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研究生:李佳穎
研究生(外文):Jia-Ying Lee
論文名稱:NORPEG基因高度表現於C型肝炎病毒蛋白質表現細胞之研究
論文名稱(外文):Up-regulation of NORPEG Gene in Hepatitis C Virus Proteins Expressing Cells
指導教授:張明富
指導教授(外文):Ming-Fu Chang
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生物化學暨分子生物學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:58
中文關鍵詞:C型肝炎病毒肝癌
外文關鍵詞:p53NORPEGhepatitis C virushepatocellular carcinoma
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肝細胞癌(HCC)是世界上最普遍的癌症之一,儘管在最近幾年中陸續發展了新的治療方式,不過肝癌之預後效果還是不太理想。造成肝癌之主要因素為由B型肝炎病毒(HBV)以及C型肝炎病毒(HCV)所引起之慢性肝炎,以及其他不同之致癌物包括了黃麴毒素等。本篇論文主要是在探討C型肝炎病毒以及肝癌之間的關係。
最近研究指出受到C型肝炎病毒感染之B細胞淋巴癌其p53基因會出現高度之突變情形。為了瞭解與肝癌生成有關之分子機制,本論文利用人類肝癌細胞株Huh7以及經繼代培養後含有HCV subgenomic replicon之Huh7細胞株,來觀察其p53基因之變異情形。在分析過Huh7以及第12、22、47、80和132代HCV Replicon細胞之p53基因後,我們觀察到了兩個點突變的位置。其一為第411組核苷酸對C•G突變為T•A,該突變沒有造成該位置胺基酸的改變 (Leu)。另一個為第793組核苷酸對A•T突變為G•C,該突變造成了p53蛋白質第220個胺基酸Tyr轉變為Cys。而於其他含有HCV subgenomic replicon的Huh7細胞中並沒有觀察到p53基因上更多的突變。
另外在本實驗室DNA微陣列分析的結果中,發現一個未知功能的NORPEG基因,其表現於第33代HCV Replicon細胞中有提升的現象。同時在之前的研究中亦指出該基因於HCC中的表現也有提升的情形。經由即時定量聚合酶連鎖反應的分析得到該基因在第12及22代HCV Replicon細胞中的表現出現了增加的現象。接著利用Western blot analysis探討了NORPEG蛋白質於不同細胞株中的表現情形,發現其於肝癌細胞株中(Huh7,HepG2)之表現較子宮頸癌細胞株(HeLa)為多,並且於穩定表現HCV核心蛋白質之HeLa細胞(Core-6, Core-13)中的表現也較HeLa細胞為多。
由以上實驗顯示,與HCV非結構性蛋白質相較之下,核心蛋白質對於NORPEG蛋白質之表現產生了較多的影響。HCV核心蛋白質以及非結構性蛋白質如何調控NORPEG基因,以及NOPPEG蛋白質可能參與肝癌生成之分子機制仍待進一步之研究來闡明。
Primary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Despite the development of novel therapeutic methods in recent years, prognosis of advanced HCC is still poor. Major risk factors for HCC are chronic hepatitis resulting from infection with hepatitis B or C virus, and exposure to various exogenous carcinogens including aflatoxin B1. In this study, the relationship between HCV and HCC is under investigation.
Recent studies identified hypermutation of p53 gene in HCV-infected B cell lymphoma. To understand the molecular mechanisms of HCV involved in the hepatocarcinogenesis, mutation status of p53 in HCV replicon-containing cell line and the parental Huh7 cells were analyzed. Two mutations were found in the p53 gene of Huh7 and HCV replicon cells continually passaged for 12, 22, 47, 80 and 132 generations. C to T mutation at nucleotide 411 resulted in a silent mutation, whereas the A to G mutation at nucleotide 793 caused a tyrosine to cysteine mutation at amino acid residue 220. No additional mutations were observed in the HCV replicon cell lines.
On the other hand, by performing DNA microarray analysis, our laboratory have previously identified a novel gene NORPEG that was up-regulated in the HCV replicon-containing Huh7 cell line (the 33rd passage). This result was confirmed by real-time PCR analysis of HCV replicon cell lines (the 12th and the 22nd passages). NORPEG gene was recently reported to be up-regulated in HCC, but its function is still not fully understood. Antibodies specific to NORPEG protein were generated. Western blot analysis demonstrated that the expression levels of NORPEG protein were higher in the human hepatoma cell lines Huh7 and HepG2 than in non-hepatic HeLa cells. In addition, the expression level of NORPEG protein was also higher in HCV core protein-expressing HeLa cells (Core-6 and Core-13) when compared to the parental HeLa cells. These results suggest that NORPEG may have a role involved in the pathogenesis of the core protein and the hepatocarcinigenesis of HCV.
中文摘要……………………...………Ⅰ
英文摘要……………………………… Ⅱ
縮寫表…………………………..…… Ⅲ
緒論…………………………………..…1
實驗材料來源………………………….12
實驗方法……………………………… 15
實驗結果……………….………………28
討論…….………………………………32
圖表…………….………………………36
參考文獻……………………………….50
Asabe, S. I., Tanji, Y., Satoh, S., Kaneko, T., Kimura, K., and Shimotohno, K. (1997). The N-terminal region of hepatitis C virus-encoded NS5A is important for NS4A-dependent phosphorylation. J. Virol. 71, 790-796.

Bartenschlager, R., Ahlborn-Laake, L., Mous, J., and Jacobson, H. (1993). Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J. Virol.67: 3835-44.

Bartenschlager, R. and Lohmann, V. (2000). Replication of hepatitis C virus. J. Gen. Virol. 81: 1631-48.

Bartenschlager, R. and Lohmann, V. (2001). Novel cell culture systems for the hepatitis C virus. Antiviral Research 52(1): Pages 1-17.

Bartenschlager, R. (2002). Hepatitis C virus replicons: potential role for drug development. Nat. Rev. Drug. Discov. 1, 911-6.

Behrens, S. E., Tomei, L., and De Francesco, R. (1996). Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J. 15, 12-22.

Blight, K. J., Kolykhalov, A. A., and Rice, C. M. (2000). Efficient initiation of HCV RNA replication in cell culture. Science 290, 1972-1974.

Block, T. M., Mentha, A. S., Fimmel, C. J., Jordan, R. (2003). Molecular viral oncology of hepatocellular carcinoma. Oncogene 22: 5093-107.

Bukh, J., Miller, R. H., Kew, M. C., Purcell, R. H. (1993). Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma. Proc. Natl. Acad. Sci .U S A 90: 1848-51.

Carrère-Kremer, S., Montpellier-Pala, C., Cocquerel, L., Wychowski, C., Penin, F., and Dubuisson, J. (2002). Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. J. Virol. 76, 3720-3730.


Chang, J., Yang, S. H., Cho, Y. G., Hwang, S. B., Hahn, Y. S., and Sung, Y. C. (1998). Hepatitis C virus core from two different genotypes has an oncogenic potential but is not sufficient for transforming primary rat embryo fibroblasts in cooperation with the H-ras oncogene. J. Virol. 72, 3060-3065.

Chen, C. M., You, L. R., Hwang, L. H., and Lee, Y. H. (1997) Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor. J. Virol. 71, 9417-9426.

Chen, J. -G. et al. (1998). Population-based cancer survival in Qidong, People’s Republic of China. IARC Sci. Publ. 145, 27-35.

Cheng, J. C., Chang, M. F., and Chang, S. C. (1999). Specific interaction between the hepatitis C virus NS5B RNA polymerase and the 3’ end of the viral RNA. J. Virol. 73, 7044-7049.

Choo, Q. L., Kuo, G., Weiner, A. J., Overby, L. R., Bradley, D. W., Houghton, M. (1989). Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359-62.

Choo, Q. L., Richman, K. H., Han, J. H., Berger, K., Lee, C., Dong, C., Gallegos, C., Coit, D., Medina-Selby, A., Barr, P. J., Weiner, A. J., Bradley, D. W., Kuo, G., and Houghton, M. (1991). Genetic Organization and diversity of the hepatitis C virus. Proc. Natl. Acad. Sci. USA 88, 2451-2455.

Deleersnyder, V., Pillez, A., Wychowski, C., Blight, K., Xu, J., Hahn, Y. S., Rice, C. M., and Dubuisson, J. (1997). Formation of native hepatitis C virus glycoprotein complexes. J. Virol. 71, 697-704.

Frese, M., Pietschmann, T., Moradpour, D., Haller, O., and Bartenschlager, R. (2001). Interferon-α inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway. J. Gen. Virol. 82, 723-733.

Friebe, P., and Bartenschlager, R. (2002). Genetic analysis of sequences in the 3’ nontranslated region of hepatitis C virus that are important for RNA replication. J. Virol. 76, 5326-5338.


Gosh, A. K., Steele, R., Meyer, K., Ray, R., and Ray, R. B. (1999). Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. J. Gen. Virol. 80, 1179-1183.

Grakoui, A., McCourt, D. W., Wychowski, C., Feinstone, S. M., and Rice, C. M. (1993b). Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. J. Virol. 67, 2832-2843.

Hayashi, J., Aoki, H., Arakawa, Y., Hino, O. (1999). Hepatitis C virus and hepatocarcinogenesis. Intervirology 42: 205-10.

Hijikata, M., Mizushima, H., Akagi, T., Mori, S., Kakiuchi, N., Kato, N., Tanaka, T., Kimura, K., and Shimotohno, K. (1993a). Two distinct proteinase activities required for the processing of a putative non-structural precursor protein of hepatitis C virus. J. Virol. 67, 4665-4675.

Hsu, H. C., Tseng, H. J., Lai, P. L., Lee, P. H., and Peng, S. Y. (1993). Expression of p53 gene in 184 unifocal hepatocellular carcinomas: association with tumor growth and invasiveness. Cancer Res., 53, 4691-4694.

Hu, K. H., Vierling, J. M., and Redeker, A.G. (2001). Viral, host, and interferon-related factors modulating the effect of interferon therapy for hepatitis C virus infection. J. Viral Hepat. 8, 1-18.

Ide, Y., Tanimoto, A., Sasaguri, Y., and Padmanabhan, R. (1997). Hepatitis C virus NS5A protein is phophorylated in vitro by a stably bound protein kinase from HeLa cells and by cAMP-dependent protein kinase A-alpha catalytic subunit. Gene 201, 151-158.

Jemel, A. et al. (2003). Cancer statistics 2003. CA Cancer J. Clin. 53, 5-26.

Kaneko, T., Tanji, Y., Satoh, S., Hijikata, M., Asabe, S., Kimura, K., and Shimotohno, K. (1994). Production of two phosphoproteins from the NS5A region of hepatitis C viral genome. Biochem. Biophys. Res. Commun. 205, 320-326.



Kao, C. F., Chen, S. Y., Chen, J. Y., Wu Lee, Y. H. (2004). Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein. Oncogene 23: 2472-83.

Kato, N., Hijikata, M., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S., Sugimura, T., and Shimotohno, K. (1990). Molecular Cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc. Natl. Acad. Sci. USA 87, 9524-9528.

Kato, J., Kato, N., Yoshida, H., Ono-Nita, S. K., Shiratori, Y., and Omata, M. (2002). Hepatitis C virus NS4A and NS4B proteins suppress translation in vivo. J. Med.Virol. 66, 187-199.

Kittlesen, D. J. F., Chianese-Bullock, K. A. F., Yao, Z. Q. F., Braciale T. J. F., and Han Y. S. (2000). Interaction between complement receptor gClqR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. J. Clin. Invest., 106, 1239-1249.

Kensler, T. W., Qian, G. S., Chen, J. G., Groopman, J. D. (2003). Translational strategies for cancer prevention in liver. Nat. Rev. Cancer. 3: 321-9.

Kolykhalov, A. A., Feinstone, S. M., and Rice, C.M. (1996). Identification of a highly conserved sequence element at the 3’ terminus of hepatitis C virus genome RNA. J.Virol. 70, 3363-3371.

Kolykhalov, A. A., Mihalik, K., Feistone, S. M., and Rice, C. M. (2000). Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3’ nontranslated-region are essential for virus replication in vivo. J. Virol. 75, 4614-4624.

Krieger, N., Lohmann, V., and Bartensclager, R. (2001). Enhancement of hepatitis C virus RNA replication by cell culture-adaptive mutations. J. Virol. 75, 4614-4624.

Kutty, R. K., Kutty, G., Samuel, W., Duncan, T., Bridges, C. C., El-Sherbeeny, A., Nagineni, C. N., Smith, S. B., Wiggert, B. (2001). Molecular characterization and developmental expression of NORPEG, a novel gene induced by retinoic acid. J. Biol. Chem. 276: 2831-40.

Lan, K. H., Sheu, M. L., Hwang, S. J., Yen, S. H., Chen, S. Y., Wu, J. C., Wang, Y. J., Kato, N., Omata, M., Chang, F. Y., Lee, S. D. (2002). HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene 21: 4801-11.

Lerat, H., Honda, M., Beard, M. R., Loesch, K., Sun, J., Yang, Y., Okuda, M., Gosert, R., Xiao, S. Y., Weinman, S. A., and Lemon, S. M. (2002). Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 122, 352-365.

Li, L.and Rao, K. (eds.) Cancer Incidence and Mortality in Cities and Countries of P. R. China 1988-1992 (China Medical Science and Technology Press, 2001).

Lohmann, V., Körner, F., Herian, U., and Bartenschlager, R. (1997). Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity. J. Virol. 71, 8416-8428.

Lohmann, V., Körner, F., Koch, J. O., Herian, U., Theilmann, L., and Bartenschlager, R. (1999). Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285, 110-113.

Lohmann, V., Körner, F., Dobierzewska, A., and Bartenschalager, R. (2001). Mutations in hepatitis C virus RNAs conferring cell culture adaptation. J. Virol. 75, 1437-1449.

Lohmann, V., Hoffmann, S., Herian, U., Penin, F., and Bartenschalger, R. (2003). Viral and cellular determinants of hepatitis C virus RNA replication in cell culture. J. Virol. 77, 3007-3019.

Lukavsky, P. J., Otto, G. A., Lancaster, A. M., Sarnow, P., and Puglisi, J.D. (2000). Structures of rwo RNA domains essential for hepatitis C virus internal ribosome entry site function. Nat. Struct. Biol. 12, 1105-1110.

Machida, K., Cheng, K. T., Sung, V. M., Shimodaira, S., Lindsay, K. L., Levine, A. M., Lai, M. Y., Lai, M. M. (2004). Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc. Natl. Acad. Sci. U S A 101: 4262-7.

Majumder, M., Ghosh, A. K., Steele, R., Ray, R., Ray, R. B. (2001). Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. J. Virol .75: 1401-7.

McLauchlan, J. (2000). Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J. Viral Hepat. 7, 2-14.

Mercer, D. F., Schiller, D. E., Elliott, J. F., Douglas, D. N., Hao, C., Rinfret, A., Addison, W. R., Fischer, K. P., Churchill, T. A., Lakey, J. R. T., Tyrrel, D. L. J., and Kneteman, N. M. (2001). Hepatitis C virus replication in mice with chimeric human livers. Nat. Med. 7, 927-933.

Merican, I. et al. (2000) Chronic hepatitis B virus infection in Asian countries. J. Gastroenterol. Hepatol. 15, 1356-1361.

Moradpour, D., Brass, V., Gosert, R., Wolk, B., and Blum, H. E. (2002). Hepatitis C: molecular virology and antiviral targets. Trends Mol. Med. 8, 476-482.

Moriya, K., Nakagawa, K., Santa, T., Shintani, Y., Fujie, H., Miyoshi, M., Tsutsumi, T., Miyazawa, T., Ishibashi, K., Horie, T., Imai, K., Todoroki, T., Kimura, S., and Koike, K. (2001). Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res., 61, 4365-4370.

Moriya, K., Yotsuyanagi, H., Shintani, Y., Fujie, H., Ishibashi, K., Matsuura, Y., Miyamura, T., Koike, K. (1997). Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J. Gen. Virol. 78: 1527-31.

Ogata, S., Florese, R. H., Nagano-Fujii, M., Hidajat, R., Deng, L., Ku, Y., Yoon, S., Saito, T., Kawata, S., and Hotta, H. (2003). Identification of hepatitis C virus (HCV) subtype 1b strains that are highly, or only weakly associated with hepatocellular carcinoma on the basis of the secondary structure of an Amino-Terminal Portion of the HCV NS3 Protein. J. Clin. Microbiol. 41, 2835-2841.

Ogunbiyi, J. O. (2001). Hepatocellular carcinoma in the developing world. Semin. Oncol. 28, 179-187.


Okabe H., Seiji, S., Kato, T., Kitahara, O., Yanagawa, R., Yamaoka, Y., Tsunoda, T., Furukawa, Y., and Nakamura, Y. (2001). Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: Identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 61, 2129-2137.

Op De Beeck, A., Cocquerel, L., and Dubuisson, J. (2000). Biogenesis of hepatitis C virus envelope glycoproteins. J. Gen. Virol. 82, 2589-2595.

Park, J. S., Yang, J. M., Min, M. K. (2000). Hepatitis C virus nonstructural protein NS4B transforms NIH3T3 cells in cooperation with the Ha-ras oncogene. Biochem. Biophys. Res. Commun. 267: 581-7.

Parkin, D. M., Pisani, P., and Ferlay, J. (1999). Estimates of the worldwide incidence of 25 major cancers in 1990. Int. J. Cancer 80, 827-841

Pflugheber, J., Fredericksen, B., Sumpter, Jr. R., Wang, C., Ware, F., Sodora, D. L., and Gale, Jr. M. (2002). Regulation of PKR and IRF-1 during hepatitis C virus RNA replication. Proc. Natl. Acad. Sci. USA 99, 4650-4655.

Pietsmann, T., Lohmann, V., Rutter, G., Kurpanek, K., and Bartenschlager, R. (2001). Characterization of cell lines carrying self-replicating hepatitis C virus RNAs. J. Virol. 75, 1252-1264.

Reddy, K. R., Wright, T. L., Pockros, P. J., Shiffman, M., Everson, G., Reindollar, R., Fried, M. W. (2001). Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C. Hepatology 33, 433-438.

Reed, K. E., Xu, J., and Rice, C. M. (1997). Phosphorylation of hepatitis C virus NS5A protein in vivo and in vitro: properties of the NS5A-associated kinase. J. Virol. 71, 7187-7197.

Rosenberg, S. (2001). Recent advances in the molecular biology of hepatitis C virus. J. Mol. Biol. 313, 451-464.



Saito, I., Miyamura, T., Ohbayashi, A., Harada, H., Katayama, T., Kikuchi, S., Watanabe, Y., Koi, S., Onji, M., Ohta, Y., Choo, Q. L., Houghton, M., and Kuo, G. (1990). Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 87, 6547-6549.

Santolini, E., Migliacio, G., and La Monica, N. (1994). Biosynthesis and biochemical properties of the hepatitis C virus core protein. J. Virol. 68, 3631-3641.

Slee, E. A., O''Connor, D. J., and Lu, X. (2004). To die or not to die: how does p53 decide? Oncogene, 23, 2809-18.

Spahn, C. M., Kieft, J. S., Grassucci, R. A., Penczek P. A., Zhou, K., Doudna, J. A., and Frank, J. (2001). Hepatitis C virus IRES RNA-induced changes in the conformation of the 40S ribosomal subunit. Science 291, 1959-1962.

Staib, F., Hussain, S. P., Hofseth, L. J., Wang, X. W., and Harris, C. C. (2003). TP53 and liver carcinogenesis. Human Mutation 21, 201-216.

Stefanovic, B., Stefanovic, L., Schnabl, B., Bataller, R., and Brenner, D. A. (2004). TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and is necessary for collagen type I synthesis. Mol. Cell. Biol. 24, 1758-1768.

Tan, S-L., and Katze, M. G. (2001). How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. Virology 284, 1-12.

Tanaka, T., Kato, N., Cho, M. J., and Shimotohno, K. (1995). A novel sequence found at the 3’ terminus of hepatitis C virus genome. Biochem Biophys. Res. Commun. 215, 744-749

Tanaka, T., Kato, N., Cho, M. J., Sugiyama, K., and Shimotohno, K. (1996). Structure of the 3’ terminus of the hepatitis C virus genome. J. Virol. 70, 3307-3312.

Tanji, Y., Kaneko, T., Satoh, S., and Shimotohno, K. (1995). Phosphorylation of hepatitis C virus-encoded nonstructural protein NS5A. J. Virol. 69, 3980-3986.

Taylor, D. R., Shi, S. T., Romano, P. R., Barber, G. N., and Lai, M. C. (1999). Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285, 107-110.

Thorgeirsson, A. and Grisham, J. W. (2002). Molecular pathogenesis of human hepatocellular carcinoma. Nature Genet. 31, 339-346.

Tsukiyama-Kohara, K., Iizuka, N., Kohara, M., and Nomoto, A. (1992). Internal ribosome enrty site within hepatitis C virus RNA. J. Virol. 66, 1476-1483.

Varaklioti, A., Vassilaki, N., Georgopoulou, U., and Mavromara, P. (2002). Alternate translation occurs within the core coding region of the hepatitis C viral genome. J. Biol. Chem. 277, 17713-17721.

Wang, C., Sarnow, P., and Siddiqui, A. (1993). Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism. J. Virol. 67, 3338-3344.

Xie, Z. C., Riezu, J. I., Lasarte, J. J., Guillen, J., Su, J. H., Civeira, M. P., and Prieto, J. (1998). Transmission of hepatitis C virus infection to tree shrews. Virology 244, 513-520.

Yamada, N., Tanihara, K., Takada, A., Yorihuzi, T., Tsutsumi, M., Shimomura, H., Tsuji, T., and Date, T. (1996). Genetic organization and diversity of the 3’ noncoding region of the hepatitis C virus genome. Virology 244, 513-520.

Yasui, K., Wakita, T., Tsukiyama, K. K., Funahashi, S. I., Ichikawa, M., Kajita, T., Moradpour, D., Wands, J. R., and Kohara, M. (1998). The native form and maturation process of hepatitis C virus core protein. J. Virol. 72, 6048-6055.

Yi, M., and Lemon, S. M. (2003). 3’ nontranslated RNA signals required for replication of hepatitis C virus RNA. J. Virol. 77, 3557-3568.

張玉泉. (2000). C型肝炎病毒核心蛋白質調控p21基因之p53非依賴性途徑. 台大醫學院生物化學暨分子生物學研究所碩士論文.
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