本文關(guān)鍵詞：單核增生李斯特菌對(duì)于宿主抗病毒能力的影響　出處：《中國(guó)科學(xué)技術(shù)大學(xué)》2011年碩士論文　論文類(lèi)型：學(xué)位論文

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【摘要】：單核細(xì)胞增生性李斯特菌(Listeria monocytogenes,54002)是一種胞內(nèi)病原菌,可以通過(guò)食源性方式感染人類(lèi),尤其對(duì)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(xué)和細(xì)胞生物學(xué)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(xué)研究亦有較大進(jìn)展。單增李斯特菌可以通過(guò)釋放毒力因子溶解素LLO介導(dǎo)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(xì)胞整體水平的SUMO化水平,影響細(xì)胞的多種生命活動(dòng)。作為胞內(nèi)病原菌的代表,人們對(duì)單增李斯特菌的分子生物學(xué)、細(xì)胞生物學(xué)以及免疫學(xué)方面有了很大的了解。共感染,由于其更接近于人體真實(shí)的、復(fù)雜的感染事件,是當(dāng)前感染免疫領(lǐng)域的一個(gè)新的重要的研究方向。我們實(shí)驗(yàn)室之前的結(jié)果表明,參與病毒識(shí)別和I型干擾素應(yīng)答的MDA5分子可以被SUMO化修飾以增強(qiáng)其活性。我們猜測(cè)單增李斯特菌感染是否可以通過(guò)下調(diào)MDA5的SUMO化水平從而干擾宿主的抗病毒應(yīng)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(jìn)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(dǎo)了這種效應(yīng)。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(guò)程,這說(shuō)明LLO介導(dǎo)的MDA5的降解過(guò)程是蛋白酶體依賴的。同時(shí)我們還發(fā)現(xiàn)增強(qiáng)的SUMO化修飾可以提高M(jìn)DA5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(guò)降低MDA5分子的SUMO化修飾水平,從而使泛素可以競(jìng)爭(zhēng)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(dǎo)致的MDA5的下調(diào)確實(shí)影響了宿主細(xì)胞的抗病毒I型干擾素應(yīng)答,增強(qiáng)了病毒在胞內(nèi)的的復(fù)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(shí)別分子MDA5,這使得我們對(duì)胞內(nèi)菌與宿主之間的相互作用有了更深的認(rèn)識(shí)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(xué)位授予單位】：中國(guó)科學(xué)技術(shù)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類(lèi)號(hào)】：R378

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