Protection against Retrovirus Pathogenesis by SR Protein Inhibitors
| Autor: | Marc Plays, David S. Grierson, Marc Sitbon, Jamal Tazi, Anne Keriel, Florence Mahuteau-Betzer, Chantal Jacquet |
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| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Faculty of Pharmaceutical Sciences, University of British Columbia (UBC), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Conception, synthèse et vectorisation de biomolécules. ( CSVB ), Université Paris Descartes - Paris 5 ( UPD5 ) -INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), University of British Columbia ( UBC ), Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5) |
| Rok vydání: | 2009 |
| Předmět: |
Indoles
RNA Splicing viruses lcsh:Medicine RNA-binding protein Molecular Biology/RNA Splicing Biology Mice 03 medical and health sciences SR protein Retrovirus Chemical Biology Infectious Diseases/Viral Infections Murine leukemia virus Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Nuclear protein lcsh:Science [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology Cell Biology/Gene Expression 030304 developmental biology 0303 health sciences Messenger RNA Multidisciplinary Serine-Arginine Splicing Factors lcsh:R 030302 biochemistry & molecular biology Nuclear Proteins RNA-Binding Proteins biology.organism_classification Virology 3. Good health Leukemia Virus Murine Chemical Biology/Small Molecule Chemistry Infectious Diseases Retroviridae Animals Newborn Viral replication RNA splicing lcsh:Q Leukemia Erythroblastic Acute Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2009, 4 (2), pp.e4533. ⟨10.1371/journal.pone.0004533⟩ PLoS ONE, Public Library of Science, 2009, 4 (2), pp.e4533. 〈10.1371/journal.pone.0004533〉 PLoS ONE, Vol 4, Iss 2, p e4533 (2009) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0004533 |
| Popis: | International audience; Indole derivatives compounds (IDC) are a new class of splicing inhibitors that have a selective action on exonic splicing enhancers (ESE)-dependent activity of individual serine-arginine-rich (SR) proteins. Some of these molecules have been shown to compromise assembly of HIV infectious particles in cell cultures by interfering with the activity of the SR protein SF2/ASF and by subsequently suppressing production of splicing-dependent retroviral accessory proteins. For all replication-competent retroviruses, a limiting requirement for infection and pathogenesis is the expression of the envelope glycoprotein which strictly depends on the host splicing machinery. Here, we have evaluated the efficiency of IDC on an animal model of retroviral pathogenesis using a fully replication-competent retrovirus. In this model, all newborn mice infected with a fully replicative murine leukemia virus (MLV) develop erythroleukemia within 6 to 8 weeks of age. We tested several IDC for their ability to interfere ex vivo with MLV splicing and virus spreading as well as for their protective effect in vivo. We show here that two of these IDC, IDC13 and IDC78, selectively altered splicing-dependent production of the retroviral envelope gene, thus inhibiting early viral replication in vivo, sufficiently to protect mice from MLV-induced pathogenesis. The apparent specificity and clinical safety observed here for both IDC13 and IDC78 strongly support further assessment of inhibitors of SR protein splicing factors as a new class of antiretroviral therapeutic agents. |
| Databáze: | OpenAIRE |
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