本文關(guān)鍵詞：單核增生李斯特菌對于宿主抗病毒能力的影響　出處：《中國科學技術(shù)大學》2011年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 單核細胞增生李斯特菌 SUMO 修飾 Ubc9 MDA-5 病毒

【摘要】：單核細胞增生性李斯特菌(Listeria monocytogenes,54002)是一種胞內(nèi)病原菌,可以通過食源性方式感染人類,尤其對免疫力低下的群體的健康造成很大的威脅。單增李斯特菌所為一種病原體在微生物學和細胞生物學方面已經(jīng)有深入的研究。最近以單增李斯特菌為胞內(nèi)病原菌的免疫學研究亦有較大進展。單增李斯特菌可以通過釋放毒力因子溶解素LLO介導參與SUMO化修飾的唯一的E2結(jié)合酶Ubc9的降解從而下調(diào)宿主細胞整體水平的SUMO化水平,影響細胞的多種生命活動。作為胞內(nèi)病原菌的代表,人們對單增李斯特菌的分子生物學、細胞生物學以及免疫學方面有了很大的了解。共感染,由于其更接近于人體真實的、復雜的感染事件,是當前感染免疫領(lǐng)域的一個新的重要的研究方向。我們實驗室之前的結(jié)果表明,參與病毒識別和I型干擾素應答的MDA5分子可以被SUMO化修飾以增強其活性。我們猜測單增李斯特菌感染是否可以通過下調(diào)MDA5的SUMO化水平從而干擾宿主的抗病毒應答。正如期望的那樣,MDA5分子的SUMO化水平是下調(diào)的,但是,出人意料的是,我們發(fā)現(xiàn)單增李斯特菌感染可以直接下調(diào)MDA5分子的水平。進一步的研究發(fā)現(xiàn),李斯特菌的主要的毒力因子LLO直接介導了這種效應。我們還發(fā)現(xiàn)MDA5分子的下調(diào)是發(fā)生在翻譯后水平上的,而不是在轉(zhuǎn)錄水平和翻譯水平。使用MG132阻斷蛋白酶體系統(tǒng)可以阻止MDA5分子的降解過程,這說明LLO介導的MDA5的降解過程是蛋白酶體依賴的。同時我們還發(fā)現(xiàn)增強的SUMO化修飾可以提高MDA5的穩(wěn)定性。由此,我們提出單增李斯特菌的毒力因子LLO可以通過降低MDA5分子的SUMO化修飾水平,從而使泛素可以競爭性的結(jié)合到MDA5分子,以一種蛋白酶體依賴的途徑發(fā)生降解。單增李斯特菌感染導致的MDA5的下調(diào)確實影響了宿主細胞的抗病毒I型干擾素應答,增強了病毒在胞內(nèi)的的復制和感染能力。我們第一次發(fā)現(xiàn)單增李斯特菌感染可以直接降解宿主胞內(nèi)的病毒識別分子MDA5,這使得我們對胞內(nèi)菌與宿主之間的相互作用有了更深的認識和了解。
[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.
【學位授予單位】：中國科學技術(shù)大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R378

【相似文獻】

相關(guān)期刊論文 前10條

1 田霞;李遠釗;張培正;朱英蓮;;即食菜卷和肉湯中單增李斯特菌生長模型及控制研究[J];食品與發(fā)酵工業(yè);2005年10期

2 趙貴明,何艷玲,邊凌淳,劉沛;李斯特氏菌選擇性培養(yǎng)基改良實驗[J];中國公共衛(wèi)生;2004年08期

3 王璐璐;侯廣玉;楊玉英;;單核細胞增生性李斯特菌mpl基因的克隆及其原核表達載體的構(gòu)建[J];黑龍江八一農(nóng)墾大學學報;2011年01期

4 吳瑞英;黃寶明;梁均和;;單增李斯特菌選擇性增菌培養(yǎng)分離的初步探討[J];中國衛(wèi)生檢驗雜志;2007年05期

5 張U，

本文編號：1435608