diseases
Abstract

Additional file 5: Figure S1. Viral isoform levels in different models of HIV-1 expressing cells. (a) Exon combinations identified by ONT sequencing in infected T cells (INF T cells), transfected (TF HeLa) or infected (INF HeLa) HeLa cells. (b) Exon combinations ≥5 copies amongst replicates and considered as existing viral isoforms in the rest of the analysis.

Published
2020
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21. Additional file 8 of Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection

Author

Quang, Nam Nguyen, Goudey, Sophie, Ségéral, Emmanuel, Ammara Mohammad, Lemoine, Sophie, Blugeon, Corinne, Versapuech, Margaux, Jean-Christophe Paillart, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, and Gallois-Montbrun, Sarah

Abstract

Additional file 8: Figure S3. Estimation of the relative abundance of HIV-1 mRNA size classes using ONT sequencing. (a) Schematic representation of HIV-1 unspliced (US, 9-kb), incompletely spliced (IS, 4-kb) and multiply-spliced (MS, 2-kb) classes of HIV-1 RNA. SS used to calculate the levels of HIV-1 classes are indicated. Excised introns are represented as dotted lines and conserved exons as filled lines. Complete sequencing reads (CSR) corresponding to annotated reads starting before D1, ending after D4 and harbouring a least one splice junction involving D1 are indicated. (b) Relative quantification of MS and IS isoforms were calculated by dividing the number of CSR including (2-kb) or not (4-kb) a splice junction at D4 by the total number of CSR. (c) Relative quantification of 9-kb and spliced RNAs at D1 were estimated by counting the number of reads splicing (2-kb+4-kb) or not (9-kb) at D1 by the total number of reads passing through D1. (d) Relative quantification of 2-kb and 9-kb or 4-kb RNAs were estimated by counting the number of reads splicing (2-kb) or not (4-kb+9-kb) at D4 by the total number of reads passing through D4. Relative level of 9-kb, 4-kb and 2-kb RNAs in Fig. 3 was estimated by integrating the levels of each class determined in (b), (c) and (d).

Published
2020
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22. Additional file 15 of Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection

Author

Quang, Nam Nguyen, Goudey, Sophie, Ségéral, Emmanuel, Ammara Mohammad, Lemoine, Sophie, Blugeon, Corinne, Versapuech, Margaux, Jean-Christophe Paillart, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, and Gallois-Montbrun, Sarah

Subjects
viruses, virus diseases, biochemical phenomena, metabolism, and nutrition
Abstract

Additional file 15: Figure S8. Relative abundance of viral transcripts expressed at early time points of HIV-1 infection in CD4+ T cells, determined by ONT sequencing. Abundance of all viral transcripts expressed in CD4+ T cells from donor 4 between 12 h and 24 hpi was determined as in Fig. 6. Each panel corresponds to a family of transcripts: (a) Nef, (b) Env/Vpu, (c) Vpr, (d) Rev, (e) Tat and (f) Vif.

Published
2020
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23. Additional file 6 of Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection

Author

Quang, Nam Nguyen, Goudey, Sophie, Ségéral, Emmanuel, Ammara Mohammad, Lemoine, Sophie, Blugeon, Corinne, Versapuech, Margaux, Jean-Christophe Paillart, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, and Gallois-Montbrun, Sarah

Abstract

Additional file 6: Figure S2. Identification of new and rare transcripts involving SS D1c, D4a, A1b, A5a and A5c and LTR2 RNA in HIV-1 infected T cell samples. (a) IGV screenshots of ONT read alignments of new and rare transcripts described in the Additional file 4: Table S4. (b) New and rare transcripts were reverse transcribed and amplified using specific primers (Additional file 16: Table S8). DNA sequencing chromatograms of confirmed junctions are presented.

Published
2020
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24. Additional file 9 of Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection

Author

Quang, Nam Nguyen, Goudey, Sophie, Ségéral, Emmanuel, Ammara Mohammad, Lemoine, Sophie, Blugeon, Corinne, Versapuech, Margaux, Jean-Christophe Paillart, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, and Gallois-Montbrun, Sarah

Abstract

Additional file 9: Figure S4. Correlation of viral isoform abundances quantified by ONT sequencing between T cell replicates. The relative abundances of HIV-1 spliced RNAs were calculated as a % of the total number of spliced viral RNAs. Results were compared between infected T cell samples obtained from 3 different donors using a linear regression model supplied by Prism 7: (a) donor 1 vs donor 2; (b) donor 1 vs donor 3; (c) donor 2 vs donor 3. Pearson correlation coefficients r are indicated. p

Published
2020
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32. YTHDC1 regulates distinct post-integration steps of HIV-1 replication and is important for viral infectivity.

Author

N'Da Konan, Sarah, Ségéral, Emmanuel, Bejjani, Fabienne, Bendoumou, Maryam, Ait Said, Mélissa, Gallois-Montbrun, Sarah, and Emiliani, Stéphane

Subjects
HIV, GENETIC regulation, RNA splicing, RNA modification & restriction, VIRAL proteins
Abstract

Background: The recent discovery of the role of m6A methylation in the regulation of HIV-1 replication unveiled a novel layer of regulation for HIV gene expression. This epitranscriptomic modification of HIV-1 RNAs is under the dynamic control of specific writers and erasers. In addition, cytoplasmic readers of the m6A mark are recruited to the modified viral RNAs and regulate HIV-1 replication. Yet, little is known about the effects of m6A writers and readers on the biogenesis of HIV-1 RNAs. Results: We showed that the METTL3/14 m6A methyltransferase complex and the m6A YTHDF2 cytoplasmic writer down regulates the abundance of HIV-1 RNAs in infected cells. We also identified the m6A nuclear writer YTHDC1 as a novel regulator of HIV-1 transcripts. In HIV-1 producer cells, we showed that knocking down YTHDC1 increases the levels of unspliced and incompletely spliced HIV-1 RNAs, while levels of multiply spliced transcripts remained unaffected. In addition, we observed that depletion of YTHDC1 has no effect on the nuclear cytoplasmic distribution of viral transcripts. YTHDC1 binds specifically to HIV-1 transcripts in a METTL3-dependent manner. Knocking down YTHDC1 reduces the expression of Env and Vpu viral proteins in producer cells and leads to the incorporation of unprocessed Env gp160 in virus particles, resulting in the decrease of their infectivity. Conclusions: Our findings indicate that, by controlling HIV-1 RNA biogenesis and protein expression, the m6A nuclear reader YTHDC1 is required for efficient production of infectious viral particles. [ABSTRACT FROM AUTHOR]

Published
2022
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33. Identification of low molecular weight nuclear complexes containing integrase during the early stages of HIV-1 infection

Author

Gérard Annabelle, Soler Nicolas, Ségéral Emmanuel, Belshan Michael, and Emiliani Stéphane

Subjects
Human immunodeficiency virus, Integrase, Pre-integration complex, LEDGF/p75, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background HIV-1 replication requires integration of its reverse transcribed viral cDNA into a host cell chromosome. The DNA cutting and joining reactions associated to this key step are catalyzed by the viral protein integrase (IN). In infected cells, IN binds the viral cDNA, together with viral and cellular proteins, to form large nucleoprotein complexes. However, the dynamics of IN complexes formation is still poorly understood. Results Here, we characterized IN complexes during the early stages of T-lymphocyte infection. We found that following viral entry into the host cell, IN was rapidly targeted to proteasome-mediated degradation. Interactions between IN and cellular cofactors LEDGF/p75 and TNPO3 were detected as early as 6 h post-infection. Size exclusion chromatography of infected cell extracts revealed distinct IN complexes in vivo. While at 2 h post-infection the majority of IN eluted within a high molecular weight complex competent for integration (IN complex I), IN was also detected in a low molecular weight complex devoid of full-length viral cDNA (IN complex II, ~440 KDa). At 6 h post-infection the relative proportion of IN complex II increased. Inhibition of reverse transcription or integration did not alter the elution profile of IN complex II in infected cells. However, in cells depleted for LEDGF/p75 IN complex II shifted to a lower molecular weight complex (IN complex III, ~150 KDa) containing multimers of IN. Notably, cell fractionation experiments indicated that both IN complex II and III were exclusively nuclear. Finally, IN complex II was not detected in cells infected with a virus harboring a mutated IN defective for LEDGF/p75 interaction and tetramerization. Conclusions Our findings indicate that, shortly after viral entry, a significant portion of DNA–free IN that is distinct from active pre-integration complexes accumulates in the nucleus.

Published
2013
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35. Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import

Author

Cribier Alexandra, Ségéral Emmanuel, Delelis Olivier, Parissi Vincent, Simon Aurélie, Ruff Marc, Benarous Richard, and Emiliani Stéphane

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Integration of human immunodeficiency virus type 1 (HIV-1) into a host cell chromosome is an essential step under the control of the viral integrase (IN). Although this enzyme is necessary and sufficient to catalyze the integration reaction in vitro, cellular cofactors are involved in the process in vivo. The chromatin-associated factor LEDGF/p75 interacts with IN and promotes integration to transcription units of the host genome. HIV-1 IN also binds the karyopherin TNPO3, however the significance of this interaction during viral replication remains to be explored. Results Here we present a functional analysis of IN mutants impaired for LEDGF/p75 and TNPO3 interaction. Among them, IN W131A and IN Q168L, that were previously identified to be deficient for LEDGF/p75 interaction, were also partially impaired for TNPO3 binding. We observed that mutations abolishing IN ability to form tetramers resulted in a severe reduction in LEDGF/p75 binding. In sharp contrast, no correlation could be found between the ability of IN to multimerize and TNPO3 interaction. Most of the mutant viruses were essentially impaired for the integration step whereas the amount of 2-LTR circles, reflecting the nuclear import of the viral DNA, was not significantly affected. Conclusion Our functional analysis of HIV-1 IN mutants reveals distinct structural basis for TNPO3 interaction and suggests that the interaction between IN and TNPO3 is not a major determinant of nuclear import but could take place at a nuclear step prior to integration.

Published
2011
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36. Centrosomal pre-integration latency of HIV-1 in quiescent cells

Author

Emiliani Stéphane, Roingeard Philippe, Tobaly-Tapiero Joëlle, Giron Marie-Lou, Clave Emmanuel, Lehmann-Che Jacqueline, Zamborlini Alessia, Toubert Antoine, de Thé Hugues, and Saïb Ali

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Human immunodeficiency virus type 1 (HIV-1) efficiently replicates in dividing and non-dividing cells. However, HIV-1 infection is blocked at an early post-entry step in quiescent CD4+ T cells in vitro. The molecular basis of this restriction is still poorly understood. Here, we show that in quiescent cells, incoming HIV-1 sub-viral complexes concentrate and stably reside at the centrosome for several weeks. Upon cell activation, viral replication resumes leading to viral gene expression. Thus, HIV-1 can persist in quiescent cells as a stable, centrosome-associated, pre-integration intermediate.

Published
2007
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37. Structure-function analyses unravel distinct effects of allosteric inhibitors of HIV-1 integrase on viral maturation and integration

Author

Bonnard, Damien, primary, Le Rouzic, Erwann, additional, Eiler, Sylvia, additional, Amadori, Céline, additional, Orlov, Igor, additional, Bruneau, Jean-Michel, additional, Brias, Julie, additional, Barbion, Julien, additional, Chevreuil, Francis, additional, Spehner, Danièle, additional, Chasset, Sophie, additional, Ledoussal, Benoit, additional, Moreau, François, additional, Saïb, Ali, additional, Klaholz, Bruno P., additional, Emiliani, Stéphane, additional, Ruff, Marc, additional, Zamborlini, Alessia, additional, and Benarous, Richard, additional

Published
2018
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38. Argonaute proteins regulate HIV-1 multiply spliced RNA and viral production in a Dicer independent manner

Author

Eckenfelder, Agathe, Ségéral, Emmanuel, Pinzón, Natalia, Ulveling, Damien, Amadori, Céline, Charpentier, Marine, Nidelet, Sabine, Concordet, Jean-Paul, Zagury, Jean-François, Paillart, Jc, Berlioz-Torrent, Clarisse, Seitz, Hervé, Emiliani, Stéphane, Gallois-Montbrun, Sarah, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire génomique, bioinformatique et applications (GBA), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Larose, Catherine, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), CNAM, Laboratoire Génomique, Bioinformatique et Applications (EA 4627), Paris 75003, France, Structure et Instabilité des Génomes ( STRING ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Muséum National d'Histoire Naturelle ( MNHN ), Institut de Génomique Fonctionnelle - Montpellier GenomiX ( IGF MGX ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), and Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg 67084, France

Subjects
Ribonuclease III, [SDV]Life Sciences [q-bio], Genome, Viral, [SDV.GEN] Life Sciences [q-bio]/Genetics, DEAD-box RNA Helicases, Jurkat Cells, RNA Precursors, Humans, Immunoprecipitation, RNA, Messenger, Eukaryotic Initiation Factors, ComputingMilieux_MISCELLANEOUS, [SDV.GEN]Life Sciences [q-bio]/Genetics, Binding Sites, [ SDV ] Life Sciences [q-bio], Sequence Analysis, RNA, Virion, High-Throughput Nucleotide Sequencing, [SDV] Life Sciences [q-bio], Alternative Splicing, HEK293 Cells, Argonaute Proteins, HIV-1, RNA, RNA, Viral, RNA Splice Sites, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, HeLa Cells
Abstract

International audience; Argonaute (Ago) proteins associate with microRNAs (miRNAs) to form the core of the RNA-induced silencing complex (RISC) that mediates post-transcriptional gene silencing of target mRNAs. As key players in anti-viral defense, Ago proteins are thought to have the ability to interact with human immunodeficiency virus type 1 (HIV-1) RNA. However, the role of this interaction in regulating HIV-1 replication has been debated. Here, we used high throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) to explore the interaction between Ago2 and HIV-1 RNA in infected cells. By only considering reads of 50 nucleotides length in our analysis, we identified more than 30 distinct binding sites for Ago2 along the viral RNA genome. Using reporter assays, we found four binding sites, located near splice donor sites, capable of repressing Luciferase gene expression in an Ago-dependent manner. Furthermore, inhibition of Ago1 and Ago2 levels in cells expressing HIV-1 led to an increase of viral multiply spliced transcripts and to a strong reduction in the extracellular CAp24 level. Depletion of Dicer did not affect these activities. Our results highlight a new role of Ago proteins in the control of multiply spliced HIV-1 transcript levels and viral production, independently of the miRNA pathway.

Published
2016

39. The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity

Author

Amadori, Céline, primary, van der Velden, Yme Ubeles, additional, Bonnard, Damien, additional, Orlov, Igor, additional, van Bel, Nikki, additional, Le Rouzic, Erwann, additional, Miralles, Laia, additional, Brias, Julie, additional, Chevreuil, Francis, additional, Spehner, Daniele, additional, Chasset, Sophie, additional, Ledoussal, Benoit, additional, Mayr, Luzia, additional, Moreau, François, additional, García, Felipe, additional, Gatell, José, additional, Zamborlini, Alessia, additional, Emiliani, Stéphane, additional, Ruff, Marc, additional, Klaholz, Bruno P., additional, Moog, Christiane, additional, Berkhout, Ben, additional, Plana, Montserrat, additional, and Benarous, Richard, additional

Published
2017
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40. Proceedings of the Frontiers of Retrovirology Conference 2016

Author

Zurnic, Irena, primary, Hütter, Sylvia, additional, Lehmann, Ute, additional, Stanke, Nicole, additional, Reh, Juliane, additional, Kern, Tobias, additional, Lindel, Fabian, additional, Gerresheim, Gesche, additional, Hamann, Martin, additional, Müllers, Erik, additional, Lesbats, Paul, additional, Cherepanov, Peter, additional, Serrao, Erik, additional, Engelman, Alan, additional, Lindemann, Dirk, additional, Da Silva Santos, Claire, additional, Tartour, Kevin, additional, Cimarelli, Andrea, additional, Burdick, Rya, additional, Chen, Jianbo, additional, Sastri, Jaya, additional, Hu, Wei-Shau, additional, Pathak, Vinay, additional, Keppler, Oliver T., additional, Pradeau, Karine, additional, Eiler, Sylvia, additional, Levy, Nicolas, additional, Lennon, Sarah, additional, Cianferani, Sarah, additional, Emiliani, Stéphane, additional, Ruff, Marc, additional, Parissi, Vincent, additional, Rato, Sylvie, additional, Rausell, Antonio, additional, Munoz, Miguel, additional, Telenti, Amalio, additional, Ciuffi, Angela, additional, Zhyvoloup, Alexander, additional, Melamed, Anat, additional, Anderson, Ian, additional, Planas, Delphine, additional, Kriston-Vizi, Janos, additional, Ketteler, Robin, additional, Lee, Chen- Hsuin, additional, Merritt, Andy, additional, Ancuta, Petronela, additional, Bangham, Charles, additional, Fassati, Ariberto, additional, Rodari, Anthony, additional, Van Driessche, Benoit, additional, Galais, Mathilde, additional, Delacourt, Nadége, additional, Fauquenoy, Sylvain, additional, Vanhulle, Caroline, additional, Kula, Anna, additional, Burny, Arsène, additional, Rohr, Olivier, additional, Van Lint, Carine, additional, van Montfort, Thijs, additional, van der Sluis, Renee, additional, Speijer, Dave, additional, Berkhout, Ben, additional, Meng, Bo, additional, Rutkowski, Andrzej, additional, Berry, Neil, additional, Dölken, Lars, additional, Lever, Andrew, additional, Schuster, Thomas, additional, Asbach, Benedikt, additional, Wagner, Ralf, additional, Gross, Christine, additional, Wiesmann, Veit, additional, Kalmer, Martina, additional, Wittenberg, Thomas, additional, Gettemans, Jan, additional, Thoma-Kress, Andrea K., additional, Li, Minghua, additional, Freed, Eric O., additional, Liu, Shan-Lu, additional, Müller, Janis, additional, Münch, Jan, additional, Sewald, Xaver, additional, Uchil, Pradeep, additional, Ladinsky, Mark, additional, Beloor, Jagadish, additional, Pi, Ruoxi, additional, Herrmann, Christin, additional, Motamedi, Nasim, additional, Murooka, Thomas, additional, Brehm, Michael, additional, Greiner, Dale, additional, Mempel, Thorsten, additional, Bjorkman, Pamela, additional, Kumar, Priti, additional, Mothes, Walther, additional, Joas, Simone, additional, Parrish, Erica, additional, Gnanadurai, Clement Wesley, additional, Lump, Edina, additional, Stürzel, Christina M., additional, Parrish, Nicholas F., additional, Sauermann, Ulrike, additional, Töpfer, Katharina, additional, Schultheiss, Tina, additional, Bosinger, Steven, additional, Silvestri, Guido, additional, Apetrei, Cristian, additional, Huot, Nicholas, additional, Müller-Trutwin, Michaela, additional, Sauter, Daniel, additional, Hahn, Beatrice H., additional, Stahl-Hennig, Christiane, additional, Kirchhoff, Frank, additional, Schumann, Gerald, additional, Jung-Klawitter, Sabine, additional, Fuchs, Nina V., additional, Upton, Kyle R., additional, Muñoz-Lopez, Martin, additional, Shukla, Ruchi, additional, Wang, Jichang, additional, Garcia-Canadas, Marta, additional, Lopez-Ruiz, Cesar, additional, Gerhardt, Daniel J., additional, Sebe, Attila, additional, Grabundzija, Ivana, additional, Gerdes, Patricia, additional, Merkert, Sylvia, additional, Pulgarin, Andres, additional, Bock, Anja, additional, Held, Ulrike, additional, Witthuhn, Anett, additional, Haase, Alexandra, additional, Wolvetang, Ernst J., additional, Martin, Ulrich, additional, Ivics, Zoltán, additional, Izsvák, Zsuzsanna, additional, Garcia-Perez, J., additional, Faulkner, Geoffrey J., additional, Hurst, Tara, additional, Katzourakis, Aris, additional, Magiorkinis, Gkikas, additional, Schott, Kerstin, additional, Derua, Rita, additional, Seifried, Janna, additional, Reuter, Andreas, additional, Schmitz, Heike, additional, Tondera, Christiane, additional, Brandariz-Nuñez, Alberto, additional, Diaz-Griffero, Felipe, additional, Janssens, Veerle, additional, König, Renate, additional, Baldauf, Hanna-Mari, additional, Stegmann, Lena, additional, Schwarz, Sarah-Marie, additional, Trotard, Maud, additional, Martin, Margarethe, additional, Lenzi, Gina, additional, Burggraf, Manja, additional, Pan, Xiaoyu, additional, Fregoso, Oliver I., additional, Lim, Efrem S., additional, Abraham, Libin, additional, Erikson, Elina, additional, Nguyen, Laura, additional, Ambiel, Ina, additional, Rutsch, Frank, additional, Kim, Baek, additional, Emerman, Michael, additional, Fackler, Oliver T., additional, Wittmann, Sabine, additional, Behrendt, Rayk, additional, Volkmann, Bianca, additional, Eissmann, Kristin, additional, Gramberg, Thomas, additional, Bolduan, Sebastian, additional, Koppensteiner, Herwig, additional, Regensburg, Stefanie, additional, Brack-Werner, Ruth, additional, Draenert, Rika, additional, Schindler, Michael, additional, Ducroux, Aurélie, additional, Xu, Shuting, additional, Ponnurangam, Aparna, additional, Franz, Sergej, additional, Malassa, Angelina, additional, Ewald, Ellen, additional, Goffinet, Christine, additional, Fung, Sin-Yee, additional, Chan, Ching-Ping, additional, Yuen, Chun-Kit, additional, Kok, Kin-Hang, additional, Chan, Chin-Ping, additional, Jin, Dong-Yan, additional, Dittmer, Ulf, additional, Kmiec, Dorota, additional, Iyer, Shilpa, additional, Stürzel, Christina, additional, Hahn, Beatrice, additional, Ariumi, Yasuo, additional, Yasuda-Inoue, Mariko, additional, Kawano, Koudai, additional, Tateishi, Satoshi, additional, Turelli, Priscilla, additional, Compton, Alex, additional, Roy, Nicolas, additional, Porrot, Françoise, additional, Billet, Anne, additional, Casartelli, Nicoletta, additional, Yount, Jacob, additional, Liang, Chen, additional, Schwartz, Oliver, additional, Magnus, Carsten, additional, Reh, Lucia, additional, Moore, Penny, additional, Uhr, Therese, additional, Weber, Jacqueline, additional, Morris, Lynn, additional, Trkola, Alexandra, additional, Grindberg, Rashel V., additional, Schlaepfer, Erika, additional, Schreiber, Gideon, additional, Simon, Viviana, additional, Speck, Roberto F., additional, Debyser, Zeger, additional, Vranckx, Lenard, additional, Demeulemeester, Jonas, additional, Saleh, Suha, additional, Verdin, Eric, additional, Cereseto, Anna, additional, Christ, Frauke, additional, Gijsbers, Rik, additional, Wang, Gang, additional, Zhao, Na, additional, Das, Atze T., additional, Köstler, Josef, additional, Perdiguero, Beatriz, additional, Esteban, Mariano, additional, Jacobs, Bertram L., additional, Montefiori, David C., additional, LaBranche, Celia C., additional, Yates, Nicole L., additional, Tomaras, Georgia D., additional, Ferrari, Guido, additional, Foulds, Kathryn E., additional, Roederer, Mario, additional, Landucci, Gary, additional, Forthal, Donald N., additional, Seaman, Michael S., additional, Hawkins, Natalie, additional, Self, Steven G., additional, Phogat, Sanjay, additional, Tartaglia, James, additional, Barnett, Susan W., additional, Burke, Brian, additional, Cristillo, Anthony D., additional, Ding, Song, additional, Heeney, Jonathan L., additional, Pantaleo, Giuseppe, additional, Stab, Viktoria, additional, Ensser, Armin, additional, Tippler, Bettina, additional, Burton, Dennis, additional, Tenbusch, Matthias, additional, Überla, Klaus, additional, Alter, Galit, additional, Lofano, Giuseppe, additional, Dugast, Anne-Sophie, additional, Kulkarni, Viraj, additional, Suscovich, Todd, additional, Opazo, Tatiana, additional, Barraza, Felipe, additional, Herrera, Diego, additional, Garces, Andrea, additional, Schwenke, Tomas, additional, Tapia, Diego, additional, Cancino, Jorge, additional, Arriagada, Gloria, additional, Haußner, Christina, additional, Damm, Dominik, additional, Rohrhofer, Anette, additional, Schmidt, Barbara, additional, Eichler, Jutta, additional, Midgley, Rebecca, additional, Wheeldon, James, additional, Piguet, Vincent, additional, Khopkar, Priyanka, additional, Rohamare, Megha, additional, Kulkarni, Smita, additional, Godinho-Santos, Ana, additional, Hance, Allan, additional, Goncalves, Joao, additional, Mammano, Fabrizio, additional, Gasser, Romain, additional, Hamoudi, Meriem, additional, Pellicciotta, Martina, additional, Zhou, Zhicheng, additional, Visdeloup, Clara, additional, Colin, Philippe, additional, Braibant, Martine, additional, Lagane, Bernard, additional, Negroni, Matteo, additional, Wamara, Jula, additional, Bannert, Norbert, additional, Mesplede, Thibault, additional, Osman, Nathan, additional, Anstett, Kaitlin, additional, Liang, Jiaming Calvin, additional, Pham, Hanh Thi, additional, Wainberg, Mark, additional, Shao, Wei, additional, Shan, Jigui, additional, Kearney, Mary, additional, Wu, Xiaolin, additional, Maldarelli, Frank, additional, Mellors, John, additional, Luke, Brian, additional, Coffin, John, additional, Hughes, Stephen, additional, Fricke, Thomas, additional, Opp, Silvana, additional, Shepard, Caitlin, additional, Ivanov, Dmitri, additional, Valle-Casuso, Jose, additional, Kanja, Marine, additional, Cappy, Pierre, additional, Lener, Daniela, additional, Knyazhanskaya, Ekaterina, additional, Anisenko, Andrey, additional, Zatsepin, Timofey, additional, Gottikh, Marina, additional, Komkov, Alexander, additional, Minervina, Anastasia, additional, Nugmanov, Gaiaz, additional, Nazarov, Vadim, additional, Khodosevich, Konstantin, additional, Mamedov, Ilgar, additional, Lebedev, Yuri, additional, Colomer-Lluch, Marta, additional, Serra-Moreno, Ruth, additional, Sarracino, Ambra, additional, Gharu, Lavina, additional, Pasternak, Alexander, additional, Marcello, Alessandro, additional, McCartin, Ann Marie, additional, Kulkarni, Anurag, additional, Le Douce, Valentin, additional, Gautier, Virginie, additional, Baeyens, Ann, additional, Naessens, Evelien, additional, Van Nuffel, Anouk, additional, Weening, Karin, additional, Reilly, Anne- Marie, additional, Claeys, Eva, additional, Trypsteen, Wim, additional, Vandekerckhove, Linos, additional, Eyckerman, Sven, additional, Gevaert, Kris, additional, Verhasselt, Bruno, additional, Mok, Hoi Ping, additional, Norton, Nicholas, additional, Fun, Axel, additional, Hirst, Jack, additional, Wills, Mark, additional, Miklik, Dalibor, additional, Senigl, Filip, additional, Hejnar, Jiri, additional, Sakuragi, Jun-ichi, additional, Sakuragi, Sayuri, additional, Yokoyama, Masaru, additional, Shioda, Tatsuo, additional, Sato, Hironori, additional, Bodem, Jochen, additional, Moschall, Rebecca, additional, Denk, Sarah, additional, Erkelenz, Steffen, additional, Schenk, Christian, additional, Schaal, Heiner, additional, Donhauser, Norbert, additional, Socher, Ellen, additional, Millen, Sebastian, additional, Sticht, Heinrich, additional, Mann, Melanie, additional, Wei, Guochao, additional, Betts, Matthew J., additional, Liu, Yang, additional, Kehl, Timo, additional, Russell, Robert B., additional, Löchelt, Martin, additional, Hohn, Oliver, additional, Mostafa, Saeed, additional, Hanke, Kirsten, additional, Norley, Stephen, additional, Chen, Chia-Yen, additional, Shingai, Masashi, additional, Borrego, Pedro, additional, Taveira, Nuno, additional, Strebel, Klaus, additional, Hellmund, Chris, additional, Friedrich, Melanie, additional, Hahn, Friedrich, additional, Setz, Christian, additional, Rauch, Pia, additional, Fraedrich, Kirsten, additional, Matthaei, Alina, additional, Henklein, Petra, additional, Traxdorf, Maximilian, additional, Fossen, Torgils, additional, Schubert, Ulrich, additional, Khwaja, Aya, additional, Galilee, Meytal, additional, Alian, Akram, additional, Schwalbe, Birco, additional, Hauser, Heiko, additional, Schreiber, Michael, additional, Scherpenisse, Mirte, additional, Cho, Young-Keol, additional, Kim, Jungeun, additional, Jeong, Daeun, additional, Trejbalova, Katerina, additional, Benesova, Martina, additional, Kucerova, Dana, additional, Vernerova, Zdenka, additional, Amouroux, Rachel, additional, Hajkova, Petra, additional, Elleder, Daniel, additional, Hron, Tomas, additional, Farkasova, Helena, additional, Padhi, Abinash, additional, Paces, Jan, additional, Zhu, Henan, additional, Gifford, Robert, additional, Murcia, Pablo, additional, Carrozza, Maria Luisa, additional, Niewiadomska, Anna-Maria, additional, Mazzei, Maurizio, additional, Abi-Said, Mounir, additional, Hughes, Joseph, additional, Hué, Stéphane, additional, Obasa, Adetayo, additional, Jacobs, Graeme, additional, Engelbrecht, Susan, additional, Mack, Katharina, additional, Starz, Kathrin, additional, Geyer, Matthias, additional, Bibollet-Ruche, Frederic, additional, Leoz, Marie, additional, Plantier, Jean Christophe, additional, Argaw-Denboba, Ayele, additional, Balestrieri, Emanuela, additional, Serafino, Annalucia, additional, Bucci, Ilaria, additional, Cipriani, Chiara, additional, Spadafora, Corrado, additional, Sinibaldi-Vallebona, Paolo, additional, Matteucci, Claudia, additional, Jayashree, S. Nandi, additional, Neogi, Ujjwal, additional, Chhangani, Anil K., additional, Rathore, Shravan Sing, additional, Mathur, Bajrang R. J., additional, Abati, Adeyemi, additional, Koç, B. Taylan, additional, Oğuzoğlu, Tuba Çiğdem, additional, Shimauchi, Takatoshi, additional, Caucheteux, Stephan, additional, Turpin, Jocelyn, additional, Finsterbusch, Katja, additional, Tokura, Yoshiki, additional, Souriant, Shanti, additional, Balboa, Luciana, additional, Pingris, Karine, additional, Kviatcowsky, Denise, additional, Raynaud-Messina, Brigitte, additional, Cougoule, Céline, additional, Mercier, Ingrid, additional, Kuroda, Marcelo, additional, González-Montaner, Pablo, additional, Inwentarz, Sandra, additional, Moraña, Eduardo Jose, additional, del Carmen Sasiain, Maria, additional, Neyrolles, Olivier, additional, Maridonneau-Parini, Isabelle, additional, Lugo-Villarino, Geanncarlo, additional, Vérollet, Christel, additional, Herrmann, Alexandra, additional, Thomas, Dominique, additional, Bouzas, Nerea Ferreirós, additional, Lahaye, Xavier, additional, Bhargava, Anvita, additional, Satoh, Takeshi, additional, Gentili, Matteo, additional, Cerboni, Silvia, additional, Silvin, Aymeric, additional, Conrad, Cécile, additional, Ahmed-Belkacem, Hakim, additional, Rodriguez, Elisa C., additional, Guichou, Jean-François, additional, Bosquet, Nathalie, additional, Piel, Matthieu, additional, Le Grand, Roger, additional, King, Megan, additional, Pawlotsky, Jean-Michel, additional, Manel, Nicolas, additional, Hofmann, Henning, additional, Vanwalscappel, Benedicte, additional, Bloch, Nicolin, additional, Landau, Nathaniel, additional, Indik, Stanislav, additional, Hagen, Benedikt, additional, Valle-Casuso, José Carlos, additional, Allouch, Awatef, additional, David, Annie, additional, Barré-Sinoussi, Françoise, additional, Benkirane, Monsef, additional, Pancino, Gianfranco, additional, Saez-Cirion, Asier, additional, Lee, Wing-Yiu, additional, Sloan, Richard, additional, Schulte, Bianca, additional, Blomberg, Jonas, additional, Vargiu, Luana, additional, Rodriguez-Tomé, Patricia, additional, Tramontano, Enzo, additional, Sperber, Göran, additional, Kumari, Namita, additional, Ammosova, Tatiana, additional, Diaz, Sharmeen, additional, Oneal, Patricia, additional, Nekhai, Sergei, additional, Fahrny, Audrey, additional, Gers-Huber, Gustavo, additional, Audigé, Annette, additional, Jayaprakash, Anitha, additional, Sachidanandam, Ravi, additional, Hernandez, Matt, additional, Dillon-White, Marsha, additional, Maze, Emmanuel, additional, Ham, Claire, additional, Almond, Neil, additional, Towers, Greg, additional, Belshaw, Robert, additional, de Sousa-Pereira, Patrícia, additional, Abrantes, Joana, additional, Pizzato, Massimo, additional, Esteves, Pedro J., additional, Kahle, Tanja, additional, Schmitt, Sven, additional, Merkel, Laura, additional, Reuter, Nina, additional, Stamminger, Thomas, additional, Rosa, Ilaria Dalla, additional, Bishop, Kate, additional, Spinazzola, Antonella, additional, Groom, Harriet, additional, Vieyres, Gabrielle, additional, Müsken, Mathias, additional, Zillinger, Thomas, additional, Hornung, Veit, additional, Barchet, Winfried, additional, Häussler, Susanne, additional, Pietschmann, Thomas, additional, Javed, Aneela, additional, Leuchte, Nicole, additional, Salinas, Gabriela, additional, Opitz, Lennart, additional, Sopper, Sieghart, additional, Mummert, Christiane, additional, Hofmann, Christian, additional, Hückelhoven, Angela G., additional, Bergmann, Silke, additional, Müller-Schmucker, Sandra M., additional, Harrer, Ellen G., additional, Dörrie, Jan, additional, Schaft, Niels, additional, Harrer, Thomas, additional, Cardinaux, Laure, additional, Zahno, M.- L., additional, Vogt, H.- R., additional, Zanoni, R., additional, Bertoni, G., additional, Muenchhoff, Maximilian, additional, Goulder, Philip, additional, Keppler, Oliver, additional, Rebensburg, Stephanie, additional, Helfer, Markus, additional, Zhang, Yuwei, additional, Chen, Huicheng, additional, Bernier, Annie, additional, Gosselin, Annie, additional, Routy, Jean- Pierre, additional, Wöhrl, Birgitta, additional, Schneider, Anna, additional, Corona, Angela, additional, Spöring, Imke, additional, Jordan, Mareike, additional, Buchholz, Bernd, additional, Maccioni, Elias, additional, Di Santo, Roberto, additional, Schweimer, Kristian, additional, Schölz, Christian, additional, Weinert, Brian, additional, Wagner, Sebastian, additional, Beli, Petra, additional, Miyake, Yasuyuki, additional, Qi, Jun, additional, Jensen, Lars, additional, Streicher, Werner, additional, McCarthy, Anna, additional, Westwood, Nicholas, additional, Lain, Sonia, additional, Cox, Jürgen, additional, Matthias, Patrick, additional, Mann, Matthias, additional, Bradner, James, additional, Choudhary, Chunaram, additional, Stern, Marcel, additional, Valletta, Elena, additional, Frezza, Caterina, additional, Marino-Merlo, Francesca, additional, Grelli, Sandro, additional, Serafino, Anna Lucia, additional, Mastino, Antonio, additional, Macchi, Beatrice, additional, Kaulfuß, Meike, additional, Windmann, Sonja, additional, Bayer, Wibke, additional, Mikasi, Sello, additional, Heß, Rebecca, additional, Bonsmann, Michael Storcksdieck gen., additional, Kirschning, Carsten, additional, Lepenies, Bernd, additional, Kolenbrander, Anne, additional, Temchura, Vladimir, additional, Iijima, Kenta, additional, Kobayashi, Junya, additional, and Ishizaka, Yukihito, additional

Published
2016
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42. Interplay between HIV-1 replication and RNAi effectors

Author

Benkirane Monsef, Meziane Oussama, Schwartz Olivier, Bennasser Yamina, Emiliani Stéphane, Latreille Daniel, Christine Chable-Bessia, Triboulet Robinson, BMC, Ed., Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Montpellier (UM) - Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS)

Subjects
lcsh:Immunologic diseases. Allergy, Genetics, 0303 health sciences, biology, 030306 microbiology, Non-coding RNA, 3. Good health, 03 medical and health sciences, RNA silencing, Infectious Diseases, Viral replication, RNA interference, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, microRNA, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Gene silencing, Oral Presentation, lcsh:RC581-607, Drosha, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Dicer
Abstract

RNA silencing involving small non coding RNA is a mechanism for gene regulation as well as an innate host cell defence mechanism against viruses. miRNA genes are most often transcribed by RNApolII, and the resulting primary (pri)-miRNA is processed in the nucleus by the RNAse type III Drosha to produce precursor (pre)-miRNA. Pre-miRNAs are then exported to the cytoplasm by Exportin-5 and processed into miRNA/miRNA* (guide/passenger) duplexes through the action of the cytoplasmic type III RNAse Dicer. miRNA/miRNA* is incorporated into the RNA-Induced Silencing Complex (RISC) where miRNA* is degraded, with miRNA serving as a guide for its mRNA target. miRNA-armed RISC targets specific mRNA to inhibit its translation or induce its degradation. Accumulating evidence suggests that the miRNA pathway also controls the replication of both RNA and DNA viruses. We have recently provided evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication and latency. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication in both PBMCs from HIV-1 infected donors and in latently infected cells. Additionally, cellular miRNAs can target HIV-1 mRNA to induce latency. Finally, HIV-1 actively regulates the expression of cellular miRNA which regulate virus replication. We will present further evidence and discuss the involvement of miRNA effectors and cellular miRNA in both activation and repression of HIV-1 replication.

Published
2009

44. Structural and functional studies of HIV-1 pre-integration complexes

Author

Ruff, Marc, primary, Levy, Nicolas, additional, Eiler, Sylvia, additional, Pradeau, Karine, additional, Crucifix, Corinne, additional, Schaetzel, Aurélie, additional, Drillien, Robert, additional, Parissi, Vincent, additional, Emiliani, Stéphane, additional, Mely, Yves, additional, and Schultz, Patrick, additional

Published
2014
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45. Etude de la réactivation de l'expression des provirus HIV-1 latents par la prostratine en synergie avec des inhibiteurs de désacétylases: mécanismes moléculaires impliqués et potentiel thérapeutique

Author

Van Lint, Carine, Pays, Etienne, Marini, Anna Maria, André, Bruno, Lafontaine, Denis, Emiliani, Stéphane, Reuse, Sophie, Van Lint, Carine, Pays, Etienne, Marini, Anna Maria, André, Bruno, Lafontaine, Denis, Emiliani, Stéphane, and Reuse, Sophie

Abstract

L’infection par HIV-1 représente un des problèmes de santé publique majeurs de notre société actuelle. Le traitement HAART (Highly Active AntiRetroviral Therapy) inhibe le cycle réplicatif viral mais ne permet pas l’éradication du HIV-1. La principale cause de cet échec thérapeutique est la persistance de réservoirs cellulaires infectés de manière latente par HIV-1, qui, lors de l’arrêt du traitement HAART, sont à l’origine d’un rebond de la charge plasmatique virale. Le défi actuel est donc de découvrir de nouvelles méthodes d’élimination des cellules réservoirs. Une des stratégies envisagées est de forcer l’expression virale dans les cellules infectées de manière latente afin d’entraîner leur destruction suite à leur détection par le système immunitaire ou suite aux effets cytopathiques viraux. Parallèlement, le traitement HAART serait maintenu afin de limiter la propagation des virions néo-synthétisés. Plusieurs éléments sont impliqués dans la répression transcriptionnelle associée à la latence post-intégrationnelle du virus HIV-1 :la nature du site d’intégration ;l’absence de facteurs cellulaires inductibles tels que NF-κB ;la structure chromatinienne du provirus et les modifications post-traductionnelles des histones ;l’absence de niveaux suffisants de la protéine trans-activatrice Tat. De plus, notre laboratoire a précédemment mis en évidence un lien entre deux de ces éléments, en démontrant, dans une lignée modèle de latence post-intégrationnelle, que la cytokine pro-inflammatoire TNFα, un activateur de la voie de signalisation NF-κB, permet une réactivation synergique de l’expression virale combinée à l’inhibiteur d’histone-désacétylases (HDACI) TSA. Cependant, l’utilisation thérapeutique du TNFα et de la TSA est inenvisageable en raison de leurs toxicités., Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Published
2009

46. Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage

Author

Le Rouzic, Erwann, primary, Bonnard, Damien, additional, Chasset, Sophie, additional, Bruneau, Jean-Michel, additional, Chevreuil, Francis, additional, Le Strat, Frédéric, additional, Nguyen, Juliette, additional, Beauvoir, Roxane, additional, Amadori, Céline, additional, Brias, Julie, additional, Vomscheid, Sophie, additional, Eiler, Sylvia, additional, Lévy, Nicolas, additional, Delelis, Olivier, additional, Deprez, Eric, additional, Saïb, Ali, additional, Zamborlini, Alessia, additional, Emiliani, Stéphane, additional, Ruff, Marc, additional, Ledoussal, Benoit, additional, Moreau, François, additional, and Benarous, Richard, additional

Published
2013
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48. Structural and functional studies of the HIV-1 pre-integration complex

Author

Levy, Nicolas, primary, Eiler, Sylvia, additional, Pradeau-Aubreton, Karine, additional, Crucifix, Corinne, additional, Schaetzel, Aurélie, additional, Drillien, Robert, additional, Parissi, Vincent, additional, Emiliani, Stéphane, additional, Mely, Yves, additional, Schultz, Patrick, additional, and Ruff, Marc, additional

Published
2013
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49. Structural and Functional Role of INI1 and LEDGF in the HIV-1 Preintegration Complex

Author

Maillot, Benoit, primary, Lévy, Nicolas, additional, Eiler, Sylvia, additional, Crucifix, Corinne, additional, Granger, Florence, additional, Richert, Ludovic, additional, Didier, Pascal, additional, Godet, Julien, additional, Pradeau-Aubreton, Karine, additional, Emiliani, Stéphane, additional, Nazabal, Alexis, additional, Lesbats, Paul, additional, Parissi, Vincent, additional, Mely, Yves, additional, Moras, Dino, additional, Schultz, Patrick, additional, and Ruff, Marc, additional

Published
2013
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