臺灣博碩士論文加值系統

兔病毒性出血症 (Rabbit haemorrhagic disease；RHD) 為急性的兔隻病毒性疾病，因成兔感染兔病毒性出血症病毒 (Rabbit haemorrhagic disease virus；RHDV) 所引起。此疾病之特徵為傳染性高，可藉由直接和間接傳染途徑迅速散播病原，與高死亡率 (80-100%)。台灣病例於1994年由呂榮修博士首先發現，之後陸續仍有零星疫情發生。本研究收集自1994至2002年間台灣地區七個RHDV分離株，分別進行病毒增殖後，以氯化銫 (CsCl) 梯度離心純化病毒並萃取其核酸，採用RT-PCR增幅capsid protein (VP60) 核酸片段約1.74 kb，經由此片段的核酸定序與分析結果，台灣RHDV分離株的核酸序列有92.5-99.8 %的相似性，且分離株之間可分為兩個主要族群，這兩族群在演化分析上皆與德國分離株極為接近。RHD已存在台灣近十年時間，為了尋找那一RHDV分離株，可提供最好的免疫能力，保護兔群免於其他分離株的攻擊，所以先將不同的分離株，製作成十倍肝臟乳劑，離心後收取上清液，加入福馬林完成不活化臟器疫苗之製作。首先，進行各株不活化臟器疫苗的免疫試驗，並經由血球凝集抑制試驗、酵素結合免疫吸附分析法和西方轉漬法測試免疫後3週內之抗體反應；結果顯示，各個RHDV分離株的不活化臟器疫苗，所提供的免疫能力相似，且免疫的兔隻並無死亡的情形。進一步再以1994、2002年兩株RHDV的不活化臟器疫苗，進行交叉保護試驗，並以同樣方法檢測免疫與攻毒後的抗體爬升；結果顯示，此兩個分離株之間具有交叉保護能力。經由這一連串的實驗，我們得到的結論，自1994至2002年台灣地區的RHDV分離株，可分為兩個族群，各分離株核酸序列有0.2-7.5 % 差異性，而且不同的分離株製成的不活化臟器疫苗，能提供相似的保護能力，免於相同或相異毒株的感染，所以在台灣，不論施打那一分離株所製得的疫苗，在田間仍是預防此疾病可行之措施。

中文摘要.....................................................Ⅰ
Abstract.....................................................Ⅱ
目次.........................................................Ⅲ表次.........................................................Ⅳ
圖次.........................................................Ⅴ
第一章 緒言................................................1
第二章 文獻探討............................................2
第一節 歷史背景............................................2
第二節 病毒的分類..........................................2
2-2.1 RHDV的歸屬..........................................3
2-2.2 無致病性 (nonpathogenic) 分離株的出現...............3
第三節 病毒的特色..........................................4
2-3.1 病毒的形態..........................................4
2-3.2 基因體結構..........................................4
2-3.3 生物學特性..........................................6
2-3.4 培養及增殖特性......................................6
2-3.5 親和細胞............................................7
2-5.6 病毒耐受性..........................................8
第四節 致病機轉............................................8
第五節 流行病學............................................9
第六節 傳染途徑............................................9
第七節 疾病特徵...........................................10
2-7.1 臨床症狀...........................................10
2-7.2 病理變化….........................................11
2-7.3 組織病理學病變.....................................11
第八節 診斷方法...........................................12
第九節 治療及預防.........................................13
2-9.1 治療與處置.........................................13
2-9.2 臟器不活化疫苗的施行...............................13
2-9.3 接種時機...........................................14
2-9.3 疫苗的未來展望.....................................14
第三章 材料與方法.........................................15
第一節 病毒之選擇、增殖與純化及其力價之檢測...............15
3-1.1 病毒株之選擇.......................................15
3-1.2 實驗動物…………….................................15
3-1.3 野外病毒分離及增殖.................................15
3-1.4 病毒之力價.........................................15
3-1.5 病毒之純化.........................................16
3-1.6 病毒之確定.........................................16
第二節 病毒之序列分析.....................................17
3-2.1 病毒核酸之萃取.....................................17
3-2.2 反轉錄聚合酵素連鎖反應之初步確定...................18
3-2.3 使用引子設計.......................................18
3-2.4 反轉錄聚合酵素連鎖反應 (RT-PCR) ...................18
3-2.5 RT-PCR產物之偵測...................................19
3-2.6 純化RT-PCR產物.....................................19
3-2.7 定序RT-PCR產物.....................................20
3-2.8 核酸序列之分析...................................20
3-2.9 胺基酸序列比對及親緣樹分析.........................21
第三節 不活化疫苗之製作...................................21
3-3.1 不活化病毒株之選擇.................................21
3-3.2 病毒之不活化.......................................21
3-3.3 雜菌檢測與不活化病毒之確定.........................21
3-3.4 不活化疫苗之劑量...................................22
3-3.5 高度免疫血清之製備.................................22
第四節 免疫試驗...........................................22
3-4.1 免疫計劃...........................................22
3-4.2 攻毒試驗...........................................23
第五節 交叉保護能力試驗...................................23
3-5.1 交叉保護病毒株之選擇...............................23
3-5.2 免疫計劃...........................................23
3-5.3 交叉攻毒試驗.......................................23
第六節 免疫及交叉保護試驗之抗體力價測定...................24
3-6.1 血球凝集抑制試驗 (HIT) ............................24
3-6.2 酵素結合免疫吸附分析法 (ELISA ) ...................25
3-6.3 西方轉漬法 (Multi-screen channel) .................25
第四章 結果...............................................26
第一節 病毒之純化及力價確定...............................26
4-1.1 病毒之力價分析.....................................26
4-1.2 病毒純化...........................................26
4-1.3 病毒之確定結果.....................................26
第二節 病毒之序列分析結果.................................27
4-2.1 病毒核酸之萃取確認...............................27
4-2.2 RT-PCR產物之確認...................................27
4-2.3 VP60基因定序與親緣樹圖結果分析.....................27
4-2.4 VP60的胺基酸序列比對及親緣樹分析...................28
第三節 不活化疫苗之製作結果...............................29
4-3.1 雜菌檢測與不活化病毒之確定.........................29
4-3.2 不活化疫苗之劑量...................................29
第四節 免疫試驗之抗體反應.................................29
4-4.1 以HI檢測抗體反應...................................29
4-4.2 以ELISA分析抗體反應................................30
4-4.3 以西方轉漬法 (Multi-screen channel) 分析抗體反應...30
4-4.4 免疫試驗保護能力之確定.............................30
第五節 交叉保護能力試驗抗體反應...........................31
4-5.1 以HI檢測抗體反應...................................31
4-5.2 以ELISA分析抗體反應................................31
4-5.3 以西方轉漬法 (Multi-screen channel) 分析抗體反應...31
4-5.4 交叉保護能力試驗之結果.............................32
第五章 討論...............................................53
參考文獻 ...................................................58
附錄一 比對台灣RHDV分離株之VP60基因核酸序列之差異.......71
附錄二 比對台灣RHDV分離株之VP60基因胺基酸序列之差異.......74
附錄三 台灣與世界其他地區RHDV分離株之VP60基因核酸序列之差
異.................................................75
附錄四 台灣與世界其他地區RHDV分離株之VP60基因胺基酸序列之差
異.................................................85

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