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系統識別號 U0026-0812200915253160
論文名稱(中文) 腸病毒七十一型感染的抗體依賴性增強現象
論文名稱(英文) Antibody-dependent enhancement of enterovirus 71 infection
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 97
學期 2
出版年 98
研究生(中文) 陳逸純
研究生(英文) Yi-Chun Chen
電子信箱 s4696101@mail.ncku.edu.tw
學號 s4696101
學位類別 碩士
語文別 中文
論文頁數 67頁
口試委員 指導教授-劉清泉
召集委員-黎煥耀
口試委員-余俊強
口試委員-蘇益仁
中文關鍵字 腸病毒七十一型  細胞激素  腦幹腦炎  動物模式  抗體依賴性增強 
英文關鍵字 brainstem encephalitis  enterovirus 71  antibody-dependent enhancement  animal model  cytokine 
學科別分類
中文摘要 腸病毒七十一型(EV71)是屬於小核醣核酸病毒(Picornaviridae),感染時會出現手足口症、泡疹性咽峽炎等症狀,但在重症患者會併發腦幹腦炎、肺水腫、肺出血及心肺衰竭等症狀。而抗體依賴性增強現象(Antibody-dependent enhancement ,ADE)則已經在多種病毒感染時被報導,且會增強病毒的病徵。為了證明腸病毒感染是否有抗體依賴性增強現象,我們先建立一個體外感染模式,發現THP-1細胞株再配合特定濃度的抗體(IVIG)感染腸病毒七十一型,感染率會比單純只用病毒感染更高,且在抗體依賴性增強的情況下interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-β, tumour necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, IFN-γ inducible protein (IP)-10 和 monokine induced by IFN-γ (MIG)的mRNA表現量會有增加或是延長。因此我們建立一個動物模式,將六天大ICR小鼠腹腔注射稀釋的抗腸病毒七十一型免疫血清或是抗腸病毒七十一型IgG,24小時後感染腸病毒七十一型,發現到在特定稀釋倍率下抗體會引起抗體依賴性增強現象,和只有病毒感染相比,會造成小鼠的臨床症狀加重和死亡率升高,病理切片也可以看到神經和肌肉的損傷更嚴重,而IFN-γ, TNF-α, MCP-1等激素在血清中的含量也較高。初步的結論,我們可以看到EV 71感染時可能會伴隨著抗體依賴性增強的現象,因而造成發炎激素上升,導致發炎反應加劇而使病情更嚴重。
英文摘要 Enterovirus 71 (EV71) belongs to the Human enterovirus A of Picornaviridae. Hand-foot-and-mouth disease and herpangina are the most common clinical features of EV71 infection; however, some patients are complicated with brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, and cardiopulmonary failure. Inflammatory cytokines and chemokines play an important role of EV71 infection. Antibody-dependent enhancement (ADE) infection has been reported in various viruses and has been shown to contribute to disease severity. An in vitro system of EV71 infection through ADE mechanism was established using the human monocytic cell line THP-1. The percentage of EV71-infected cells was significantly enhanced at the concentration (1000-4000 μg/ml) of commercial human immunoglobulin added to THP-1, in comparison with virus-infected cell line without adding commercial human immunoglobulin. EV71 infection was able to enhance the transcription of several inflammatory mediators, including interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-β, tumour necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, IFN-γ inducible protein (IP)-10 and monokine induced by IFN-γ (MIG) via ADE. To further investigate EV71 ADE mechanism in vivo, 6-day-old ICR mice were pretreated with various dilution of anti-EV71 mouse antiserum or anti-EV71 IgG 24 hours before intraperitoneal infection. We found that mice significantly showed aggravated clinical symptoms and increased death at concentration of 1:2-12 of anti-EV71 IgG on the 14 days. Histopathologically, anti-EV71 IgG-added mice also revealed enhanced neuronal and muscular damage than control. Furthermore increased levels of several cytokines and chemokines (IFN-γ, TNF-α, MCP-1) were detected in the sera of anti-EV71 antiserum-added mice. In conclusion, our results demonstrated that the ADE mechanism may involve in the EV71 pathogenesis and contribute to enhance inflammation and tissue damage.
論文目次 中文摘要............................................................................................................ I
英文摘要........................................................................................................... II
誌謝...................................................................................................................IV
目錄....................................................................................................................V
圖目錄..............................................................................................................VII
壹、 緒論
一、 腸病毒七十一型簡介...................................................................1
二、 腸病毒七十一型的流行病學.......................................................3
三、 腸病毒七十一型致病機轉...........................................................4
四、 抗體依賴性增強...........................................................................9
五、 病毒利用抗體依賴性增強來抑制病毒清除機轉.....................10
六、 抗體依賴性增強病毒學研究.....................................................11
貳、 研究動機及目的.................................................................................14
參、 材料和方法
一、 材料
A. 實驗動物.....................................................................................15
B. 細胞株.........................................................................................15
C. 病毒.............................................................................................15
D. 藥品與試劑.................................................................................15
E. 抗體與試劑組.............................................................................16
二、 方法
A. 細胞培養.....................................................................................17
B. 病毒培養與感染.........................................................................19
C. 細胞RNA抽取及PT-PCR, PCR...............................................23
D. 流式細胞儀.................................................................................25
E. 統計方法.....................................................................................26
肆、 結果
一、 腸病毒七十一型感染抗體依賴性增強的In vitro模式...........27
二、 腸病毒七十一型感染抗體依賴性增強的In vivo模式............29
A. 使用抗腸病毒七十一型免疫血清的抗體依賴性增強實驗.....29
B. 使用抗腸病毒七十一型 IgG的抗體依賴性增強實驗............31
伍、 討論
一、 腸病毒七十一型感染抗體依賴性增強模式的建立.................35
二、 腸病毒七十一型感染抗體依賴性增強模式的發炎相關激素變
化................................................................................................36
三、 腸病毒七十一型感染抗體依賴性增強模式的病理變化.........40
四、 腸病毒七十一型抗體依賴性增強和其他已知病毒抗體依賴性
增強比較…................................................................................40
五、 腸病毒七十一型感染抗體依賴性增強現象的流行病學意義.43
陸、 結論.....................................................................................................44
柒、 參考文獻.............................................................................................45
圖…...................................................................................................................52
附圖...................................................................................................................64
作者簡歷...........................................................................................................67
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