Human T-cell lymphotropic virus type 1 (HTLV-1) infects about 20 million individuals worldwide. This retrovirus induces two major types of pathologies: adult T-cell leukemia (ATL) or a neurodegenerative disorder called HAM/TSP (HTLV-associated myelopathy/tropical spastic paraparesis). The HTLV-1 transactivator protein (Tax) plays a central role in the development of these pathologies. We hypothesized that Tax activities are modulated through complexation with cellular proteins. Using the yeast two-hybrid method, we isolated two cellular Tax binding proteins, Gβ2 and MCM3, involved in cell signaling and DNA replication, respectively. We demonstrate that the interplay between Tax and Gβ2 modulates migration of infected T-lymphocytes toward chemokines. On the other hand, by interacting with MCM3, Tax accelerates DNA replication during the synthesis phase of the cell cycle and generates DNA damages responsible for cell transformation. We have thus identified two novel Tax partners potentially participating to the mechanisms by which the viral protein ensures viral persistence and leads to the development of HTLV-1 pathologies.
| Identifer | oai:union.ndltd.org:BICfB/oai:ETDFUSAGx:FUSAGxetd-04232008-104539 |
| Date | 26 May 2008 |
| Creators | Boxus, Mathieu |
| Contributors | Portetelle, Daniel, Bex, CERIA - ULB, Vanderplasschen, ULg, Lognay, Georges, Willems, Luc, Kettmann, Richard, Théwis, André |
| Publisher | Universite de Gembloux |
| Source Sets | Bibliothèque interuniversitaire de la Communauté française de Belgique |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://bictel-fusagx.ulg.ac.be/ETD-db/collection/available/FUSAGxetd-04232008-104539/ |
| Rights | restricted, Je certifie avoir complété et signé le contrat BICTEL/e remis par le gestionnaire facultaire. |
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