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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 微生物學科所
Please use this identifier to cite or link to this item: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95099
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???org.dspace.app.webui.jsptag.ItemTag.dcfield???ValueLanguage
dc.contributor.advisor陳培哲zh_TW
dc.contributor.advisorPei-Jer Chenen
dc.contributor.author梁維綸zh_TW
dc.contributor.authorWei-Lun Liangen
dc.date.accessioned2024-08-28T16:15:38Z-
dc.date.available2024-08-29-
dc.date.copyright2024-08-28-
dc.date.issued2024-
dc.date.submitted2024-08-02-
dc.identifier.citation1. Shepard, C.W., et al., Hepatitis B virus infection: epidemiology and vaccination. Epidemiologic reviews, 2006. 28(1): p. 112-125.
2. Rajbhandari, R. and R.T. Chung, Screening for hepatitis B virus infection: a public health imperative. Annals of internal medicine, 2014. 161(1): p. 76-77.
3. Ott, J., et al., Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine, 2012. 30(12): p. 2212-2219.
4. Ozakyol, A., Global epidemiology of hepatocellular carcinoma (HCC epidemiology). Journal of gastrointestinal cancer, 2017. 48: p. 238-240.
5. Yang, H.-I., et al., Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. Journal of the National Cancer Institute, 2008. 100(16): p. 1134-1143.
6. Tavakolpour, S., et al., Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B infection during pregnancy: a systematic review. Infectious Diseases, 2018. 50(2): p. 95-106.
7. Asim, M., et al., Significance of anti-HBc screening of blood donors & its association with occult hepatitis B virus infection: Implications for blood transfusion. Indian Journal of Medical Research, 2010. 132(3): p. 312-317.
8. Dembek, C., U. Protzer, and M. Roggendorf, Overcoming immune tolerance in chronic hepatitis B by therapeutic vaccination. Current opinion in virology, 2018. 30: p. 58-67.
9. Ramanan, V., et al., CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus. Scientific reports, 2015. 5(1): p. 10833.
10. Yuen, M.-F., et al., Hepatitis B virus infection. Nature reviews Disease primers, 2018. 4(1): p. 1-20.
11. Moucari, R., O. Lada, and P. Marcellin, Chronic hepatitis B: back to the future with HBsAg. Expert Review of Anti-infective Therapy, 2009. 7(6): p. 633-636.
12. Tsukuda, S. and K. Watashi, Hepatitis B virus biology and life cycle. Antiviral research, 2020. 182: p. 104925.
13. Candotti, D. and J.-P. Allain, Biological and clinical significance of hepatitis B virus RNA splicing: an update. Annals of Blood, 2017. 2(4).
14. Kremsdorf, D., et al., Alternative splicing of viral transcripts: the dark side of HBV. Gut, 2021. 70(12): p. 2373-2382.
15. Lim, C.S., et al., Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes. Microbial genomics, 2021. 7(1): p. 000492.
16. Su, T.-S., et al., Analysis of hepatitis B virus transcripts in infected human livers. Hepatology, 1989. 9(2): p. 180-185.
17. Somiya, M., et al., Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan. Virology, 2016. 497: p. 23-32.
18. Yan, H., et al., Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. elife, 2012. 1: p. e00049.
19. Rabe, B., D. Glebe, and M. Kann, Lipid-mediated introduction of hepatitis B virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events. Journal of virology, 2006. 80(11): p. 5465-5473.
20. Qi, Y., et al., DNA polymerase κ is a key cellular factor for the formation of covalently closed circular DNA of hepatitis B virus. PLoS pathogens, 2016. 12(10): p. e1005893.
21. Hu, J. and C. Seeger, Hepadnavirus genome replication and persistence. Cold Spring Harbor perspectives in medicine, 2015. 5(7): p. a021386.
22. Blondot, M.-L., V. Bruss, and M. Kann, Intracellular transport and egress of hepatitis B virus. Journal of hepatology, 2016. 64(1): p. S49-S59.
23. McCracken, S., et al., 5′-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II. Genes & development, 1997. 11(24): p. 3306-3318.
24. Zeng, C. and S.M. Berget, Participation of the C-terminal domain of RNA polymerase II in exon definition during pre-mRNA splicing. Molecular and cellular biology, 2000. 20(21): p. 8290-8301.
25. Wilkinson, M.E., C. Charenton, and K. Nagai, RNA splicing by the spliceosome. Annual review of biochemistry, 2020. 89(1): p. 359-388.
26. Licatalosi, D.D., et al., Functional interaction of yeast pre-mRNA 3′ end processing factors with RNA polymerase II. Molecular cell, 2002. 9(5): p. 1101-1111.
27. Murthy, K. and J.L. Manley, The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3'-end formation. Genes & development, 1995. 9(21): p. 2672-2683.
28. Mitchell, S.F. and R. Parker, Principles and properties of eukaryotic mRNPs. Molecular cell, 2014. 54(4): p. 547-558.
29. Dufu, K., et al., ATP is required for interactions between UAP56 and two conserved mRNA export proteins, Aly and CIP29, to assemble the TREX complex. Genes & development, 2010. 24(18): p. 2043-2053.
30. Umlauf, D., et al., The human TREX-2 complex is stably associated with the nuclear pore basket. Journal of cell science, 2013. 126(12): p. 2656-2667.
31. Lin, D.H., et al., Structural and functional analysis of mRNA export regulation by the nuclear pore complex. Nature communications, 2018. 9(1): p. 2319.
32. Folkmann, A.W., et al., Dbp5, Gle1-IP6 and Nup159: a working model for mRNP export. Nucleus, 2011. 2(6): p. 540-548.
33. Brennan, C.M., I.-E. Gallouzi, and J.A. Steitz, Protein ligands to HuR modulate its interaction with target mRNAs in vivo. The Journal of cell biology, 2000. 151(1): p. 1-14.
34. Gallouzi, I.-E., C.M. Brennan, and J.A. Steitz, Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. Rna, 2001. 7(9): p. 1348-1361.
35. Wang, Y., et al., ANP32A and ANP32B are key factors in the Rev-dependent CRM1 pathway for nuclear export of HIV-1 unspliced mRNA. Journal of Biological Chemistry, 2019. 294(42): p. 15346-15357.
36. Topisirovic, I., et al., Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export‐competent RNP. The EMBO journal, 2009. 28(8): p. 1087-1098.
37. Piserà, A., A. Campo, and S. Campo, Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment. Journal of Genetics and Genomics, 2018. 45(1): p. 13-24.
38. Volpon, L., et al., A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery. Rna, 2017. 23(6): p. 927-937.
39. Monecke, T., et al., Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP. Science, 2009. 324(5930): p. 1087-1091.
40. Hutten, S., et al., The Nup358-RanGAP complex is required for efficient importin α/β-dependent nuclear import. Molecular biology of the cell, 2008. 19(5): p. 2300-2310.
41. Gales, J.P., et al., Strength in diversity: nuclear export of viral RNAs. Viruses, 2020. 12(9): p. 1014.
42. Müller-McNicoll, M., et al., SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export. Genes & development, 2016. 30(5): p. 553-566.
43. Boehm, V. and N.H. Gehring, Exon junction complexes: supervising the gene expression assembly line. Trends in Genetics, 2016. 32(11): p. 724-735.
44. Le Hir, H., et al., The exon–exon junction complex provides a binding platform for factors involved in mRNA export and nonsense‐mediated mRNA decay. The EMBO journal, 2001.
45. Watts, J.M., et al., Architecture and secondary structure of an entire HIV-1 RNA genome. Nature, 2009. 460(7256): p. 711-716.
46. Emery, A. and R. Swanstrom, HIV-1: to splice or not to splice, that is the question. Viruses, 2021. 13(2): p. 181.
47. Fernandes, J., B. Jayaraman, and A. Frankel, The HIV-1 Rev response element: an RNA scaffold that directs the cooperative assembly of a homo-oligomeric ribonucleoprotein complex. RNA biology, 2012. 9(1): p. 6-11.
48. Robertson-Anderson, R.M., et al., Single-molecule studies reveal that DEAD box protein DDX1 promotes oligomerization of HIV-1 Rev on the Rev response element. Journal of molecular biology, 2011. 410(5): p. 959-971.
49. Yedavalli, V.S., et al., Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell, 2004. 119(3): p. 381-392.
50. Kim, S., et al., Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. Journal of virology, 1989. 63(9): p. 3708-3713.
51. Tabernero, C., et al., The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function. Journal of virology, 1996. 70(9): p. 5998-6011.
52. Aibara, S., et al., The principal mRNA nuclear export factor NXF1: NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA. Nucleic acids research, 2015. 43(3): p. 1883-1893.
53. Meiering, C.D. and M.L. Linial, Reactivation of a complex retrovirus is controlled by a molecular switch and is inhibited by a viral protein. Proceedings of the National Academy of Sciences, 2002. 99(23): p. 15130-15135.
54. Lindemann, D., et al., The unique, the known, and the unknown of spumaretrovirus assembly. Viruses, 2021. 13(1): p. 105.
55. Wang, X. and J. Hu, Distinct requirement for two stages of protein-primed initiation of reverse transcription in hepadnaviruses. Journal of virology, 2002. 76(12): p. 5857-5865.
56. Bodem, J., et al., Foamy virus nuclear RNA export is distinct from that of other retroviruses. Journal of virology, 2011. 85(5): p. 2333-2341.
57. Lim, C.S. and C.M. Brown, Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element. RNA biology, 2016. 13(9): p. 743-747.
58. Huang, J. and T.J. Liang, A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products. Molecular and cellular biology, 1993. 13(12): p. 7476-7486.
59. Zang, W.-Q., et al., Role of polypyrimidine tract binding protein in the function of the hepatitis B virus posttranscriptional regulatory element. Journal of virology, 2001. 75(22): p. 10779-10786.
60. Li, Y., et al., Role of glyceraldehyde-3-phosphate dehydrogenase binding to hepatitis B virus posttranscriptional regulatory element in regulating expression of HBV surface antigen. Archives of virology, 2009. 154: p. 519-524.
61. Horke, S., et al., Molecular characterization of the human La protein· hepatitis B virus RNA. B interaction in vitro. Journal of Biological Chemistry, 2002. 277(38): p. 34949-34958.
62. Chi, B., et al., A Sub-Element in PRE enhances nuclear export of intronless mRNAs by recruiting the TREX complex via ZC3H18. Nucleic acids research, 2014. 42(11): p. 7305-7318.
63. Yang, C.-C., et al., Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the cellular NXF1-p15 machinery. PLoS One, 2014. 9(10): p. e106683.
64. Makokha, G.N., et al., Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP. Scientific reports, 2019. 9(1): p. 8462.
65. Yang, C.-C., et al., CRM1-spike-mediated nuclear export of hepatitis B virus encapsidated viral RNA. Cell Reports, 2022. 38(10).
66. Wettengel, J.M., et al., Rapid and robust continuous purification of high-titer hepatitis B Virus for in vitro and in vivo applications. Viruses, 2021. 13(8): p. 1503.
67. Suzuki, T., et al., Intravenous injection of naked plasmid DNA encoding hepatitis B virus (HBV) produces HBV and induces humoral immune response in mice. Biochemical and biophysical research communications, 2003. 300(3): p. 784-788.
68. Champlot, S., et al., An efficient multistrategy DNA decontamination procedure of PCR reagents for hypersensitive PCR applications. PloS one, 2010. 5(9): p. e13042.
69. Ko, C., et al., Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels. Journal of hepatology, 2018. 69(6): p. 1231-1241.
70. Tu, T., et al., A novel method to precisely quantify hepatitis B virus covalently closed circular (ccc) DNA formation and maintenance. Antiviral Research, 2020. 181: p. 104865.
71. Lucifora, J., et al., Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. Journal of hepatology, 2011. 55(5): p. 996-1003.
72. Liu, W., et al., Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome. Nature Communications, 2023. 14(1): p. 4663.
73. Kong, X., et al., JMJD2D stabilises and cooperates with HBx protein to promote HBV transcription and replication. JHEP Reports, 2023. 5(10): p. 100849.
74. Sekiba, K., et al., HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA. Journal of Hepatology, 2022. 76(1): p. 53-62.
75. Su, K.-J. and Y.-L. Yu, Downregulation of SHIP2 by hepatitis B virus X promotes the metastasis and chemoresistance of hepatocellular carcinoma through SKP2. Cancers, 2019. 11(8): p. 1065.
76. Zhu, M., et al., HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway. International Journal of Cancer, 2017. 140(6): p. 1346-1355.
77. Hu, B., et al., Cellular UAP56 interacts with the HBx protein of the hepatitis B virus and is involved in viral RNA nuclear export in hepatocytes. Experimental Cell Research, 2020. 390(1): p. 111929.
78. Niu, C., et al., The Smc5/6 complex restricts HBV when localized to ND10 without inducing an innate immune response and is counteracted by the HBV X protein shortly after infection. PloS one, 2017. 12(1): p. e0169648.
79. Lampertico, P., et al., EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology, 2017. 67(2): p. 370-398.
80. Wang, J., et al., Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. Journal of hepatology, 2016. 65(4): p. 700-710.
81. Prakash, K., et al., High serum levels of pregenomic RNA reflect frequently failing reverse transcription in hepatitis B virus particles. Virology journal, 2018. 15: p. 1-8.
82. van Bömmel, F., et al., Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatology, 2015. 61(1): p. 66-76.
83. Yu, G., et al., A standardized assay for the quantitative detection of serum HBV RNA in chronic hepatitis B patients. Emerging Microbes & Infections, 2022. 11(1): p. 775-785.
84. Lam, A.M., et al., Hepatitis B virus capsid assembly modulators, but not nucleoside analogs, inhibit the production of extracellular pregenomic RNA and spliced RNA variants. Antimicrobial agents and chemotherapy, 2017. 61(8): p. 10.1128/aac. 00680-17.
85. Tsuge, M., et al., Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. Journal of gastroenterology, 2013. 48: p. 1188-1204.
86. Vachon, A., et al., Analytical and clinical validation of 3′ RACE RT-qPCR assay for detection and quantification of hepatitis B virus (HBV) serum RNA. Journal of Clinical Virology Plus, 2022. 2(4): p. 100126.
87. Hindson, B.J., et al., High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Analytical chemistry, 2011. 83(22): p. 8604-8610.
88. Americo, J.L., P.L. Earl, and B. Moss, Droplet digital PCR for rapid enumeration of viral genomes and particles from cells and animals infected with orthopoxviruses. Virology, 2017. 511: p. 19-22.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95099-
dc.description.abstractB型肝炎病毒(HBV)是全球範圍內導致慢性肝病和肝細胞癌的主要原因。理解HBV感染的早期階段,特別是HBV RNA的合成和出口,對於開發有效的診斷和治療策略至關重要。病毒通常擁有獨特的RNA出口機制,使它們能夠成功地利用宿主細胞的機制進行RNA的轉運和表達。例如,HIV通過Rev-RRE系統促進未剪接RNA的出口,Mason-Pfizer猴病毒(MPMV)則利用CTE元素進行RNA的核輸出。本研究旨在探討HBV RNA在感染初期的合成動力學,並希望發現HBV RNA出口的可能機制。利用Northern blot偵測HBV mRNAs能夠在感染後48小時看見3.5 kb preC/pgRNA, 2.4 kb PreS1 RNA, and 2.1 kb PreS2/S RNA 的存在,更進一步以RT-PCR發現在感染12和24小時後只出現剪接型RNA的訊號,並沒有未剪接RNA的存在,但還需要加以證明。另外,我們希望開發一種利用特殊的引子設計的RT-qPCR方法試圖在不處理DNaseI的狀況下偵測HBV RNAs,然而並無法找出合適的引子條件能夠完全避免HBV DNA干擾,所以我們進一步對RNA進行mRNA純化。最後以20 nM 3’Poly(dT)-Adaptor的引子濃度和純化mRNA的方式進行RT-qPCR能夠避免HBV DNA的干擾,然而此方法在偵測不同感染時間點的HBV mRNA靈敏度過低,而且測得的不同感染時間點的Ct值趨勢並不符合Northerm blot的結果。zh_TW
dc.description.abstractHepatitis B virus (HBV) is a major global cause of chronic liver disease and hepatocellular carcinoma. Understanding the early stages of HBV infection, particularly the synthesis and export of HBV RNA, is crucial for developing effective diagnostic and therapeutic strategies. Viruses often possess unique RNA export mechanisms that allow them to successfully utilize host cell machinery for RNA transport and expression. For example, HIV promotes the export of unspliced RNA through the Rev-RRE system, while Mason-Pfizer monkey virus (MPMV) uses the CTE element for RNA nuclear export. This study aims to investigate the kinetics of HBV RNA synthesis during the early stages of infection and to identify potential mechanisms for HBV RNA export. Northern blot analysis revealed the presence of 3.5 kb preC/pgRNA, 2.4 kb PreS1 RNA, and 2.1 kb PreS2/S RNA at 48 hours post-infection. Further RT-PCR analysis showed that only spliced RNA signals were detected at 12 and 24 hours post-infection, with no evidence of unspliced RNA, though further confirmation is needed. Additionally, we aimed to develop an RT-qPCR method using specially designed primers to detect HBV RNAs without DNase I treatment. However, suitable primer conditions to completely avoid HBV DNA interference could not be found. Therefore, we proceeded with mRNA purification. Finally, using a 20 nM 3’Poly(dT)-Adaptor primer concentration and purified mRNA for RT-qPCR successfully avoided HBV DNA interference. Nonetheless, this method had insufficient sensitivity for detecting HBV mRNA at different infection time points, and the Ct value trends did not align with Northern blot results.en
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dc.description.tableofcontents謝辭 i
摘要 ii
ABSTRACT iii
CONTENTS v
CHAPTER 1: INTRODUCTION 1
1.1 Introduction of HBV 1
1.1.1 Epidemiology of HBV 1
1.1.2 HBV genome and structure 2
1.1.3 HBV life cycle 3
1.2 Cellular RNA processing 5
1.2.1 5’ capping 5
1.2.2 Splicing 5
1.2.3 3’ polyadenylation 6
1.3 RNAs export 6
1.3.1 Cellular RNA export 6
1.3.1.1 NXF1-mediated mRNA export 6
1.3.1.2 CRM1-mediated mRNA export 7
1.3.2 Viral RNA export 8
1.3.2.1 Human Immunodeficiency Virus-1 (HIV-1) 9
1.3.2.2 Mason–Pfizer Monkey Virus (MPMV) 11
1.3.2.3 Foamy Virus (FV) 11
1.3.2.4 Hepatitis B virus (HBV) 12
1.4 Hypothesis 13
CHAPTER 2: MATERIAL AND METHODS 15
2.1 Cell culture 15
2.2 Plasmids 15
2.3 Plasmid isolation 15
2.4 Antibodies 17
2.5 HBV genotype D wild-type preparation 17
2.6 Purification Dane particles via Heparin-Affinity Chromatography 18
2.7 Sucrose cushion 18
2.8 In vitro infection 19
2.9 Fractionation of cytoplasmic and nuclear fraction 19
2.10 Quantification of HBV DNA 20
2.11 RNA extraction 21
2.12 mRNA purification 22
2.13 RT-qPCR to quantification of HBV RNAs 22
2.14 RT-PCR to detect HBV spliced RNAs 23
2.15 BCA assay 23
2.16 Western blotting 24
2.17 Northern blot 25
CHAPTER 3: RESULTS 28
3.1 Optimal 3’ Poly(dT)-Adaptor Concentration for Specific Detection of HBV RNA via RT-qPCR: Balancing Sensitivity and Specificity at 20 nM 28
3.2 Enhanced Specificity in HBV RNAs detection via qPCR through mRNA purification 30
3.3 Validation of infected HepG2-NTCP-C4 cells mRNA purification and test RT-qPCR detection of HBV mRNAs in Infected HepG2-NTCP-C4 cells at different time points infection 31
3.4 The temporal kinetics of HBV mRNAs and core protein synthesis 34
3.5 RT-PCR detect HBV spliced RNAs at different time-point infection 37
3.6 The temporal distribution of HBV core Protein during time-point infection 38
CHAPTER 4: DISCUSSIONS 40
CHAPTER 5: FIGURES 48
5.1 Optimization of qPCR 3’Poly(dT)-Adaptor concentration using HepG2-AD38 cDNA and HBV construct for HBV RNA Detection 48
5.2 Validation of HepG2-AD38 cells mRNA purification and verification of no signal in No RT control for qPCR detection of purified HepG2-AD38 mRNA 50
5.3 Validation of infected HepG2-NTCP-C4 cells mRNA purification and RT-qPCR detection of HBV mRNAs in Infected HepG2-NTCP-C4 cells at different time points infection 53
5.4 The temporal kinetics of HBV mRNAs and core protein synthesis 55
5.5 Detection of spliced RNA types appearing at different infection time points via RT-PCR 57
5.6 The temporal distribution of HBV core Protein during time-point infection 59
CHAPTER 6: TABLES 61
6.1 Primer 61
CHAPTER 7: APPENDIX 62
7.1 Life cycle of HBV 62
7.2 Overview of HBV spliced RNA 63
7.3 Plasmid map- pCMV HBV genotype D Precore null 64
REFERENCES 65
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dc.language.isoen-
dc.subjectB型肝炎病毒zh_TW
dc.subject剪接型RNAzh_TW
dc.subject定量反轉錄PCRzh_TW
dc.subjectRNA輸出zh_TW
dc.subjectHBV 信使RNAzh_TW
dc.subjectHBV mRNAen
dc.subjectReal-time quantitative PCRen
dc.subjectHepatitis B virusen
dc.subjectSpliced RNAen
dc.subjectRNA exporten
dc.title在感染中HBV RNA合成的時間動力學zh_TW
dc.titleThe temporal kinetics of HBV RNAs synthesis in infectionen
dc.typeThesis-
dc.date.schoolyear112-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee葉秀慧;陶秘華zh_TW
dc.contributor.oralexamcommitteeShiou-Hwei Yeh ;Mi-Hua Taoen
dc.subject.keywordB型肝炎病毒,HBV 信使RNA,RNA輸出,定量反轉錄PCR,剪接型RNA,zh_TW
dc.subject.keywordHepatitis B virus,HBV mRNA,RNA export,Real-time quantitative PCR,Spliced RNA,en
dc.relation.page71-
dc.identifier.doi10.6342/NTU202402958-
dc.rights.note同意授權(全球公開)-
dc.date.accepted2024-08-02-
dc.contributor.author-college醫學院-
dc.contributor.author-dept微生物學研究所-
dc.date.embargo-lift2026-08-01-
Appears in Collections:微生物學科所

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