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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳培哲(Pei-Jer Chen) | |
| dc.contributor.author | Ze-Fong Li | en |
| dc.contributor.author | 李澤峰 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:27:56Z | - |
| dc.date.available | 2021-10-01 | |
| dc.date.available | 2022-11-24T03:27:56Z | - |
| dc.date.copyright | 2021-10-01 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-31 | |
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Paraskevopoulou S, Pirzer F, Goldmann N, Schmid J, Corman VM, Gottula LT, Schroeder S, Rasche A, Muth D, Drexler JF, Heni AC, Eibner GJ, Page RA, Jones TC, Muller MA, Sommer S, Glebe D, Drosten C (2020) Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus. Proc Natl Acad Sci U S A. 117:17977-83. PMID: 32651267. doi: 10.1073/pnas.2006750117. 5. Le Gal, F., Brichler et al. (2017). Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains. Hepatology, 66(6), 1826-1841. doi:10.1002/hep.29574 6. Fouad, R., Abdo, M., Eldeen, H. G., Sabry, D., Atef, M., Ahmed, R., Zayed, N. (2016). Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D. J Med Virol, 88(5), 837-842. doi:10.1002/jmv.24412 7. Sadeghian, H et al. (2015). Distribution of hepatitis delta virus genotypes in mashhad, northeast iran. Jundishapur J Microbiol, 8(2), e14908. doi:10.5812/jjm.14908 8. Chen, H. Y., Shen, D. T et al. (2019). Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis. Gut, 68(3), 512-521. doi:10.1136/gutjnl-2018-316601 9. Alvarado-Mora, M. V., Locarnini, S., Rizzetto, M., Pinho, J. R. (2013). An update on HDV: virology, pathogenesis and treatment. Antivir Ther, 18(3 Pt B), 541-548. doi:10.3851/imp2598 10. Bonino, F., Smedile, A. (1986). Delta agent (type D) hepatitis. Semin Liver Dis, 6(1), 28-33. doi:10.1055/s-2008-1040790 11. Schulze, A., Gripon, P. Urban, S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology 46, 1759-1768, doi:10.1002/hep.21896 (2007). (12) 12. Leistner, C. M., Gruen-Bernhard, S. Glebe, D. Role of glycosaminoglycans for binding and infection of hepatitis B virus. 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Genomic but not antigenomic hepatitis delta virus RNA is preferentially exported from the nucleus immediately after synthesis and processing. J Virol, 76(8), 3928-3935. doi:10.1128/jvi.76.8.3928-3935.2002 33. Li, Y. J., Macnaughton, T., Gao, L., Lai, M. M. (2006). RNA-templated replication of hepatitis delta virus: genomic and antigenomic RNAs associate with different nuclear bodies. J Virol, 80(13), 6478-6486. doi:10.1128/jvi.02650-05 34. Wild, T., Cramer, P. (2012). Biogenesis of multisubunit RNA polymerases. Trends Biochem Sci, 37(3), 99-105. doi:10.1016/j.tibs.2011.12.001 35. Verrier, E. R. et al. (2020). Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets. Gut, 69(1), 158-167. doi:10.1136/gutjnl-2018-317065 36. Sikorski, T. W., and S. Buratowski. 2009. The basal initiation machinery: beyond the general transcription factors. Curr Opin Cell Biol 21:344-51. 37. Saunders, A., L. J. Core, and J. T. Lis. 2006. Breaking barriers to transcription elongation. Nat Rev Mol Cell Biol 7:557-67. 38. Buratowski, S. 2005. Connections between mRNA 3'' end processing and transcription termination. Curr Opin Cell Biol 17:257-61. 39. Greco-Stewart, V. S., Schissel, E., Pelchat, M. (2009). The hepatitis delta virus RNA genome interacts with the human RNA polymerases I and III. Virology, 386(1), 12-15. doi:10.1016/j.virol.2009.02.007 40. Nesser, N. K., Peterson, D. O., Hawley, D. K. (2006). RNA polymerase II subunit Rpb9 is important for transcriptional fidelity in vivo. Proc Natl Acad Sci U S A, 103(9), 3268-3273. doi:10.1073/pnas.0511330103 41. Sein, H., Reinmets, K., Peil, K., Kristjuhan, K., Värv, S., Kristjuhan, A. (2018). Rpb9-deficient cells are defective in DNA damage response and require histone H3 acetylation for survival. Sci Rep, 8(1), 2949. doi:10.1038/s41598-018-21110-9 42. Hull, M. W., McKune, K., Woychik, N. A. (1995). RNA polymerase II subunit RPB9 is required for accurate start site selection. Genes Dev, 9(4), 481-490. doi:10.1101/gad.9.4.481 43. Malik, S., Roeder, R. G. (2003). Isolation and functional characterization of the TRAP/mediator complex. Methods Enzymol, 364, 257-284. doi:10.1016/s0076-6879(03)64015-2 44. Modahl, L. E., Macnaughton, T. B., Zhu, N., Johnson, D. L., Lai, M. M. (2000). RNA-Dependent replication and transcription of hepatitis delta virus RNA involve distinct cellular RNA polymerases. Mol Cell Biol, 20(16), 6030-6039. doi:10.1128/mcb.20.16.6030-6039.2000 45. Taylor, J. M. Hepatitis D Virus Replication. Cold Spring Harb Perspect Med 5, doi:10.1101/cshperspect.a021568 (2015). 46. Tandon, N., Thakkar, K. N., LaGory, E. L., Liu, Y., Giaccia, A. J. (2018). Generation of Stable Expression Mammalian Cell Lines Using Lentivirus. Bio Protoc, 8(21). doi:10.21769/BioProtoc.3073 47. Mu, J. J ., Chen, D. S., Chen, P. J. (2001). The conserved serine 177 in the delta antigen of hepatitis delta virus is one putative phosphorylation site and is required for efficient viral RNA replication. J Virol, 75(19), 9087-9095. doi:10.1128/jvi.75.19.9087-9095.2001 48. Hong, S. Y., Chen, P. J. (2010). Phosphorylation of serine 177 of the small hepatitis delta antigen regulates viral antigenomic RNA replication by interacting with the processive RNA polymerase II. J Virol, 84(3), 1430-1438. doi:10.1128/jvi.02083-09 49. Aibara, S., Schilbach, S., Cramer, P. (2021). Structures of mammalian RNA polymerase II pre-initiation complexes. Nature, 594(7861), 124-128. doi:10.1038/s41586-021-03554-8 50. Tuan, J. C., Zhai, W., Comai, L. (1999). Recruitment of TATA-binding protein-TAFI complex SL1 to the human ribosomal DNA promoter is mediated by the carboxy-terminal activation domain of upstream binding factor (UBF) and is regulated by UBF phosphorylation. Mol Cell Biol, 19(4), 2872-2879. doi:10.1128/mcb.19.4.2872 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81047 | - |
| dc.description.abstract | D肝炎病毒是B肝炎病毒的衛星病毒，根據過去統計資料，全球約有1500~2000萬人感染B型肝炎和D型肝炎病。根據2020年的綜合分析，目前全球人口有約10.6% 的B型肝炎帶原者 (約6200~7200百萬人) 同時感染B及D型肝炎病毒。D型肝炎病毒感染分成兩種形式，其一是B肝炎病毒和D肝炎病毒同時共同感染，另一種為患有慢性B肝病毒感染患者再被D肝病毒感染。受到HBV和HDV感染可能會導致最嚴重的肝炎疾病 - 猛爆性肝炎。D肝病毒帶有1.7 kb的Genomic RNA 並會產生一種病毒蛋白-delta抗原，delta抗原 (HDAg)，由於該蛋白不具有聚合酶活性。因此，D型肝炎病毒必須利用部分宿主酵素來完成其生命週期。目前關於 D肝炎病毒複製中涉及的宿主酵素有兩種主要理論。其中一派認為RNA 聚合酶 II 參與了基因組和反基因組 RNA 複製，因為這兩個過程都對低劑量的 RNA 聚合酶 II 敏感抑製劑 α-鵝膏菌素敏感，而另一派認為 RNA聚合酶II以外的聚合酶可能參與基因組 RNA 的合成，因為α-鵝膏菌素在高濃度下無法阻斷反基因組 RNA 的合成。迄今為止，是否有 RNA 聚合酶 II以外的聚合酶否參與 D肝炎病毒的複製仍存有爭議。除了抑制劑實驗結果外，將RNA聚合酶II上的次單位以小分子干擾RNA減少表現後會使D型肝炎病毒感染率顯著下降。另一個研究指出，部分純化的RNA聚合酶II可以利用D型肝炎病毒的RNA在體外進行轉錄作用。基於前人研究，因此我們假設 RNA 聚合酶 II 參與了 D肝炎病毒的複製過程。為了驗證該假說，我們試圖透過建立在 RPB9（RNA 聚合酶 II 的一個次單位）上過量表達FLAG- RPB9的海拉細胞 (HeLa cell) 作為純化 RNA 聚合酶II，並分析 RNA 聚合酶 II 是否可以在體外轉錄D肝炎病毒的RNA。本研究提供RNA 聚合酶II純化所需的細胞株，為未來解決RNA 聚合酶II參與在D肝病毒複製過程中的爭議。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:27:56Z (GMT). No. of bitstreams: 1 U0001-2308202113465800.pdf: 8004087 bytes, checksum: 4c014aa59046e8ad800f9e1f5901c713 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "國立台灣大學碩士學位口試委員會審定書 2 致謝 3 摘要 4 Abstract 5 List of abbreviation 9 CHAPTER I: Introduction 10 1.1 Introduction of Hepatitis Delta Virus (HDV) 10 1.1.1 The discovery of HDV 10 1.1.2 Epidemiology and clinical significance 10 1.2 The molecular biology of HDV 11 1.2.1 Virion structure 11 1.2.2 Current proposed HDV life cycle 11 1.3 The dispute of HDV RNA replication 13 1.4 RNA polymerase II 13 1.5 RNA polymerase I, III 14 1.6 Working hypothesis 14 CHAPTER II: Material and methods 16 2.1 Plasmid constructs 16 2.1.1 FLAG-RPB9 plasmid (hRPB9-pVP5) 16 2.1.2 pCR3.1_HDV(I)_221T/219C_PI 16 2.2 Cell culture and DNA transfection 17 2.2.1 HeLa cell 17 2.2.2 FLAG-expressing HeLa single cell clone (F1~F3) 17 2.2.3 Lipofectamine 2000 transfection 18 2.3 Western blot 18 2.4 Northern blot 19 2.5 Immunoprecipitation 20 CHAPTER III: Results 21 3.1 Establishing FLAG-RPB9 expressing HeLa cell 21 3.1.1 HeLa bulk cell clones 21 3.1.2 HeLa single cell clone 22 CHAPTER IV: Discussion 23 CHAPTER V: Concluding remarks 25 CHAPTER VI: Experimental Figures tables 26 Figure 1. Virion structure of Hepatitis Delta Virus (HDV) 26 Figure 2. Currently proposed Hepatitis Delta Virus replication cycle 27 Figure 3. FLAG-RPB9 plasmid from Prof. Robert G. Roeder of Rockefeller University 28 Figure 4. Isolates of HeLa cells transfected with FLAG-RPB9 after G418 selection (20 days post-selection) 29 Figure 5. Validating HDV replication in HeLa cell stably expressing FLAG-RPB9 30 Figure 6. FLAG-RPB9 expressing HeLa cell clones after limiting dilution 31 Figure 7. Proposed experiment –RNA polymerase II purification34 IP experiment 32 Figure 8. Immunoprecipitation using HeLa F2 cell by FLAG M2 antibody 33 Figure 9. Trouble shooting in IP experiment 34 Table 1. Antibodies used for western blot and immunoprecipitation 35 Table 2. G418-selection of HeLa cell transfected with FLAG-RPB9 plasmid 36 Supplementary data 1. Human cell line typing of HeLa 37 References 42" | |
| dc.language.iso | en | |
| dc.subject | D肝病毒複製 | zh_TW |
| dc.subject | D型肝炎病毒 | zh_TW |
| dc.subject | 小型Delta 抗原 | zh_TW |
| dc.subject | RNA 聚合酶 II | zh_TW |
| dc.subject | Small Delta Antigen | en |
| dc.subject | HDV replication | en |
| dc.subject | RNA polymerase II | en |
| dc.subject | Hepatitis Delta Virus | en |
| dc.title | 建立表現FLAG-RPB9細胞株研究RNA 聚合酶II 對於D型肝炎複製所扮演的角色 | zh_TW |
| dc.title | Establishment of FLAG-RPB9 expressing cell line to study Hepatitis Delta Virus replication by cellular RNA polymerase II | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.advisor-orcid | 陳培哲(0000-0001-8316-3785) | |
| dc.contributor.oralexamcommittee | 趙玫(Hsin-Tsai Liu),陳宏達(Chih-Yang Tseng) | |
| dc.subject.keyword | D型肝炎病毒,小型Delta 抗原,RNA 聚合酶 II,D肝病毒複製, | zh_TW |
| dc.subject.keyword | Hepatitis Delta Virus,Small Delta Antigen,RNA polymerase II,HDV replication, | en |
| dc.relation.page | 48 | |
| dc.identifier.doi | 10.6342/NTU202102614 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-31 | |
| 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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