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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 陳培哲(Pei-Jer Chen) | |
dc.contributor.author | Guan-Lin Chen | en |
dc.contributor.author | 陳冠霖 | zh_TW |
dc.date.accessioned | 2021-06-17T02:37:16Z | - |
dc.date.available | 2019-09-08 | |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-17 | |
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Ceccherini-Nelli and B. Matteoli, Editors. 2012, InTech: Rijeka. p. Ch. 01. 53. Okuyama-Dobashi, K., et al., Hepatitis B virus efficiently infects non-adherent hepatoma cells via human sodium taurocholate cotransporting polypeptide. Scientific Reports, 2015. 5: p. 17047. 54. Hsieh, S.Y., et al., Hepatitis delta virus genome replication: a polyadenylated mRNA for delta antigen. J Virol, 1990. 64(7): p. 3192-8. 55. Modahl, L.E. and M.M. Lai, The large delta antigen of hepatitis delta virus potently inhibits genomic but not antigenomic RNA synthesis: a mechanism enabling initiation of viral replication. J Virol, 2000. 74(16): p. 7375-80. 56. Sureau, C., et al., Cloned hepatitis delta virus cDNA is infectious in the chimpanzee. Journal of Virology, 1989. 63(10): p. 4292-4297. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68825 | - |
dc.description.abstract | D型肝炎病毒(HDV)是在所有動物病毒中唯一已知的單股環狀RNA病毒,在自然界中通常伴隨著B型肝炎病毒(HBV)共同感染,因此HDV是在1970年代的B型肝炎病毒(HBV)感染患者體內首次被發現。HDV的感染需要HBV表面外套膜蛋白幫助HDV包裹形成完整具感染性的病毒顆粒,所以HDV不能在沒有HBV的共同感染下完成其生命週期。一旦進入宿主細胞,HDV便會開始複製,與有編碼其自身聚合酶的HBV不同,HDV的複製需要來自宿主酵素的參與。在HDV複製過程中,第一步可能是經由宿主RNA聚合酶II(RNA pol II)以HDV genomic RNA做為模板產生HDV mRNA, mRNA轉譯後所做出的S-HDAg會被送入細胞核以幫助HDV的複製。其他種類的HDV RNA,例如antigenomic RNA,首先會在核仁中以genomic RNA為模板進行合成,之後antigenomic RNA會被送入核質中並做為合成genomic RNA的模板。雖然genomic RNA以及mRNA的合成皆有RNA pol II的參與。然而,antigenomic RNA的合成是否同樣藉由RNA pol II仍然是有爭議的,因為加入RNA pol II抑制劑α-amanitin並不能有效阻斷該過程。為了研究參與HDV複製的細胞酵素,我們希望在過表達HBV受體(人類鈉離子牛磺膽酸共轉運蛋白)的肝癌細胞系HepG2-NTCP-C4上建立穩定的HDV感染系統,以模擬HDV在自然條件下的感染週期而不是在以往發表的實驗中所使用的轉染系統。為了使其成為穩定的實驗模式,HDV的感染率必須達到一定水平(至少要達到30%),但這仍然是我們所面臨的重大難關。雖然經過許多不同的方法嘗試增加感染效率,但HDV在 HepG2-NTCP-C4感染率仍然只有5-10%左右,我們正在試著找出造成HDV低感染率的原因並嘗試提升感染效率,希望在未來透過我們實驗團隊的努力,能將此實驗模型發展成為研究HDV複製的利器。 | zh_TW |
dc.description.abstract | Hepatitis D virus (HDV) was first discovered in the 1970s from patients already infected with hepatitis B virus (HBV). To date, HDV is the only known single circular RNA virus that infects animals. Being the satellite virus of HBV, HDV requires HBV surface protein to help HDV virion assembly. In other words, without the help of HBV, HDV would not be able to complete its life cycle. HDV replication starts once the virion enters the host cells. Unlike HBV, which encodes its own polymerase, HDV requires cellular enzymes from host to take part in its replication cycle. The first step of replication is to generate HDV S-HDAg mRNA from HDV genomic RNA; such step is mediated by host DNA dependent RNA polymerase II (RNA pol II). After the translation of HDV S-HDAg mRNA, the S-HDAg protein product will be sent to the nucleus to assist HDV replication. Other RNA species, such as antigenomic RNA, will be synthesized in nucleolus from genomic RNA and then get sent to nucleoplasm for genomic RNA synthesis. Previous literature suggests that RNA Pol II may involve in the syntheses of HDV genomic RNA and mRNA. However, whether RNA pol II also plays a role in the synthesis of antigenomic RNA remains controversial as evidence showed that the RNA pol II inhibitor, α-amanitin, was unable to block such process. To investigate which cellular enzymes that may participate in HDV replication, this study aims to generate a stable infection system based on the HepG2-NTCP-C4 hepatoma cell line that is overexpressed with the HBV entry receptor, human Sodium taurocholate cotransporting polypeptide (NTCP). Instead of using the transfection system in the past, this new approach is able to more closely mimic natural infection condition of HDV. In order to optimize the infection system, the HDV infection rate has to reach a certain level—at least 30%—to become a more mature tool, yet this remains a major challenge to the current study. So far, the data suggested that the infection efficiency in this study remained at a low level (around 5-10%). Due to the lack of appropriate tools, the study of HDV has been greatly hindered throughout the years. With continuous efforts of our team, the causes of such low infection rate may be identified in the near future. By then, armed with the improved research model, our team may be able to reveal the many mysteries that lay in the field of HDV. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T02:37:16Z (GMT). No. of bitstreams: 1 ntu-106-R04445118-1.pdf: 2144537 bytes, checksum: 6f506c83ce87e8c682b5d6f2db040b8d (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 口試委員會審定書 I
誌謝 II 中文摘要 III Abstract V 第一章 序論 1 1.1. D型肝炎病毒歷史 1 1.2. D型肝炎病毒簡介 2 1.3. D型肝炎病毒生命週期 2 1.4. D型肝炎病毒 RNA 4 (1) 基因體RNA (G-RNA) 5 (2) 反基因體RNA (AG-RNA) 5 (3) mRNA 6 1.5. D型肝炎病毒δ抗原 6 (1) 小型δ抗原(S-HDAg) 6 (2) 大型δ抗原(L-HDAg) 7 1.6. 人類鈉離子牛磺膽酸共轉運蛋白過表達的肝癌細胞系 7 1.7. 自噬作用及巴伐洛霉素A1( bafilomycin A1) 8 1.8. 病毒及自噬作用間的交互作用 9 1.9. 實驗假說 10 第二章 材料與方法 11 2.1. 細胞培養 11 2.2. 質體構造 12 (1) pS1x 12 (2) pCD2G 和pCD2AG 12 (3) D1T 12 2.3. 製備D型肝炎病毒 13 (1) 病毒顆粒的製備與定量 13 (2) 濃縮病毒粒子 14 (3) 體外轉錄作用(IVT) 15 2.4. D型肝炎病毒的感染 15 (1) 貼壁感染 15 (2) 懸浮感染 16 2.5. 檢測D型肝炎病毒感染的結果 17 (1) 免疫螢光染色法 17 (2) 西方墨點法 17 (3) 南方墨點法 19 第三章 實驗結果 20 3.1. 定量D型肝炎病毒粒子並確認病毒粒子中HBsAg和HDAg的表現 20 3.2. D型肝炎病毒在HepG2-hNTCP-C4細胞系的感染結果 21 3.3. 皮質醇對於D型肝炎病毒感染HepG2-hNTCP-C4細胞系的影響 22 3.4. 巴伐洛霉素A1對於D型肝炎病毒感染HepG2-hNTCP-C4細胞系的影響 23 3.5. 懸浮感染對於D型肝炎病毒感染HepG2-hNTCP-C4細胞系的影響 24 第四章 討論 26 第五章 結論 30 參考文獻 32 實驗圖表 36 | |
dc.language.iso | zh-TW | |
dc.title | 最佳化D型肝炎病毒在HepG2-NTCP-C4細胞的感染 | zh_TW |
dc.title | Optimization of hepatitis D virus infection in HepG2-NTCP-C4 cell model | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 葉秀慧,趙玫 | |
dc.subject.keyword | D型肝炎病毒,B型肝炎病毒,病毒感染率,D型肝炎病毒的複製, | zh_TW |
dc.subject.keyword | Hepatitis D virus,Hepatitis B Virus,HDV infection,HDV replication, | en |
dc.relation.page | 49 | |
dc.identifier.doi | 10.6342/NTU201703726 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-17 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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