Sébastien Legros (2010). La protéine Tax du virus HTLV-1 inhibe la formation des granules de stress en interagissant avec lhistone désacétylase 6 (HDAC6) (thèse de doctorat, en anglais). Université de Liège - Gembloux Agro-Bio Tech, 153 p., 2 tabl., 24 fig. Résumé Le virus T-lymphotrope humain qui infecte 20 millions de personnes dans le monde, est responsable de deux pathologies : une leucémie fatale, appelée leucémie des cellules T de ladulte (ATL) et une maladie neurodégénérative, la paraparésie tropicale spastique (TSP). Loncoprotéine virale Tax-1 constitue une cible thérapeutique privilégiée car elle joue un rôle crucial dans les pathologies induites par HTLV-1. En réponse à un stress comme une infection virale, un stress oxydatif ou une exposition aux UV, la cellule bloque la traduction des ARNm et les séquestre dans des structures cytoplasmiques spécifiques appelées granules de stress (GS). Ces granules sont caractérisés par la présence de protéines spécifiques telles que G3BP et Tiar. Récemment, lhistone désacétylase HDAC6 a été identifiée comme un composant critique de ces GS. Dans ce travail, nous démontrons qu'en présence d'un stress cellulaire, Tax-1 relocalise du noyau vers le cytoplasme. Dans le cytoplasme, Tax-1 colocalise avec G3BP et Tiar dans les GS de certaines cellules. De plus, la protéine Tax-1 exprimée dans le cytoplasme, empêche la formation des GS en interagissant avec HDAC6. Finalement, nous avons montré que les lymphocytes T infectés par HTLV-1 contiennent moins de GS et que ceux-ci sont de taille réduite par rapport aux cellules contrôles Jurkat. Nos résultats révèlent une nouvelle stratégie développée par HTLV-1 et nous postulons que cette nouvelle fonction pourrait avoir un rôle important dans la transformation et loncogenèse induite par le virus HTLV-1. Sébastien Legros (2010). HTLV-1 Tax inhibits stress granules formation by interacting with histone deacetylase 6 (HDAC6) (thèse de doctorat, in English). University of Liège - Gembloux Agro-Bio Tech, 153 p., 2 tabl., 24 fig. Summary Human T cell leukaemia virus type-1 (HTLV-1) which infects 20 million people worldwide is the causative agent of two major diseases: a rapidly fatal leukaemia designated adult T-cell leukaemia (ATL) and a neurological degenerative disease known as tropical spastic paraparesis (TSP). The viral transcriptional activator and oncoprotein Tax-1 has been the major focus of scientific investigation because of its numerous and crucial roles in the pathogenesis of HTLV-1-induced diseases. In response to stress such as viral infection, oxidative stress or UV exposure, the cell blocks mRNA translation and sequesters mRNAs in specific cytoplasmic structures called stress granules (SGs). Stress granules are characterized by the presence of specific proteins such as G3BP and Tiar. Recently, the histone deacetylase HDAC6 was identified as a critical component of SGs. In this report, we demonstrated that in response to cellular stress, Tax-1 relocalizes in the cytoplasm, where it can be found colocalizing with G3BP and Tiar in SGs. Moreover, cytoplasmic Tax-1 prevents SGs formation by interacting with HDAC6. Finally, we have shown that HTLV-1 infected cells exhibit less and smaller SGs than the control Jurkat cells. Our findings thus unravel a new strategy developed by HTLV-1 and we postulate that this new function of Tax might have important role in HTLV-I-induced transformation and oncogenesis. Copyright : Aux termes de la loi belge du 30 juin 1994, sur le droit d'auteur et les droits voisins, seul l'auteur a le droit de reproduire partiellement ou complètement cet ouvrage de quelque façon et forme que ce soit ou d'en autoriser la reproduction partielle ou complète de quelque manière et sous quelque forme que ce soit. Toute photocopie ou reproduction sous autre forme est donc faite en violation de la dite loi et de des modifications ultérieures.

Thesis (Ph.D.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Made available in DSpace on 2014-07-29T15:07:59Z (GMT). No. of bitstreams: 1 Dissertacao Roberta Dias da Silva.pdf: 1341985 bytes, checksum: 7f8563ce1f7b7b1934e5c3dc59b310be (MD5) Previous issue date: 2010-03-02 / The present study evaluated the hematological and biochemical parameters of adult tilapia (Oreochromis niloticus) under the influence of the physiological stress factor in animals submitted to air exposure during fattening in raceway system. Blood cell count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), leukogram, differencial leukocyte count, platelet, glucose, total protein, cholesterol, triglycerides and electrolytes (calcium, chloride, sodium and potassium) were analyzed. The results showed a uniform distribution for red blood cells, hematocrit, hemoglobin, secondary Wintrobe indices, total protein, glucose, cholesterol, and serum ions, indicated by a relatively low variation coefficient. There was positive correlation only for total white blood cells, organic defense cells (neutrophils and lymphocytes), glucose, cholesterol, sodium and calcium. As for the leukocytes (WBC), as the animals were exposed to aeration, the number of leukocytes gradually decreased (leukopenia), simultaneously occurring neutrophilia and lymphopenia. The glycemic index was a good indicator of physiological stress due to hyperglycemia (82.0 + 20.88 mg/dL) demonstrated in the treatments. The air exposure constituted an imbalance factor at the ion homeostasis and at the endogenous cholesterol synthesis. Besides, the recovery time did not result in the complete physiological rehabilitation face the imposed challenge / No presente trabalho avaliaram-se os parâmetros hematológicos e bioquímicos de exemplares adultos de tilápias (Oreochromis niloticus) sob a influência do fator estresse fisiológico em animais submetidos à exposição ao ar durante a engorda em sistema raceway. Foram analisados o eritrograma, teor de hemoglobina, hematócrito, o volume corpuscular médio (VCM), a hemoglobina corpuscular média (HCM), a concentração de hemoglobina corpuscular média (CHCM), o leucograma, contagem diferencial de leucócitos, o plaquetograma, a glicose, a proteína total, o colesterol, o triglicerídeo e os eletrólitos (cálcio, cloretos, sódio e potássio). Os resultados revelaram que houve uma homogeneidade de distribuição para hemácias, hematócrito, hemoglobina, índices hemantimétricos, proteína total, glicose, colesterol, e íons séricos, indicados pelos valores relativamente baixos do coeficiente de variação. Houve correlação positiva somente para leucócitos totais, células de defesa orgânica (neutrófilos e linfócitos), glicose, colesterol, sódio e cálcio. Quanto ao leucograma, à medida que os animais foram expostos ao ar, o número de leucócitos diminuiu gradativamente (leucopenia), ocorrendo simultaneamente neutrofilia e linfopenia. O índice glicêmico constituiu um bom indicador de estresse fisiológico, devido à hiperglicemia (82,0 + 20,88 mg/dL) demonstrada nos tratamentos. A exposição ao ar constituiu um fator de desequilíbrio na homeostase iônica, e na síntese de colesterol endógeno. Entretanto, o tempo de recuperação não ocasionou a completa reabilitação fisiológica frente ao desafio imposto.