首页> 外文OA文献 >La glycoprotéine de fusion F des paramyxovirus : étude structure-fonction et ingénierie de F en vue du développement d'applications thérapeutiques
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La glycoprotéine de fusion F des paramyxovirus : étude structure-fonction et ingénierie de F en vue du développement d'applications thérapeutiques

机译:副粘病毒融合糖蛋白F:F的结构功能研究和工程化,以开发治疗应用

摘要

Human respiratory paramyxoviruses are responsible for infectious diseases and hospitalisations among infants, children, elderly and the immunocompromised. These viruses harbour two glycoproteins implicated in virus entry into the cell. The attachment glycoprotein (HN,G or H) is implicated the virus attachment on a target cell receptor, and HN is also suspected to activate the second glycoprotein, the fusion protein (F). This latter glycoprotein can perform the fusion between the cellular membrane and the viral envelope. The mechanism of activation of the F protein, is not well-defined, even with the structural characterisation for some viruses studied inthis thesis. This thesis work is focussed on the viral glycoprotein of parainfluenza virus type 2 (hPIV-2), parainfluenza virus type 5 (PIV-5), and the fusion glycoprotein of human Metapneumovirus (hMPV).The first part of this project was the characterization of a mutation observed in the F protein natural variants of hPIV-2. This work highlights the importance of the F2 subunit of F in the fusion regulation. A second part of the project consisted of the study of the mechanism of F hMPV entry into the cell, induced by F glycoprotein. This work showed that it was possible to dissociate the characteristics of the F glycoprotein, in order to allow a better understanding of these characteristics. This engineering work on the F protein was used to understand the basic science but could also be used in the development of therapeutic tools.The therapeutic use of F PIV-5 was also evaluated in an oncolytic vector based on adenovirus type 5 (AdV-5). Its expression in tumours showed a highly cytotoxic activity for the target cells in vivo, but also in vitro on immunocompetent rodents.
机译:人呼吸副粘病毒负责婴儿,儿童,老年人和免疫力低下的传染病和住院治疗。这些病毒带有两种糖蛋白,与病毒进入细胞有关。附着糖蛋白(HN,G或H)与病毒附着在靶细胞受体上有关,还怀疑HN激活了第二种糖蛋白,即融合蛋白(F)。后者的糖蛋白可以执行细胞膜和病毒包膜之间的融合。即使对本文研究的某些病毒进行结构表征,F蛋白的激活机制仍未明确。本论文的研究重点是副流感病毒2型(hPIV-2),副流感病毒5型(PIV-5)和人间质肺病毒(hMPV)融合糖蛋白的病毒糖蛋白。本项目的第一部分是表征在hPIV-2的F蛋白天然变体中观察到的突变。这项工作强调了F的F2亚基在融合调控中的重要性。该项目的第二部分包括对F hMPV由F糖蛋白诱导进入细胞的机制的研究。这项工作表明,可以解离F糖蛋白的特征,以便更好地理解这些特征。 F蛋白的这项工程工作被用于了解基础科学,但也可用于治疗工具的开发。还基于5型腺病毒(AdV-5)在溶瘤载体中评估了F PIV-5的治疗用途)。它在肿瘤中的表达在体内显示了对靶细胞的高度细胞毒性活性,而且在体外对具有免疫能力的啮齿动物也具有很高的细胞毒活性。

著录项

  • 作者

    Le Bayon Jean-Christophe;

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  • 年度 2013
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  • 原文格式 PDF
  • 正文语种 fr
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