单核增生李斯特菌对于宿主抗病毒能力的影响

发布时间：2018-01-17 01:06

本文关键词：单核增生李斯特菌对于宿主抗病毒能力的影响　出处：《中国科学技术大学》2011年硕士论文　论文类型：学位论文

【摘要】：单核细胞增生性李斯特菌(Listeria monocytogenes,54002)是一种胞内病原菌,可以通过食源性方式感染人类,尤其对免疫力低下的群体的健康造成很大的威胁。单增李斯特菌所为一种病原体在微生物学和细胞生物学方面已经有深入的研究。最近以单增李斯特菌为胞内病原菌的免疫学研究亦有较大进展。单增李斯特菌可以通过释放毒力因子溶解素LLO介导参与SUMO化修饰的唯一的E2结合酶Ubc9的降解从而下调宿主细胞整体水平的SUMO化水平,影响细胞的多种生命活动。作为胞内病原菌的代表,人们对单增李斯特菌的分子生物学、细胞生物学以及免疫学方面有了很大的了解。共感染,由于其更接近于人体真实的、复杂的感染事件,是当前感染免疫领域的一个新的重要的研究方向。我们实验室之前的结果表明,参与病毒识别和I型干扰素应答的MDA5分子可以被SUMO化修饰以增强其活性。我们猜测单增李斯特菌感染是否可以通过下调MDA5的SUMO化水平从而干扰宿主的抗病毒应答。正如期望的那样,MDA5分子的SUMO化水平是下调的,但是,出人意料的是,我们发现单增李斯特菌感染可以直接下调MDA5分子的水平。进一步的研究发现,李斯特菌的主要的毒力因子LLO直接介导了这种效应。我们还发现MDA5分子的下调是发生在翻译后水平上的,而不是在转录水平和翻译水平。使用MG132阻断蛋白酶体系统可以阻止MDA5分子的降解过程,这说明LLO介导的MDA5的降解过程是蛋白酶体依赖的。同时我们还发现增强的SUMO化修饰可以提高MDA5的稳定性。由此,我们提出单增李斯特菌的毒力因子LLO可以通过降低MDA5分子的SUMO化修饰水平,从而使泛素可以竞争性的结合到MDA5分子,以一种蛋白酶体依赖的途径发生降解。单增李斯特菌感染导致的MDA5的下调确实影响了宿主细胞的抗病毒I型干扰素应答,增强了病毒在胞内的的复制和感染能力。我们第一次发现单增李斯特菌感染可以直接降解宿主胞内的病毒识别分子MDA5,这使得我们对胞内菌与宿主之间的相互作用有了更深的认识和了解。
[Abstract]:Listeria monocytogenes54002 (Listeria monocytogenes54002) is an endocytic pathogen that can infect humans through food-borne ways. In particular, it poses a great threat to the health of the group with low immunity. Listeria monocytogenes as a pathogen has been studied deeply in microbiology and cell biology. Recently, Listeria monocytogenes is regarded as intracellular disease. Listeria monocytogenes can down-regulate the host by releasing virulent factor LLO to mediate the degradation of Ubc9, the only E2 binding enzyme modified by SUMO. The SUMO level of the whole cell level. As the representative of intracellular pathogenic bacteria, people have a good understanding of the molecular biology, cell biology and immunology of Listeria monocytogenes. Because it is closer to the real and complex infection events in human body, it is a new and important research direction in the field of infectious immunity. MDA5 molecules involved in virus recognition and interferon I response can be modified by SUMO to enhance their activity. We wonder whether Listeria monocytogenes infection can down-regulate the SUMO level of MDA5. To interfere with the host's antivirus response. As expected. The SUMO level of MDA5 molecules is down-regulated, but surprisingly, we found that Listeria monocytogenes infection can directly down-regulate the level of MDA5 molecules. LLO, the main virulence factor of Listeria sp., directly mediates this effect. We also found that the down-regulation of MDA5 molecules occurs at the post-translational level. Using MG132 to block the proteasome system can block the degradation of MDA5 molecules. This indicates that the degradation process of MDA5 mediated by LLO is proteasome dependent. At the same time, we also found that enhanced SUMO modification can improve the stability of MDA5. We propose that the virulence factor LLO of Listeria monocytogenes can reduce the level of SUMO modification of MDA5 molecules so that ubiquitin can be competitively bound to MDA5 molecules. Degradation occurs in a proteasome dependent pathway. The down-regulation of MDA5 caused by Listeria monocytogenes infection does affect the antiviral interferon response of host cells. We found for the first time that Listeria monocytogenes infection can directly degrade the virus recognition molecule MDA5 in host cells. This enables us to have a deeper understanding of the interaction between endomycetes and hosts.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R378

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