PMID: identifiant de la référence Pubmed : |
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(22458338)  |
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| titre : |
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Host-pathogen interactome mapping for HTLV-1 and 2 retroviruses. |
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| auteur(s) : |
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Nicolas Simonis1, 2, 3, Jean-François Rual1, 2, Irma Lemmens4, Mathieu Boxus5, Tomoko Hirozane-Kishikawa1, 2, Jean-Stéphane Gatot6, Amélie Dricot1, 2, Tong Hao1, 2, Didier Vertommen7, Sébastien Legros5, Sarah Daakour5, Niels Klitgord1, 2, Maud Martin5, Jean-François Willaert5, Franck Dequiedt5, Vincent Navratil8, Michael Cusick1, 2, Arsène Burny5, Carine Van Lint6, David Hill1, 2, Jan Tavernier4, Richard Kettmann5, Marc Vidal ( ) 1, 2, Jean-Claude Twizere ( ) 1, 5 |
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| laboratoire : |
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| 1 : |
CCSB - Center for Cancer Systems Biology |
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| http://ccsb.dfci.harvard.edu/web/www/ccsb/ |
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| Dana-Farber Cancer Institute – Department of Cancer Biology |
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| 450 Brookline Ave., Boston, MA 02215 |
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| États-Unis |
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| 2 : |
Department of Genetics [Boston] |
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| http://genetics.med.harvard.edu/ |
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| Harvard Medical School |
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| 77 Avenue Louis Pasteur, Boston, MA 02115 |
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| États-Unis |
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| 3 : |
BiGRe - Laboratoire de Bioinformatique des Génomes et des Réseaux |
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| http://www.scmbb.ulb.ac.be/ |
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| Université Libre de Bruxelles |
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| Université Libre de Bruxelles, CP263 Boulevard du Triomphe, Campus Plaine. B-1050 Bruxelles, Belgium |
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| Belgique |
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| 4 : |
Department of Medical Protein Research |
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| VIB – Ghent University |
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| B-9000 Ghent |
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| Belgique |
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| 5 : |
Protein Signaling and Interactions - GIGA Research Center |
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| University of Liège – Department of Chemistry - Gembloux ABT |
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| 1 avenue de l'Hôpital, 4000 Liege |
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| Belgique |
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| 6 : |
Laboratory of Molecular Virology |
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| Institut de Biologie et de Médecine Moléculaires – Université Libre de Bruxelles |
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| 12 Rue des Profs Jeener et Brachet, 6041 Gosselies |
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| Belgique |
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| 7 : |
Hormones and Metabolism Unit |
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| Université Catholique de Louvain (UCL) - Belgique – Duve Institute |
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| 75 Avenue Hippocrate, 1200 Brussels |
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| Belgique |
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| 8 : |
Ecole Nationale Vétérinaire de Lyon |
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| Université de Lyon – Institut national de la recherche agronomique (INRA) : UMR754 – INSERM : U851 |
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| 21 avenue Tony Garnier, Lyon F-69007 |
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| France |
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| résumé : |
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ABSTRACT: BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression. RESULTS: We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway. CONCLUSIONS: This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and 2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection. |
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| domaine : |
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Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses
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langue du texte intégral : |
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Anglais |
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| ISSN : |
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1742-4690 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1186/1742-4690-9-26 |
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| journal : |
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| Audience : |
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internationale |
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| date de publication : |
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29/03/2012 |
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date de publication électronique : |
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29/03/2012 |
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| volume : |
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9 |
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| numéro : |
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1 |
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| page, identifiant, ... : |
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26 |
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| mots-clés auteur : |
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HTLV – Interactome – Retrovirus – ORFeome – Tax – HBZ |
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| contrat, financement : |
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This work was supported by US National Human Genome Research Institute grants 2R01HG001715 (to M.V. and D.E.H.) and 5P50HG004233 (to M.V.), US National Cancer Institute grant 5U54CA112952 (to J. Nevins, subcontract to M.V.), the Ellison Foundation (to M.V.), DFCI Institute Sponsored Research funds (to M.V.), FRS-FNRS grants 7.4.594.07 and 7.4.545.08 (to R.K. and J.-C.T.) and Interuniversity Attraction Poles Program- Belgian Science Policy (IUAP-BELSPO PVI/28 to F.D. and J.T.). |
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