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研究生:李佩寰
研究生(外文):Pei-HuanLee
論文名稱:附著於腸病毒71型病毒顆粒上的galectin-1/葡萄糖複合物可增進病毒的感染率與穩定性
論文名稱(外文):Enterovirus 71 virion-associated galectin-1/glucose complex facilitates viral infection and stability
指導教授:蕭璦莉張志鵬張志鵬引用關係
指導教授(外文):Ai-Li ShiauAi-Li Shiau
學位類別:碩士
校院名稱:國立成功大學
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:48
中文關鍵詞:腸病毒71型葡萄糖病毒穩定性凝集素
外文關鍵詞:enterovirus 71galectin-1glucoseviral stabilitylectins
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腸病毒71型屬於無外套膜的正單股核醣核酸病毒,其易感染三歲以下孩童並造成手足口症、腦幹腦炎、癱瘓及肺水腫等神經性症狀。病毒感染的首要步驟是與細胞受體結合而進入細胞,然而在這過程中亦有其他蛋白質可能影響病毒與宿主細胞間的結合。已知Galectins可以藉由結合至多種微生物的表面來幫助免疫系統辨識及反應,在黎煥耀教授實驗室過去研究發現腸病毒71型可與galectin-1及多種醣類結合,而在這個研究中我們進一步發現附著於腸病毒71型上的galectin-1/葡萄糖複合物可增進病毒的感染及穩定性。我們首先證實腸病毒71型表面有galectin-1附著並伴隨病毒感染而結合到細胞表面。相較於一般腸病毒71型,由不表現galectin-1的SK-N-SH細胞培養出來的腸病毒71型對細胞感染力下降,且在小鼠的感染實驗中造成較輕微的症狀。此外,不帶有galectin-1的腸病毒71型較無法承受高溫及長時間保存的處理,而當外補galectin-1時則可增加病毒對環境壓力的抵抗。另一方面,我們也發現感染腸病毒71型的重症小孩血清含高量的galectin-1,顯示galectin-1在臨床上可能參與在腸病毒71型的致病機轉中。此外值得一提的是從無葡萄糖的培養基產出的腸病毒71型降低結合galectin-1及細胞的能力,因此醣類可能影響腸病毒71型和galectin-1的結合。綜合以上結果,附著於腸病毒71型上的galectin-1不僅可幫助病毒感染且增加病毒抵抗溫度及環境中的不穩定性,未來或許可藉由本實驗結果運用於臨床上腸病毒71型感染的診斷或治療。
Enterovirus type 71 (EV71), a non-enveloped RNA virus, causes hand-foot-and-mouth disease (HFMD) and in some cases may progress to severe neurological disease, such as aseptic meningitis, paralysis and neurogenic pulmonary edema in young children. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells. Galectins have been shown to bind glycans on the surface of potentially pathogenic microorganisms and function as recognition and effector factors in innate immunity. Our previous results showed that EV71 can bind to galectin-1 and several carbohydrates. In this study, we further demonstrated that galectin-1/glucose complex on the EV71 virions facilitate viral infection and stability. We found that galectin-1 was associated with the EV71 virions and subsequently bound to SK-N-SH cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenic in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which can be restored following supplement with recombinant galectin-1. Moreover, the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people, indicating that galectin-1 may participate in EV71-induced pathogenesis. Interestingly, EV71 propagated from glucose-free DMEM could not bind galectin-1 and host cells, suggesting that glucose might contribute to the interaction between EV71 and galectin-1. Taken together, our study not only elucidates the roles of galectin-1 and glucose in EV71 infection but also suggests galectin-1 as a therapeutic target for EV71 infection.
中文摘要.............I
英文摘要.............II
誌謝...............III
總目錄..............IV
圖目錄..............VI
縮寫索引.............VII
緒論
一、腸病毒71型病毒學概論..................1
二、腸病毒71型流行病學及臨床症狀..............2
三、腸病毒71型之感染與宿主因子................2
四、凝集素(lectin)和galectin-1..............4
研究目的.......................... 6
材料與方法
實驗材料
一、實驗動物.....................7
二、細胞株......................7
三、病毒株......................7
四、菌種與質體....................7
五、細菌培養液....................8
六、抗體.......................8
七、試劑.......................9
八、塑膠、玻璃製品..................14
九、儀器.......................15

方法
一、 細胞培養.....................17
二、 腸病毒71型小鼠適應株製備............ 17
三、 病毒培養與定量..................18
四、 凝集素結合病毒分析..............18
結果
一、感染腸病毒71型增加細胞膜上galectin-1的表現量...23
二、確認galectin-1附著在腸病毒71型病毒顆粒上.......23
三、附著於腸病毒71型上的galectin-1可以增加病毒的感染力與致病力.. 24
四、附著於腸病毒71型上的galectin-1可增加病毒的耐熱性及穩定性.. 25
五、感染腸病毒71型的病人血清中含高量galectin-1......25
六、葡萄糖可能參與腸病毒71型與galectin-1的結合...26
討論............................27
參考文獻............................32
圖...............................37
作者簡歷............................48

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