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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳培哲(Pei-Jer Chen) | |
| dc.contributor.author | Shao-Wei Tsai | en |
| dc.contributor.author | 蔡少瑋 | zh_TW |
| dc.date.accessioned | 2021-06-16T02:26:52Z | - |
| dc.date.available | 2017-09-25 | |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-04 | |
| dc.identifier.citation | 1. Ganem, D. and A.M. Prince, Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med, 2004. 350(11): p. 1118-29.
2. Lozano, R., et al., Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 2012. 380(9859): p. 2095-128. 3. Chan, H.L. and J.J. Sung, Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis, 2006. 26(2): p. 153-61. 4. McMahon, B.J., Epidemiology and natural history of hepatitis B. Semin Liver Dis, 2005. 25 Suppl 1: p. 3-8. 5. Bremer, C.M., et al., N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus. J Hepatol, 2011. 55(1): p. 29-37. 6. Iwarson, S., et al., Neutralization of hepatitis B virus infectivity by a murine monoclonal antibody: an experimental study in the chimpanzee. J Med Virol, 1985. 16(1): p. 89-96. 7. Ni, Y., et al., The pre-s2 domain of the hepatitis B virus is dispensable for infectivity but serves a spacer function for L-protein-connected virus assembly. J Virol, 2010. 84(8): p. 3879-88. 8. Salisse, J. and C. Sureau, A function essential to viral entry underlies the hepatitis B virus 'a' determinant. J Virol, 2009. 83(18): p. 9321-8. 9. Shearer, M.H., et al., Structural characterization of viral neutralizing monoclonal antibodies to hepatitis B surface antigen. Mol Immunol, 1998. 35(18): p. 1149-60. 10. Gripon, P., et al., Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity. Virology, 1995. 213(2): p. 292-9. 11. Rizzetto, M. and A. Ciancio, Epidemiology of hepatitis D. Semin Liver Dis, 2012. 32(3): p. 211-9. 12. Rizzetto, M., The delta agent. Hepatology, 1983. 3(5): p. 729-37. 13. Rosina, F., et al., Changing pattern of chronic hepatitis D in Southern Europe. Gastroenterology, 1999. 117(1): p. 161-6. 14. Kos, A., et al., The hepatitis delta (delta) virus possesses a circular RNA. Nature, 1986. 323(6088): p. 558-60. 15. Lai, M.M., The molecular biology of hepatitis delta virus. Annu Rev Biochem, 1995. 64: p. 259-86. 16. Branch, A.D., et al., An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus. Science, 1989. 243(4891): p. 649-52. 17. Chao, M., S.Y. Hsieh, and J. Taylor, Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication. J Virol, 1990. 64(10): p. 5066-9. 18. Casey, J.L., et al., Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci U S A, 1992. 89(15): p. 7149-53. 19. Jayan, G.C. and J.L. Casey, Inhibition of hepatitis delta virus RNA editing by short inhibitory RNA-mediated knockdown of ADAR1 but not ADAR2 expression. J Virol, 2002. 76(23): p. 12399-404. 20. Wong, S.K. and D.W. Lazinski, Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc Natl Acad Sci U S A, 2002. 99(23): p. 15118-23. 21. Chang, F.L., et al., The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A, 1991. 88(19): p. 8490-4. 22. Watashi, K., et al., NTCP and beyond: opening the door to unveil hepatitis B virus entry. Int J Mol Sci, 2014. 15(2): p. 2892-905. 23. Lamas Longarela, O., et al., Proteoglycans act as cellular hepatitis delta virus attachment receptors. PLoS One, 2013. 8(3): p. e58340. 24. Leistner, C.M., S. Gruen-Bernhard, and D. Glebe, Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol, 2008. 10(1): p. 122-33. 25. Schulze, A., P. Gripon, and S. Urban, Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology, 2007. 46(6): p. 1759-68. 26. Cooper, A. and Y. Shaul, Clathrin-mediated endocytosis and lysosomal cleavage of hepatitis B virus capsid-like core particles. J Biol Chem, 2006. 281(24): p. 16563-9. 27. Huang, H.C., et al., Entry of hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent endocytosis. J Virol, 2012. 86(17): p. 9443-53. 28. Macovei, A., et al., Hepatitis B virus requires intact caveolin-1 function for productive infection in HepaRG cells. J Virol, 2010. 84(1): p. 243-53. 29. Yan, H., et al., Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife, 2012. 1: p. e00049. 30. Anwer, M.S. and B. Stieger, Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters. Pflugers Arch, 2014. 466(1): p. 77-89. 31. Urban, S., et al., Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology, 2014. 147(1): p. 48-64. 32. Iwamoto, M., et al., Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem Biophys Res Commun, 2014. 443(3): p. 808-13. 33. Ni, Y., et al., Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology, 2014. 146(4): p. 1070-83. 34. Yan, H., et al., Molecular determinants of hepatitis B and D virus entry restriction in mouse sodium taurocholate cotransporting polypeptide. J Virol, 2013. 87(14): p. 7977-91. 35. Gripon, P., et al., Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. J Virol, 1988. 62(11): p. 4136-43. 36. Gudima, S., et al., Primary human hepatocytes are susceptible to infection by hepatitis delta virus assembled with envelope proteins of woodchuck hepatitis virus. J Virol, 2008. 82(15): p. 7276-83. 37. Gudima, S., et al., Assembly of hepatitis delta virus: particle characterization, including the ability to infect primary human hepatocytes. J Virol, 2007. 81(7): p. 3608-17. 38. Gripon, P., et al., Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci U S A, 2002. 99(24): p. 15655-60. 39. Sureau, C., The use of hepatocytes to investigate HDV infection: the HDV/HepaRG model. Methods Mol Biol, 2010. 640: p. 463-73. 40. Kuo, M.Y., M. Chao, and J. Taylor, Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol, 1989. 63(5): p. 1945-50. 41. Mu, J.J., D.S. Chen, and P.J. Chen, 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, 2001. 75(19): p. 9087-95. 42. Wang, C.J., et al., Small-form hepatitis B surface antigen is sufficient to help in the assembly of hepatitis delta virus-like particles. J Virol, 1991. 65(12): p. 6630-6. 43. Huang, C.R., et al., Lysine-71 in the large delta antigen of hepatitis delta virus clade 3 modulates its localization and secretion. Virus Res, 2012. 170(1-2): p. 75-84. 44. Mu, J.J., et al., Characterization of the phosphorylated forms and the phosphorylated residues of hepatitis delta virus delta antigens. J Virol, 1999. 73(12): p. 10540-5. 45. Schulze, A., et al., Hepatocyte polarization is essential for the productive entry of the hepatitis B virus. Hepatology, 2012. 55(2): p. 373-83. 46. Borst, P. and R.O. Elferink, Mammalian ABC transporters in health and disease. Annu Rev Biochem, 2002. 71: p. 537-92. 47. Schafer, G., M.J. Blumenthal, and A.A. Katz, Interaction of human tumor viruses with host cell surface receptors and cell entry. Viruses, 2015. 7(5): p. 2592-617. 48. Meredith, L.W., et al., Hepatitis C virus entry: beyond receptors. Rev Med Virol, 2012. 22(3): p. 182-93. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53643 | - |
| dc.description.abstract | 全球乙型肝炎病毒感染的患者目前估計約2.4億人，而慢性感染乙型肝炎病毒的病人有更高的風險發展為肝纖維化以及肝硬化並發展成肝癌等肝病；丁型肝炎病毒是乙型肝炎病毒的衛星病毒，在生活史中需要利用乙型肝炎病毒的外套膜進行感染，共同感染乙型與丁型肝炎則會加速進展成更嚴重的肝病，目前全世界約有1500到2000萬人感染丁型肝炎病毒，這兩種病毒在全球造成相當大的公共衛生議題。先前乙型或丁型肝炎的感染研究的困難之處在於沒有一個可以感染的小鼠模式也沒有一個適合感染的細胞株系統，在近期的研究發現到其中一個乙型肝炎的接受器-鈉離子牛磺膽酸共轉運蛋白 (NTCP)，並在實驗中證實可以提供乙型以及丁型肝炎病毒進入細胞。基於這項證據，本篇研究利用穩定過表現鈉離子牛磺膽酸共轉運蛋白的肝癌細胞株進行乙型以及丁型肝炎病毒的感染測試，檢查各個細胞株對於這兩種病毒的感染效率。研究中發現：在擁有相當的鈉離子牛磺膽酸共轉運蛋白表現量的情況下，從HepaG2 肝癌細胞株篩選出來SW1細胞和其他細胞株比較起來對於乙型肝炎病毒的感染有比較高的效率，而丁型肝炎病毒的感染似乎並不成功。利用目前的結果可以來推論表現鈉離子牛磺膽酸共轉運蛋白不一定能夠足以讓乙型或丁型肝炎進入細胞，不過利用目前建立的細胞株可以讓我們日後更進一步地分析其他促進這兩種肝癌病毒進入細胞的因子，或者是作為分析細胞對於病毒所產生抗病毒機制的工具。 | zh_TW |
| dc.description.abstract | There are approximately 240 million people are chronically infected with hepatitis B virus (HBV) worldwide. Patients who infected with HBV are at high risk for progression to cirrhosis and liver failure or liver cancer, and more than 780000 people die every year owing to the complications of HBV. Hepatitis Delta (HDV) virus is the smallest virus which can infect human. HDV is known to be a satellite virus of Hepatitis B virus (HBV), and it depends on envelope protein of HBV to process the entry and virus particle assembly in virus life cycle. HDV infection causes severe acute and chronic liver disease of HBV carriers. There are approximately 15 to 20 million people infected HDV (around 5% of HBs Ag carriers). Both HBV and HDV related liver diseases are still a major public health problem. There were no susceptible infection model of HBV and HDV because of lacking the knowledge of HBV entry. Recently, NTCP (sodium taurocholate cotransporting polypeptide) was identified as one of HBV entry receptors. Many studies showed that NTCP over expression rendered non-susceptible hepatoma cell lines susceptible to HBV and HDV. Thus our group generated the stably overexpressing ntcp HepaG2 cell line SW1 which is susceptible to HBV while with low efficiency to HDV. By taking advantage of this cell model, we can research other factors that involved in viral entry and the mechanism of antiviral pathways in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T02:26:52Z (GMT). No. of bitstreams: 1 ntu-104-R02445118-1.pdf: 1856277 bytes, checksum: a046c5a7dc12b8f85a7ecb0e4c18891a (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 國立臺灣大學士學位論文口試委員會審定書 5
中文摘要 6 ABSTRACT 7 LIST OF ABBREVIATIONS 9 CHAPTER 1: INTRODUCTION 10 1.1 Virology of HBV 10 1.2 Virology of HDV 11 1.3 The virus entry and discovery of NTCP 12 1.4 HBV and HDV infection models 13 1.5 Aims of thesis research 14 CHAPTER 2: MATERIALS AND METHODS 15 2.1 Plasmid construct 15 2.2 Cell culture and DNA transfection 15 2.3 Virus preparation and quantification 17 2.4 HBV and HDV infection 18 2.5 Biological analysis 18 CHAPTER 3: RESULTS 21 3.1 The establishment of NTCP stable expressing cell lines 21 3.2 The HBV infection in NTCP stable expressing cell lines 22 3.3 The quantification of the HDV viral particles 22 3.4 The HDV infection in NTCP stable expressing cell lines 23 CHATER 4: DISCUSSIONS 25 CHAPTER 5: CONCLUDING REMARKS 27 CHATER 6: FIGUREs 28 Figure 1 Result of G418 selection of NTCP stable clones. 29 Figure 2. The HBV infection in NTCP expressing cells. 32 Figure 3 Quantification of HDV viral particles. 34 Figure 4 The HDV infection in NTCP expressing cells. 37 REFERENCES 39 | |
| dc.language.iso | en | |
| dc.subject | 鈉離子牛磺膽酸共轉運蛋白 | zh_TW |
| dc.subject | 乙型肝炎 | zh_TW |
| dc.subject | 丁型肝炎 | zh_TW |
| dc.subject | NTCP | en |
| dc.subject | HBV | en |
| dc.subject | HDV | en |
| dc.title | 以過表現鈉離子牛磺膽酸共轉運蛋白之肝癌細胞株建立乙型與丁型肝炎病毒感染模型 | zh_TW |
| dc.title | Establishment of Hepatitis B and D Infection Model in Sodium Taurocholate Cotransporting Peptide (NTCP) Overexpressing Hepatoma Cell Line | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 趙玫(Mei Chao),陶秘華(Mi-Hua Tao) | |
| dc.subject.keyword | 乙型肝炎,丁型肝炎,鈉離子牛磺膽酸共轉運蛋白, | zh_TW |
| dc.subject.keyword | HBV,HDV,NTCP, | en |
| dc.relation.page | 42 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-04 | |
| 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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