埃博拉病毒糖蛋白的毒性研究

发布时间：2018-03-02 19:17

本文选题：埃博拉病毒　切入点：糖蛋白　出处：《北京协和医学院》2011年硕士论文　论文类型：学位论文

【摘要】：埃博拉病毒是一种丝状病毒科单股负链无节段的RNA病毒。该病毒可导致埃博拉出血热,多表现为高热、休克及出血倾向。在疾病发展过程中,埃博拉病毒可损害血管内皮,进而导致血管通透性增加。目前己确定埃博拉病毒的毒性主要源自其表面的糖蛋白(GP)。内源性表达该蛋白可以导致血管内皮细胞失去粘附能力而脱落、漂浮,从而损害血管的完整性。本室建立了外源性携带Fc标签的糖蛋白GP1亚基(GP1-Fc)导致血管内皮细胞漂浮的模型。为进一步明确该模型中GP1-Fc毒性相关的结构域,本研究构建并表达、纯化了GP1相关的系列蛋白。同时发现了外源性添加的GP1-Fc蛋白以多聚体的形式存在,可能存在模拟天然GP分子构象的情况。此外,本研究还证实了在293T细胞中内源性表达GP不会直接导致细胞死亡。
[Abstract]:Ebola virus is a single-stranded and segmented RNA virus in the family filamentae. The virus can cause Ebola haemorrhagic fever, which is characterized by high fever, shock and haemorrhage tendency. During the development of the disease, Ebola virus can damage the vascular endothelium. This leads to increased vascular permeability. It has been determined that the toxicity of Ebola virus is mainly due to the glycoprotein GPN on its surface. Endogenous expression of this protein can cause vascular endothelial cells to lose adhesion and fall off and float. In order to further clarify the domain associated with GP1-Fc toxicity, we constructed and expressed a model of exogenous glycoprotein GP1 subunit GP1-Fc, which was used to induce vascular endothelial cells to float. A series of proteins related to GP1 were purified. It was also found that exogenous GP1-Fc proteins existed in the form of polymers, which might mimic the conformation of natural GP molecules. This study also confirmed that endogenous expression of GP in 293T cells did not directly lead to cell death.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R373

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