進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-0802201212134400
論文名稱(中文) 親和力純化與蛋白質體學研究顯示hnRNPH1、NF45和C14orf166與C型肝炎病毒蛋白鞘有交互作用並影響病毒複製及寄主細胞的增生
論文名稱(英文) An affinity purification-based proteomic approach reveals hnRNPH1, NF45, and C14orf166 as three HCV core-interacting proteins involved in viral replication and cell proliferation in host cells
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 100
學期 1
出版年 101
研究生(中文) 李峻瑋
研究生(英文) Jun-Wei Lee
學號 s5893140
學位類別 博士
語文別 英文
論文頁數 101頁
口試委員 指導教授-王憲威
召集委員-楊孔嘉
口試委員-廖寶琦
口試委員-張定宗
口試委員-陳士隆
口試委員-王錦鈿
中文關鍵字 C型肝炎病毒  核心蛋白  液相層析串聯式質譜儀  異質核醣核酸蛋白H1  核因子  C14orf166  增殖  病毒複製 
英文關鍵字 HCV  HCVc  LC-MS/MS  hnRNPH1  NF45  C14orf166  proliferation  viral replication 
學科別分類
中文摘要 C型肝炎病毒核心蛋白(HCVc)構成病毒核酸蛋白鞘,並可能透過與宿主細胞因子互動以調控其病毒複製及本身之細胞功能,從而導致C型肝炎病毒持續感染及發病。HCVc174是1b基因型HCV(HCV-1b)的成熟型HCVc。利用了N端生物素或C端鈣調蛋白結合肽/蛋白質A標籤的HCVc174親和性純化與一維電泳和串連質譜儀技術(LC-MS/MS),找到了36個極有可能HCVc174與有交互作用的細胞蛋白。藉由沉澱法與共軛焦成像技術,進一步確認異質核醣核酸蛋白H1(hnRNPH1)、核因子(NF45)及C14orf166是新穎的成熟型HCVc174結合寄主蛋白。此外,NF45是透過RNA機制與HCVc174結合。這三種細胞蛋白質在細胞質和細胞核中皆與異位表達的HCVc-1b共位而存,顯示這三種細胞蛋白質在HCVc生成後與自然移位的HCVc174產生空間上的相互作用。然而此共存現象在1b或2a基因型之病毒感染複製時,卻大部分轉移到細胞質,說明活躍的病毒複製會將這些有交互作用的蛋白質侷限在細胞質中。上述結果顯示,hnRNPH1、NF45和C14orf166與HCVc174的空間相互作用,或許可以在急慢性C型肝炎病毒感染期間,發揮控制HCV複製或影響細胞功能的作用。進一步確認了這三種細胞蛋白在細胞存活與C型肝炎病毒複製方面的功能相關性,以查明這三種細胞蛋白成為蛋白質性抗病毒藥物的潛力。透過使之個別降低或過度表達,發現這三種細胞基因是肝細胞長期生存的必要條件,同時也是抑制HCV複製程序的控制因子。本研究中選用C14orf166為對象,進一步研究其與HCVc在HCV複製過程中的交互作用關係。研究發現無論HCVc是否以反式(in trans)存在,C14orf166的過度表達皆可減弱HCV複製;而不論順式(in cis)或反式(in trans)的HCVc表達對於受C14orf166控制的HCV複製程序均無任何顯著的協同或對抗效應。至於HCVc是否僅在C14orf166調控下的HCV複製程序中扮演旁觀輔助因子的角色,或是在生物程序的其他步驟中扮演積極參與因子的角色,則有待進一步研究釐清。本研究結果顯示hnRNPH1、NF45與C14orf166為細胞生存的必要條件,且對於HCV複製過程展現負向控制作用。因此,這三種基因的過度表達可能有助於抑制HCV複製。或者,可針對這三種與HCVc互動的細胞蛋白質,以其功能區段基因產物做為今後研發胜肽型抗病毒藥物的基礎。
英文摘要 The hepatitis C virus core protein (HCVc) forms the viral nucleocapsid and participates in viral persistence and pathogenesis, possibly by interacting with host cellular factors to modulate viral replication and cellular functions. HCVc174 is a mature form of HCVc from HCV genotype 1b (HCV-1b). I identified 36 cellular protein candidates using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography–mass spectrometry/mass spectrometry-based proteomics after affinity purification with HCVc174 that was tagged N-terminally with biotin or C-terminally with calmodulin-binding peptide/protein A. Using pull-down and confocal imaging techniques, I confirmed that heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1), nuclear factor 45 (NF45), and chromosome 14 open reading frame 166 (C14orf166) are novel HCVc174-interacting host proteins. In addition, NF45 interacts with HCVc174 in an RNA-dependent manner. The 3 cellular proteins colocalized with ectopic HCVc-1b in the cytoplasm and nucleus, which indicates that they interact spatially with naturally translocated HCVc174 after HCVc biogenesis. Such colocalization, however, shifted to the cytoplasm with the replicating virus of the 1b or 2a genotype, which suggests that active viral replication confines these interacting proteins to the cytoplasm. These results demonstrate that spatial interactions of hnRNPH1, NF45, and C14orf166 with HCVc174 likely modulate HCV replication or cellular function during acute and chronic HCV infection. To investigate the potential of these 3 cellular proteins as protein-based antiviral drugs, their functional relevance in HCV replication and cell survival was preliminarily determined. Through individual silencing or overexpression, it was found that the 3 cellular genes are required for the prolonged survival of hepatocytes and are negative regulators of the active HCV replication process. C14orf166 was selected to further study the interactive relationship of HCVc in HCV replication. Overexpression of C14orf166 attenuated HCV subgenome replication regardless of whether HCVc was present in trans, and HCVc expression in cis or in trans did not have any significant synergistic or counter effects on C14orf166-modulated HCV replication. Whether HCVc is merely a bystander co-factor participating in the C14orf166-mediated HCV replication process or an active co-factor in other steps of the biological process requires further investigation. Our results show that hnRNPH1, NF45, and C14orf166 are required for cell survival and can negatively regulate HCV replication. Consequently, the overexpression of these 3 genes may be beneficial in limiting HCV replication. Alternatively, truncated gene products of these 3 cellular proteins encoding domains that interact with the HCV core may be useful as potential peptide-based antiviral drugs.
論文目次 中文摘要 I
Abstract III
Acknowledgments V
Table of Contents VI
List of Tables VIII
List of Figures IX
Supporting Information X
Abbreviations XI

1.Introduction
1.1 Viral Life Cycle and Associated Diseases 1
1.2 HCV Core Protein Processing Forms and Their Functional Relevance 2
1.3 HCVc-interacting Host Proteins 3
1.4 Rationale, Approach, and Significance of Findings 5

2.Materials and Methods
2.1 Reagents 7
2.2 Plasmid Constructs 8
2.3 Cell Culture, Transfection, and Infection 9
2.4 Gene Silencing by Lentivirus-mediated RNA Interference 11
2.5 Protein Expression and Western Blot Analysis 12
2.6 Affinity Purification and LC-MS/MS 13
2.7 Affinity Pull-down Assay 16
2.8 Confocal Immunofluorescent Staining 17
2.9 MTS Cell Proliferation Assay 18
2.10 Luciferase Assay for HCV Replication 19
2.11 Establishment of Stable SEAP Reporter Cell Lines Harboring Subgenomic or Full-genomic HCV-1b Con1 20

3.Results
3.1 Expression of HCVc Fusion Proteins 23
3.2 Purification and Identification of Cellular Proteins That Form Complexes with B-HCVc174-CP in HEK293T Cells 23
3.3 Confirmation of the Interaction of HCVc174 with hnRNPH1, NF45, and C14orf166 26
3.4 RNA-dependent Interaction of NF45 with HCVc174 28
3.5 Colocalization of Endogenous hnRNPH1, NF45, and C14orf166 with Ectopically Expressed HCVc from HCV-1b 28
3.6 Colocalization of Endogenous hnRNPH1, NF45, and C14orf166 with Endogenous HCVc from HCV-1b and HCV-2a 29
3.7 Inhibition of Huh7 Cells Proliferation by hnRNPH1, NF45, or C14orf166 Knockdown 31
3.8 Effects of hnRNPH1, NF45, or C14orf166 Overexpression or Knockdown on HCV Subgenome Replication in the Absence of HCVc 31
3.9 Effects of C14orf166 Overexpression or Knockdown on HCV Replication in the Presence or Absence of HCVc in cis or trans 32

4.Discussion
4.1 Summary Novel Findings 35
4.2 Critical Aspects of the Interaction of HCVc with hnRNPH1, NF45, and C14orf166 35
4.3 Possible New Functions of HCVc 36
4.4 Relationship of HCVc and miRNA Biogenesis 38
4.5 Limitations of the Study 38
4.6 Conclusions 40

5.References 42

Tables 54

Figures 55

6.Supporting information 76

7.Curriculum Vitae 101

參考文獻 1. Blackard, J. T.; Kemmer, N.; Sherman, K. E., Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences. Hepatology 2006, 44, (1), 15-22.
2. Sansonno, D.; Dammacco, F., Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis 2005, 5, (4), 227-36.
3. Ai, L. S.; Lee, Y. W.; Chen, S. S. L., Characterization of hepatitis C virus core protein multimerization and membrane envelopment: revelation of a cascade of core-membrane interactions. J Virol 2009, 83, (19), 9923-39.
4. Boonstra, A.; van der Laan, L. J.; Vanwolleghem, T.; Janssen, H. L., Experimental models for hepatitis C viral infection. Hepatology 2009, 50, (5), 1646-55.
5. Boni, S.; Lavergne, J. P.; Boulant, S.; Cahour, A., Hepatitis C virus core protein acts as a trans-modulating factor on internal translation initiation of the viral RNA. J Biol Chem 2005, 280, (18), 17737-48.
6. Kang, S. M.; Choi, J. K.; Kim, S. J.; Kim, J. H.; Ahn, D. G.; Oh, J. W., Regulation of hepatitis C virus replication by the core protein through its interaction with viral RNA polymerase. Biochem Biophys Res Commun 2009, 386, (1), 55-9.
7. Ait-Goughoulte, M.; Banerjee, A.; Meyer, K.; Mazumdar, B.; Saito, K.; Ray, R. B.; Ray, R., Hepatitis C virus core protein interacts with fibrinogen-beta and attenuates cytokine stimulated acute-phase response. Hepatology 2010, 51, (5), 1505-13.
8. Kountouras, J.; Zavos, C.; Chatzopoulos, D., Apoptosis in hepatitis C. J Viral Hepat 2003, 10, (5), 335-42.
9. Mogensen, M. M.; Malik, A.; Piel, M.; Bouckson-Castaing, V.; Bornens, M., Microtubule minus-end anchorage at centrosomal and non-centrosomal sites: the role of ninein. J Cell Sci 2000, 113 (Pt 17), 3013-23.
10. Waggoner, S. N.; Hall, C. H. T.; Hahn, Y. S., HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. J Leukoc Biol 2007, 82, (6), 1407-19.
11. Simmonds, P.; Bukh, J.; Combet, C.; Deleage, G.; Enomoto, N.; Feinstone, S.; Halfon, P.; Inchauspe, G.; Kuiken, C.; Maertens, G.; Mizokami, M.; Murphy, D. G.; Okamoto, H.; Pawlotsky, J. M.; Penin, F.; Sablon, E.; Shin, I. T.; Stuyver, L. J.; Thiel, H. J.; Viazov, S.; Weiner, A. J.; Widell, A., Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005, 42, (4), 962-73.
12. Tanaka, Y.; Hanada, K.; Mizokami, M.; Yeo, A. E.; Shih, J. W.; Gojobori, T.; Alter, H. J., Inaugural Article: A comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades. Proc Natl Acad Sci U S A 2002, 99, (24), 15584-9.
13. Kato, T.; Date, T.; Murayama, A.; Morikawa, K.; Akazawa, D.; Wakita, T., Cell culture and infection system for hepatitis C virus. Nat Protoc 2006, 1, (5), 2334-9.
14. Lo, S. Y.; Masiarz, F.; Hwang, S. B.; Lai, M. M.; Ou, J. H., Differential subcellular localization of hepatitis C virus core gene products. Virology 1995, 213, (2), 455-61.
15. Suzuki, R.; Sakamoto, S.; Tsutsumi, T.; Rikimaru, A.; Tanaka, K.; Shimoike, T.; Moriishi, K.; Iwasaki, T.; Mizumoto, K.; Matsuura, Y.; Miyamura, T.; Suzuki, T., Molecular determinants for subcellular localization of hepatitis C virus core protein. J Virol 2005, 79, (2), 1271-81.
16. Yasui, K.; Wakita, T.; Tsukiyama-Kohara, K.; Funahashi, S. I.; Ichikawa, M.; Kajita, T.; Moradpour, D.; Wands, J. R.; Kohara, M., The native form and maturation process of hepatitis C virus core protein. J Virol 1998, 72, (7), 6048-55.
17. McLauchlan, J., Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J Viral Hepat 2000, 7, (1), 2-14.
18. Cristofari, G.; Ivanyi-Nagy, R.; Gabus, C.; Boulant, S.; Lavergne, J. P.; Penin, F.; Darlix, J. L., The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro. Nucleic Acids Res 2004, 32, (8), 2623-31.
19. Klein, K. C.; Dellos, S. R.; Lingappa, J. R., Identification of residues in the hepatitis C virus core protein that are critical for capsid assembly in a cell-free system. J Virol 2005, 79, (11), 6814-26.
20. Majeau, N.; Gagne, V.; Boivin, A.; Bolduc, M.; Majeau, J. A.; Ouellet, D.; Leclerc, D., The N-terminal half of the core protein of hepatitis C virus is sufficient for nucleocapsid formation. J Gen Virol 2004, 85, (Pt 4), 971-81.
21. Duvignaud, J. B.; Savard, C.; Fromentin, R.; Majeau, N.; Leclerc, D.; Gagne, S. M., Structure and dynamics of the N-terminal half of hepatitis C virus core protein: an intrinsically unstructured protein. Biochem Biophys Res Commun 2009, 378, (1), 27-31.
22. Maillard, P.; Lavergne, J. P.; Siberil, S.; Faure, G.; Roohvand, F.; Petres, S.; Teillaud, J. L.; Budkowska, A., Fc gamma receptor-like activity of hepatitis C virus core protein. J Biol Chem 2004, 279, (4), 2430-7.
23. Namboodiri, A. M.; Budkowska, A.; Nietert, P. J.; Pandey, J. P., Fc gamma receptor-like hepatitis C virus core protein binds differentially to IgG of discordant Fc (GM) genotypes. Mol Immunol 2007, 44, (15), 3805-8.
24. Yeh, C. T.; Lo, S. Y.; Dai, D. I.; Tang, J. H.; Chu, C. M.; Liaw, Y. F., Amino acid substitutions in codons 9-11 of hepatitis C virus core protein lead to the synthesis of a short core protein product. J Gastroenterol Hepatol 2000, 15, (2), 182-91.
25. Ruster, B.; Zeuzem, S.; Krump-Konvalinkova, V.; Berg, T.; Jonas, S.; Severin, K.; Roth, W. K., Comparative sequence analysis of the core- and NS5-region of hepatitis C virus from tumor and adjacent non-tumor tissue. J Med Virol 2001, 63, (2), 128-34.
26. Shirakura, M.; Murakami, K.; Ichimura, T.; Suzuki, R.; Shimoji, T.; Fukuda, K.; Abe, K.; Sato, S.; Fukasawa, M.; Yamakawa, Y.; Nishijima, M.; Moriishi, K.; Matsuura, Y.; Wakita, T.; Suzuki, T.; Howley, P. M.; Miyamura, T.; Shoji, I., E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein. J Virol 2007, 81, (3), 1174-85.
27. Suzuki, R.; Tamura, K.; Li, J.; Ishii, K.; Matsuura, Y.; Miyamura, T.; Suzuki, T., Ubiquitin-mediated degradation of hepatitis C virus core protein is regulated by processing at its carboxyl terminus. Virology 2001, 280, (2), 301-9.
28. Kang, S. M.; Shin, M. J.; Kim, J. H.; Oh, J. W., Proteomic profiling of cellular proteins interacting with the hepatitis C virus core protein. Proteomics 2005, 5, (8), 2227-37.
29. Kang, S. M.; Kim, S. J.; Kim, J. H.; Lee, W.; Kim, G. W.; Lee, K. H.; Choi, K. Y.; Oh, J. W., Interaction of hepatitis C virus core protein with Hsp60 triggers the production of reactive oxygen species and enhances TNF-alpha-mediated apoptosis. Cancer Lett 2009, 279, (2), 230-7.
30. McGivern, D. R.; Lemon, S. M., Tumor suppressors, chromosomal instability, and hepatitis C virus-associated liver cancer. Annual review of pathology 2009, 4, 399-415.
31. Goh, P. Y.; Tan, Y. J.; Lim, S. P.; Tan, Y. H.; Lim, S. G.; Fuller-Pace, F.; Hong, W., Cellular RNA helicase p68 relocalization and interaction with the hepatitis C virus (HCV) NS5B protein and the potential role of p68 in HCV RNA replication. J Virol 2004, 78, (10), 5288-98.
32. Matto, M.; Rice, C. M.; Aroeti, B.; Glenn, J. S., Hepatitis C virus core protein associates with detergent-resistant membranes distinct from classical plasma membrane rafts. J Virol 2004, 78, (21), 12047-53.
33. Okamoto, K.; Mori, Y.; Komoda, Y.; Okamoto, T.; Okochi, M.; Takeda, M.; Suzuki, T.; Moriishi, K.; Matsuura, Y., Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation. J Virol 2008, 82, (17), 8349-61.
34. Drakas, R.; Prisco, M.; Baserga, R., A modified tandem affinity purification tag technique for the purification of protein complexes in mammalian cells. Proteomics 2005, 5, (1), 132-7.
35. Beard, M. R.; Abell, G.; Honda, M.; Carroll, A.; Gartland, M.; Clarke, B.; Suzuki, K.; Lanford, R.; Sangar, D. V.; Lemon, S. M., An infectious molecular clone of a Japanese genotype 1b hepatitis C virus. Hepatology 1999, 30, (1), 316-24.
36. Kato, T.; Matsumura, T.; Heller, T.; Saito, S.; Sapp, R. K.; Murthy, K.; Wakita, T.; Liang, T. J., Production of infectious hepatitis C virus of various genotypes in cell cultures. J Virol 2007, 81, (9), 4405-11.
37. Blight, K. J.; McKeating, J. A.; Rice, C. M., Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J Virol 2002, 76, (24), 13001-14.
38. Cristea, I. M.; Williams, R.; Chait, B. T.; Rout, M. P., Fluorescent proteins as proteomic probes. Mol Cell Proteomics 2005, 4, (12), 1933-41.
39. Chang, Y. H.; Wu, C. C.; Chang, K. P.; Yu, J. S.; Chang, Y. C.; Liao, P. C., Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma. J Proteome Res 2009, 8, (12), 5465-74.
40. Perkins, D. N.; Pappin, D. J.; Creasy, D. M.; Cottrell, J. S., Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 1999, 20, (18), 3551-67.
41. Li, K.; Prow, T.; Lemon, S. M.; Beard, M. R., Cellular response to conditional expression of hepatitis C virus core protein in Huh7 cultured human hepatoma cells. Hepatology 2002, 35, (5), 1237-46.
42. Lohmann, V.; Hoffmann, S.; Herian, U.; Penin, F.; Bartenschlager, R., Viral and cellular determinants of hepatitis C virus RNA replication in cell culture. J Virol 2003, 77, (5), 3007-19.
43. Sun, H.-Y.; Ou, N.-Y.; Wang, S.-W.; Liu, W.-C.; Cheng, T.-F.; Shr, S.-J.; Sun, K.-T.; Chang, T.-T.; Young, K.-C., Novel Nucleotide and Amino Acid Covariation between the 5′UTR and the NS2/NS3 Proteins of Hepatitis C Virus: Bioinformatic and Functional Analyses. PLoS One 2011, 6, (9), e25530.
44. Lee, J. C.; Chang, C. F.; Chi, Y. H.; Hwang, D. R.; Hsu, J. T., A reporter-based assay for identifying hepatitis C virus inhibitors based on subgenomic replicon cells. J Virol Methods 2004, 116, (1), 27-33.
45. Fang, C.; Yi, Z.; Liu, F.; Lan, S.; Wang, J.; Lu, H.; Yang, P.; Yuan, Z., Proteome analysis of human liver carcinoma Huh7 cells harboring hepatitis C virus subgenomic replicon. Proteomics 2006, 6, (2), 519-27.
46. Jablonski, J. A.; Caputi, M., Role of cellular RNA processing factors in human immunodeficiency virus type 1 mRNA metabolism, replication, and infectivity. J Virol 2009, 83, (2), 981-92.
47. Isken, O.; Baroth, M.; Grassmann, C. W.; Weinlich, S.; Ostareck, D. H.; Ostareck-Lederer, A.; Behrens, S. E., Nuclear factors are involved in hepatitis C virus RNA replication. RNA 2007, 13, (10), 1675-92.
48. Merrill, M. K.; Gromeier, M., The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site. J Virol 2006, 80, (14), 6936-42.
49. Sakamoto, S.; Aoki, K.; Higuchi, T.; Todaka, H.; Morisawa, K.; Tamaki, N.; Hatano, E.; Fukushima, A.; Taniguchi, T.; Agata, Y., The NF90-NF45 complex functions as a negative regulator in the microRNA processing pathway. Mol Cell Biol 2009, 29, (13), 3754-69.
50. Zhao, G.; Shi, L.; Qiu, D.; Hu, H.; Kao, P. N., NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function. Exp Cell Res 2005, 305, (2), 312-23.
51. Cui, Y.; Wu, J.; Zong, M.; Song, G.; Jia, Q.; Jiang, J.; Han, J., Proteomic profiling in pancreatic cancer with and without lymph node metastasis. Int J Cancer 2009, 124, (7), 1614-21.
52. Howng, S. L.; Hsu, H. C.; Cheng, T. S.; Lee, Y. L.; Chang, L. K.; Lu, P. J.; Hong, Y. R., A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by GSK3beta and is highly expressed in brain tumors. FEBS Lett 2004, 566, (1-3), 162-8.
53. Ariumi, Y.; Kuroki, M.; Abe, K.; Dansako, H.; Ikeda, M.; Wakita, T.; Kato, N., DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol 2007, 81, (24), 13922-6.
54. Parent, R.; Qu, X.; Petit, M. A.; Beretta, L., The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity. Hepatology 2009, 49, (6), 1798-809.
55. Roohvand, F.; Maillard, P.; Lavergne, J. P.; Boulant, S.; Walic, M.; Andreo, U.; Goueslain, L.; Helle, F.; Mallet, A.; McLauchlan, J.; Budkowska, A., Initiation of hepatitis C virus infection requires the dynamic microtubule network: role of the viral nucleocapsid protein. J Biol Chem 2009, 284, (20), 13778-91.
56. Rocak, S.; Linder, P., DEAD-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol 2004, 5, (3), 232-41.
57. Lai, C. K.; Jeng, K. S.; Machida, K.; Lai, M. M., Hepatitis C virus egress and release depend on endosomal trafficking of core protein. J Virol 2010, 84, (21), 11590-8.
58. Shavinskaya, A.; Boulant, S.; Penin, F.; McLauchlan, J.; Bartenschlager, R., The lipid droplet binding domain of hepatitis C virus core protein is a major determinant for efficient virus assembly. J Biol Chem 2007, 282, (51), 37158-69.
59. Zhang, J.; Yamada, O.; Yoshida, H.; Iwai, T.; Araki, H., Autogenous translational inhibition of core protein: implication for switch from translation to RNA replication in hepatitis C virus. Virology 2002, 293, (1), 141-50.
60. Graber, T. E.; Baird, S. D.; Kao, P. N.; Mathews, M. B.; Holcik, M., NF45 functions as an IRES trans-acting factor that is required for translation of cIAP1 during the unfolded protein response. Cell Death Differ 2010, 17, (4), 719-29.
61. Huang, Y. S.; Dai, Y.; Yu, X. F.; Bao, S. Y.; Yin, Y. B.; Tang, M.; Hu, C. X., Microarray analysis of microRNA expression in hepatocellular carcinoma and non-tumorous tissues without viral hepatitis. J Gastroenterol Hepatol 2008, 23, (1), 87-94.
62. Varnholt, H.; Drebber, U.; Schulze, F.; Wedemeyer, I.; Schirmacher, P.; Dienes, H. P.; Odenthal, M., MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology 2008, 47, (4), 1223-32.
63. Volk, N.; Shomron, N., Versatility of MicroRNA biogenesis. PLoS One 2011, 6, (5), e19391.
64. Bemmo, A.; Dias, C.; Rose, A. A.; Russo, C.; Siegel, P.; Majewski, J., Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities. PLoS One 2010, 5, (8), e11981.
65. Zhu, H.; Cui, Y.; Xie, J.; Chen, L.; Chen, X.; Guo, X.; Zhu, Y.; Wang, X.; Tong, J.; Zhou, Z.; Jia, Y.; Lue, Y. H.; Hikim, A. S.; Wang, C.; Swerdloff, R. S.; Sha, J., Proteomic analysis of testis biopsies in men treated with transient scrotal hyperthermia reveals the potential targets for contraceptive development. Proteomics 2010, 10, (19), 3480-93.
66. Guan, D. Y.; Altan-Bonnet, N.; Parrott, A. M.; Arrigo, C. J.; Li, Q.; Khaleduzzaman, M.; Li, H.; Lee, C. G.; Pe'ery, T.; Mathews, M. B., Nuclear factor 45 (NF45) is a regulatory subunit of complexes with NF90/110 involved in mitotic control. Mol Cell Biol 2008, 28, (14), 4629-41.
67. White, M. K.; Johnson, E. M.; Khalili, K., Multiple roles for Puralpha in cellular and viral regulation. Cell Cycle 2009, 8, (3), 1-7.
68. Kanai, Y.; Dohmae, N.; Hirokawa, N., Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 2004, 43, (4), 513-25.
69. Sung, T. L.; Rice, A. P., miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1. PLoS Pathog 2009, 5, (1), e1000263.
70. Gregory, R. I.; Yan, K. P.; Amuthan, G.; Chendrimada, T.; Doratotaj, B.; Cooch, N.; Shiekhattar, R., The Microprocessor complex mediates the genesis of microRNAs. Nature 2004, 432, (7014), 235-40.
71. Matsumoto, M.; Hsieh, T. Y.; Zhu, N.; VanArsdale, T.; Hwang, S. B.; Jeng, K. S.; Gorbalenya, A. E.; Lo, S. Y.; Ou, J. H.; Ware, C. F.; Lai, M. M., Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor. J Virol 1997, 71, (2), 1301-9.
72. Hsieh, T. Y.; Matsumoto, M.; Chou, H. C.; Schneider, R.; Hwang, S. B.; Lee, A. S.; Lai, M. M., Hepatitis C virus core protein interacts with heterogeneous nuclear ribonucleoprotein K. J Biol Chem 1998, 273, (28), 17651-9.
73. Ariumi, Y.; Kuroki, M.; Abe, K.; Dansako, H.; Ikeda, M.; Wakita, T.; Kato, N., DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol 2007, 81, (24), 13922-6.
74. Owsianka, A. M.; Patel, A. H., Hepatitis C virus core protein interacts with a human DEAD box protein DDX3. Virology 1999, 257, (2), 330-40.
75. de Chassey, B.; Navratil, V.; Tafforeau, L.; Hiet, M. S.; Aublin-Gex, A.; Agaugue, S.; Meiffren, G.; Pradezynski, F.; Faria, B. F.; Chantier, T.; Le Breton, M.; Pellet, J.; Davoust, N.; Mangeot, P. E.; Chaboud, A.; Penin, F.; Jacob, Y.; Vidalain, P. O.; Vidal, M.; Andre, P.; Rabourdin-Combe, C.; Lotteau, V., Hepatitis C virus infection protein network. Mol Syst Biol 2008, 4, 230.
76. Angus, A. G.; Dalrymple, D.; Boulant, S.; McGivern, D. R.; Clayton, R. F.; Scott, M. J.; Adair, R.; Graham, S.; Owsianka, A. M.; Targett-Adams, P.; Li, K.; Wakita, T.; McLauchlan, J.; Lemon, S. M.; Patel, A. H., Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein. J Gen Virol 2010, 91, (Pt 1), 122-32.
77. Lee, J. W.; Liao, P. C.; Young, K. C.; Chang, C. L.; Chen, S. S.; Chang, T. T.; Lai, M. D.; Wang, S. W., Identification of hnRNPH1, NF45, and C14orf166 as novel host interacting partners of the mature hepatitis C virus core protein. J Proteome Res 2011, 10, (10), 4522-34.
78. You, L. R.; Chen, C. M.; Yeh, T. S.; Tsai, T. Y.; Mai, R. T.; Lin, C. H.; Lee, Y. H., Hepatitis C virus core protein interacts with cellular putative RNA helicase. J Virol 1999, 73, (4), 2841-53.
79. Aoki, H.; Hayashi, J.; Moriyama, M.; Arakawa, Y.; Hino, O., Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1. J Virol 2000, 74, (4), 1736-41.
80. Lee, S. K.; Park, S. O.; Joe, C. O.; Kim, Y. S., Interaction of HCV core protein with 14-3-3epsilon protein releases Bax to activate apoptosis. Biochem Biophys Res Commun 2007, 352, (3), 756-62.
81. Chen, Y. R.; Chen, T. Y.; Zhang, S. L.; Lin, S. M.; Zhao, Y. R.; Ye, F.; Zhang, X.; Shi, L.; Dang, S. S.; Liu, M., Identification of a novel protein binding to hepatitis C virus core protein. J Gastroenterol Hepatol 2009, 24, (7), 1300-4.
82. Tsutsumi, T.; Matsuda, M.; Aizaki, H.; Moriya, K.; Miyoshi, H.; Fujie, H.; Shintani, Y.; Yotsuyanagi, H.; Miyamura, T.; Suzuki, T.; Koike, K., Proteomics analysis of mitochondrial proteins reveals overexpression of a mitochondrial protein chaperon, prohibitin, in cells expressing hepatitis C virus core protein. Hepatology 2009, 50, (2), 378-86.

論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2017-02-16起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw