臺灣博碩士論文加值系統

C型肝炎病毒為一正向單股RNA病毒。雖然其基因體在不同分離株中變異性大，但5''端非轉譯區 (5'' non-coding region, 5''NCR) 及3''端非轉譯區末端含有98個核啟酸的3''X區域均有相當高的保守性，且形成特殊的二次與三次結構，被認為是病毒基因體轉譯及複製時重要的cis-elements。細胞因子及病毒本身的蛋白質藉由辨識與結合到該特殊核啟酸序列或高次結構，而調控病毒之轉譯及複製。本論文即在探討細胞因子與這兩個保守區域間的交互作用。
由gel retardation assay的結果顯示3''端非轉譯區的3''X RNA可與純化的glyceraldehyde 3-phosphate dehydrogenase (GAPDH) 產生複合物。又當以HeLa細胞萃取物與3''X RNA進行UV cross-linking實驗並以GAPDH抗體進行免疫沉澱分析時，亦可以偵測到HeLa細胞萃取物中GAPDH 與3''X RNA的交互作用。
在探討細胞因子eIF3中的170 KDa次單元體與病毒基因體5''端非轉譯區 (5''NCR RNA) 之交互作用方面，首先構築pET22b-170(781-2159)及pET22b-170(2764-3688) 兩個質體。將此質體轉型至大腸桿菌， 經大量表現並純化後分別得到eIF3-p170(223-682) 及eIF3-p170(884-1192) 融合蛋白質。經由gel retardation assay及西北方墨點分析法發現eIF3-p170(223-682) 與含有341個核啟酸序列的5''NCR RNA具有交互作用。本研究中亦將純化的eIF3-p170(223-682) 融合蛋白質免疫兔子及老鼠，得到特異性抗體。

Hepatitis C virus (HCV) is a positive, single-stranded RNA virus. Despite the overall sequence diversity of the viral genome among HCV isolates, the 5'' noncoding region (5''NCR) and the 98-nucleotide domain of the 3'' noncoding region (3''NCR), 3''X, are highly conserved. In addition, both the 5''NCR and 3''X form highly conserved stem-loop structures. It is generally believed that the conserved sequences and structures function as cis-elements that interact with cellular and viral proteins and are involved in the regulation of viral translation and replication. The specific aim of this study is to examine interactions between the conserved noncoding regions and cellular factors.
Results from gel retardation assay demonstrated formation of complexes between the HCV 3''X RNA and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). UV-crosslinking experiments with HeLa cell extract and the 3''X RNA followed by immunoprecipitation with a mouse monoclonal antibody against GAPDH also identified the interaction.
For studying interactions between the 170 KDa subunit of the eukaryotic translation initiation factor 3 (eIF3) and the HCV 5''NCR, plasmids pET22b-170(781-2159) and pET22b-170(2764-3688) were constructed and transformed into Escherichia coli BL21(DE3) and BL21(DE3)pLysS to allow the expression of eIF3-p170(223-682) and eIF3-p170(884-1192), respectively. Results from gel retardation assay and Northwestern analysis demonstrated that eIF3-p170(223-682) bound directly to the 341-nt HCV 5''NCR. Antibodies to the eIF3-p170(223-682) recombinant protein were generated.

目 錄
中文摘要…………………………………………………1
英文摘要…………………………………………………2
緒論………………………………………………………4
材料與方法………………………………………………13
結果………………………………………………………28
討論………………………………………………………39
圖表………………………………………………………48
參考文獻…………………………………………………75

Ali, N., and A. Siddiqui. 1995. Interaction of polypyrimidine tract-binding protein with the 5'' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of
translation. J. Virol. 69, 6367-6375.
Alter, M. 1995. Epidemiology of hepatitis C in the west. Semin. Liver Dis. 15, 5-14.
Asano, K., T. G. Kinzy, W. C. Merrick, and J. W. Hershey. 1997. Conservation and diversity of eukaryotic translation initiation factor eIF3. J. Biol. Chem. 272, 1101-1109.
Bartenschlager, R. 1997. Candidate targets for hepatitis C virus-specific antiviral therapy. Intervirology 40, 378-393.
Benne, R., and J. W. B. Hershey. 1978. The mechanism of action of protein synthesis initiation factors from rabbit reticulocytes. J. Biol. Chem. 253, 3078-3087.
Behrens, S. E., C. W. Grassmann, H. J. Thiel, G. Meyers, and N. Tautz. 1998. Characterization of an autonomous subgenomic pestivirus RNA replicon. J. Virol. 72, 2364-2372.
Brown, B. A., and E. Ehrenfeld. 1979. Translation of poliovirus RNA in vitro: changes in cleavage pattern and initiation sites by ribosomal salt wash. Virology 97, 396-405.
Brown-Luedi, M. L., L. J. Meyer, S. C. Milburn, P. M. P. Yau, S. Corbett, and J. W. B. Hershey. 1982. Protein synthesis initiation factors from human HeLa cells and rabbit reticulocytes are similar: comparison of protein structure, activities, and immunochemical properties. Biochemistry 21, 4202-4206.
Caselmann, W. H., and M. Alt. 1996. Hepatitis C virus infection as a major risk factor for hepatocellular carcinoma. J. Hepatology 24, 61-66.
Chen, D. S. 1995. Hepatitis C virus in chronic liver disease and hepatocellular carcinoma in Taiwan. Princess Takamatsu Symposia 25, 27-32.
Chen, P. J., M. Lin, K. F. Tai, P. C. Liu, C. J. Lin, and D. S. Chen. 1992. The Taiwanese hepatitis C virus genome: sequence determination and mapping the 5'' termini of viral genomic and antigenomic RNA. Virology 188, 102-113.
Cheng, J. C., M. F. Chang, and S. C. Chang. 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., G. Kuo, A. J. Weiner, L. R. Overby, D. W. Bradley, and M. Houghton. 1989. Isolation of a cDNA clone derived from a blood borne non-A, non-B viral hepatitis genome. Science 244, 359-362.
Choo, Q. L., K. H. Richman, J. H. Han, K. Berger, C. Lee, C. Dong, C. Gallegos, D. Coit, A. Medina-Selby, P. J. Barr, A. J. Weiner, D. W. Bradley, G. Kuo, and M. Houghton. 1991. Genetic organization and diversity of the hepatitis C virus. Proc. Natl. Acad. Sci. USA. 88, 2451-2455.
De, B. P., S. Gupta, H. Zhao, J. A. Drazba, and A. K. Banerjee. 1996. specific interatction in vitro and in vivo of glyceraldehyde-3-phosphate dehydrogenase and LA protein with cis-acting RNAs of human parainfluenza virus type 3. J. Biol. Chem. 271, 24728-24735.
Emanuele, B., S. Tisminetzky, M. Zotti, and F. E. Baralle. 1998. Functional analysis of the interaction between HCV 5''UTR and putative subunits of eukaryotic translation initiation factor eIF3. Nucleic Acids Res. 26, 3179-3187.
Failla, C., L. Tomei, and R. D. Francesco. 1994. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J. Virol. 68, 3753-3760.
Fried, M., and J. Hoofnagle. 1995. Therapy of hepatitis C virus. Semin. Liver Dis. 15, 82-91.
Hahm, B., Y. K. Kim, J. H. Kim, T. Y. Kim, and S. K. Jang. 1998. Heterogenous nuclear ribonucleoprotein L interacts with the 3'' border of the internal ribosomal entry site of hepatitis C virus. J. Virol. 72, 8782-8788.
Harris, J. I., and L. Polgar. 1965. Amino acid sequence around a reactive lysine in glyceraldehyde 3-phosphate dehydrogenase. J. Mol. Biol. 14, 630-633.
Han, J. H., and M. Houghton. 1992. Group specific sequences and conserved secondary structures at the 3'' end of HCV genome and its implication for viral replication. Nucleic Acids Res. 20, 3520.
Hellen, C. U. T., D. V. Sizova, V. G. Kolupeava, T. V. Pestova, and I. N. Shatsky. 1998. Specific Interaction of eukaryotic initation factor 3 with the 5'' nontranslated region of hepatitis C virus and classical swin fever virus RNAs. J. Virol. 72, 4775-4782.
Hershey, J. W. B., S. C. Miburn, and R. F. Duncan. 1990. Immunoblot analysis of the structure of protein synthesis initiation factor eIF3 from HeLa cells. Arch. Biochem. Biophys. 276, 6-11.
Hershey, J. W. B., K. Asano, T. Naranda, H. P. Vornlocher, P. Hanachi, and W. C. Merrick. 1996. Conservation and diversity in the structure of translation initiation factor eIF3 from humans and yeast. Biochimie 78, 903-907.
Hirikata, M., N. Kato, Y. Ootsuyama, M. Nakagawa, and K. Shimotohno. 1991. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro procession analysis. Proc. Natl. Acad. Sci. USA. 88, 5547-5551.
Honda, M., L. H. Ping, and R. C. A. Rijnbrand. 1996. Structural requirements for initiation of translation by internal ribosomal entry within genome-length hepatitis C virus. Virology 222, 31-42.
Honda, M., E. A. Brown, and S.M. Lemon. 1996. Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA. RNA 2, 955-968.
Honda, M., M. R. Beard, L. H. Ping, and S. M. Lemon. 1999. A phylogenetically conserved stem-loop structure at the 5'' border of the internal ribosome entry site of hepatitis C virus is required for cap-independent viral translation. J. Virol. 73, 1165-1174.
Honda, M., R. Rijnbrand, G. Abell, D. Kim, and S. M. Lemon. 1999. Natural variation in translational activities of the 5'' nontranslated RNAs of hepatitis C virus genotypes 1a and 1b: evidence for a long-range RNA-RNA interaction outside of the internal ribosome entry site. J. Virol. 73, 4941-4951.
Howard, C. R. 1991. Classification and taxonomy of hepatitis virus. In "Viral Hepatitis and Liver Disease" (Hollinger F. B., S. M. Lemon, H. Margolis, Ed.), pp. 890-892.
Ito, T., and M. M. C. Lai. 1997. Determination of the secondary structure of and cellular protein binding to the 3''-untranslated region of the hepatitis C virus RNA genome. J. Virol. 71, 8698-8706.
Jackson, R. J., and A. Kaminski. 1995. Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond. RNA 1, 985-1000.
Jackson, R. J., S. L. Hunt, J. E. Reynolds, and A. Kaminski. 1995. Cap-dependent and cap-independent translation: operational distinctions and mechanistic interpretations. Current Topics in Microbiology and immunology 203, 1-29.
Johnson, K. R., W. C. Merrick, W. L. Zoll, and Y. Zhu. 1997. Identification of cDNA clones for large subunit of eukaryotic translation initiation factor 3. J. Biol. Chem. 272, 7106-7113.
Kaminski, A., S. L. Hunt, J. G. Patton, and R. J. Jackson. 1995. Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA. RNA 1, 924-938.
Kao, J. H., P. J. Chen, M. Y. Lai, P. M. Yang, J. C. Sheu, T. H. Wang, and D. S. Chen. 1995. Genotypes of hepatitis C virus in Taiwan and the progression of liver disease. J. Clinical Gastroenterology 21, 233-237.
Karn, J., and M. A. Graceble. 1992. New insights into the mechanism of HIV-1 trans-activation. Trends in Genetics 8, 365-368.
Karpel, R. L., and A. C. Burchard. 1981. A basic isozyme of yeast glyceraldehyde-3-phosphate dehydrogenase with nucleic acid helix-destabilizing activity. Biochimica et Biophysica Acta 654, 256-267.
Kato, N., M. Hijikata, Y. Ootsuyama, M. Nakagawa, S. Ohkoshi, T. Sugimura, and K. Shimotohno. 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.
Kim, J. L., K. A. Morgenstern, C. Lin, T. Fox, M. D. Dwyer, J. A. Landro, S. P. Chambers, W. Markland, C. A. Lepre, E. T. O''Malley, S. L. Harbeson, C. M. Rice, M. A. Murcko, P. R. Caron, and J. A. Thomson. 1996. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87, 343-355.
Kimura Y., K. Hayashida, H. Ishibashi, Y. Niho., K. Akazawa, and Y. Yanagi. 1998. Attachment of hepatitis C virus to cultured cells: a novel predictive factor for successful interferon therapy. J. Med. Virol. 56, 25-32.
Kolykhalov, A. A., S. M. Feinstone, and C. M. Rice. 1996. Identification of a highly conserved sequence element at the 3'' terminus of hepatitis C virus genome RNA J. Virol. 70, 3363-3371.
Konarska, M. M., and P. A. Sharp. 1986. Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs. Cell 46, 845-855.
Lai, M. Y., J. H. Kao, P. M. Yang, J. T. Wang, P. J. Chen, K. W. Chan, J. S. Chu, and D. S. Chen. 1996 Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 111, 1307-1312.
Love, R. A., H. E. Parge, J. A. Wickersham, Z. Hostomsky, N. Habuka, E. W. Moomaw, T. Adachi, and Z. Hostomska. 1996. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 87, 331-342.
Lu, H. H., and E. Wimmer. 1996. Poliovirus chimeras replicating under the translational control of genetic elements of hepatitis C virus revel unusual properties of the internal ribosomal entry site of hepatitis C virus. Proc. Natl. Acad. Sci. USA. 93, 1412-1417.
Luo, G. 1999. Cellular proteins bind to the poly(U) tract of the 3''untranslated region of hepatitis C virus RNA genome. Virology 256, 105-118.
Major, M. E., and S. M. Feinstone. 1997. The molecular virology of hepatitis C. Hepatology 25, 1527-1538.
Malim, M. H., J. Hauber, S. Y. Le, J. V. Maizel, and R. Cullen. 1989. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear exort of unspliced viral mRNA. Nature 338, 254-257.
Matsuura, Y., and T. Miyamura. 1993. The molecular biology of hepatitis C virus. Semin. Virol. 4, 297-304.
Meerovitch, K., Y. V. Svitkin, H. S. Lee, F. Lejbkowicz, D. J. Kenan, E. K. Chan, V. I. Agol, J. D. Keene, and N. Sonenberg. 1993. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in the reticulocyte lysate. J. Virol. 67, 3798-3807.
Methot, N., M. S. Song, and N. Sonenberg. 1996. A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3. Mol. Cell Biol. 16, 5328-5334.
Methot, N., E. Rom, H. Olsen and N. Sonenberg. 1997. The human homologue of the yeast Prt1 protein is an integral part of the eukaryotic initiation factor 3 complex and interacts with p170. J. Biol. Chem. 272, 1110-1116.
Meyer-Siegler, K., D. J. Mauro, G. Seal, J. Wurzer, J. K. deRiel, and M. A. Sirover. 1991. A human nuclear uracil DNA glycosylase is the 37-kDa subunit of glyceraldehyde-3-phosphate dehydrogenase. Proc. Natl. Acad. Sci. USA. 88, 8460-8464.
Miller, R. H., and R. H. Porcell. 1990. Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc. Natl. Acad. Sci. USA. 87, 2057-2061.
Miyamura, T., and Y. Matsuura. 1993. Structural proteins of hepatitis C virus. Trends Microbiol. 1, 229-231.
Nagy, E., and W. F. Rigby. 1995. Glyceraldehyde-3-phosphate dehydrogenase selectively binds AU-rich RNA in the NAD(+)-binding region (Rossmann fold). J. Biol. Chem. 270, 2755-2763.
Pestova, T. V., I. N. Shatsky, S. P. Fletcher, R. J. Jackson, and C. U. T. Hellen. 1998. A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs. Genes. Dev. 12, 67-83.
Reynolds, J. E., A. Kaminski, H. J. Kettinen, A. R. Carroll, D. J. Rowlands, and R. J. Jackson. 1995. Unique features of internal initiation of hepatitis C virus RNA translation. EMBO J. 14, 6010-6020.
Rice, C. M., E. M. Lenches, S. R. Eddy, S. J. Shin, R. L. Sheers, and J. H. Strauss. 1985. Nucleotide sequence of yellow fever virus: implication for flavivirus gene expression and evolution. Science 229, 726-735.
Rice, C. M. 1996. Flaviviridae: The viruses and their replication In "Fields Virology" 3rd ed. pp. 931-959.
Richman, D. D., R. J. Whitley, and F. G. Hayden. 1997. Hepatitis C virus and hepatitis G virus. In "Clinical Virology". pp. 1193.
Rijnbrand, R., P. Bredenbeck, T. van der Straaten, L. Whetter, G. Inchauspe, S. Lemon, and W. Spaan. 1995. Almost the entire 5'' non-translated region of hepatitis C virus is required for cap-independent translation. FEBS Lett. 365, 115-119.
Saito, I., T. Miyamura, A. Ohbayashi, H. Harada, T. Katayama, S. Kikuchi, and Y. Watanabe. 1990. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA. 87, 6547-6549.
Schultz. D. E., C. C. Hardin, and S. M. Lemon. 1996. Specific interactin of glyceraldehyde 3-phosphate dehydrogenase with the 5''-nontranslated RNA of hepatitis A virus. J. Biol. Chem. 271, 14134-14142.
Simmonds, P., K. A. Rose, S. Graham, S. W. Chan, F. McOmish, B. C. Dow, E. A. Follett, P. L. Yap, and H. Marsden. 1993. Mapping of serotype-specific, immunodominant epitopes in the NS4 region of hepatitis C virus (HCV): use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3. J. Clin. Microbiol. 31, 1493-1503.
Singh, R., and M. R. Green. 1993. Sequence-specific binding of transfer RNA by glyceraldeyde-3-phosphate dehydrogenase. Science 259, 365-368.
Smith, D. B., J. Mellor, L. M. Jarvis, F. Davidson, J. Kolberg, M. Urdea, P. L. Yap, P. Simmonds, and the International HCV Collaborative Study Group. 1995. Variation of the hepatitis C virus 5'' non-coding region: implications for secondary structure, virus detection and typing. J. Gen. Virol. 76, 1749-1761.
Sorger, P. K., G. Ammerer, and D. Shore. 1989. Identification and purification of sequence-specific DNA-binding proteins. In "Protein Function: A Pratical Approach" (T. E. Creighton, Ed), pp. 199-224.
Takamizawa, A., C. Mori, I. Fuke, S. Manabe, S. Murakami, J. Fujita, E. Onishi, T. Andoh, I. Yoshida, and H. Okayama. 1991. Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol. 65, 1105-1113.
Tanaka, T., N. Kato, M. J. Cho, and K. Shimotohno. 1995. A novel sequence found at the 3'' terminus of hepatitis C virus genome. Biochem. Biophy. Res. Commun. 215, 744-749.
Tanaka, T., N. Kato, M. J. Cho, K. Sugiyama, and K. Shimotohno. 1996. Structure of the 3'' terminus of the hepatitis C virus genome. J. Virol. 70, 3307-3312.
Trachsel, H., and T. Staehelin. 1979. Initiation of mammalian protein synthesis: The multiple functions of the initiation factor eIF3. Biochim. Biophys. Acta. 565, 305-315.
Tsuchihara, K., T. Tanaka, M. Hijikata, S. Kuge, H. Toyoda, A. Nomoto, and N. Yamamoto. 1997. Specific interaction of polypyrimidine tract-binding protein with the extreme 3''-terminal structure of the hepatitis C virus genome, the 3''X. J. Virol. 71, 6720-6726.
Tsukiyama-Kohara, K., N. Iizuka, M. Kohara, and A. Nomoto. 1992. Internal ribosome entry site within hepatitis C virus RNA. J. Virol. 66, 1476-1483.
Tsukiyama-Kohara, K., K. Yamaguchi, N. Maki, Y. Ohta, K. Miki, M. Mizokami, K. Ohba, S. Tanaka, N. Hattori, and A. Nomoto. 1993. Antigenicities of group I andⅡhepatitis C virus polypeptides-molecular basis of diagnosis. Virology 192, 430-437.
Van Doorn, L. J. 1994. Review: molecular biology of the hepatitis C virus. J. Med. Virol. 43, 345-356.
Wang, C., P. Sarnow, and A. Siddiqui. 1993. Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism. J. Virol. 67, 3338-3344.
Wang, C., S. Le, N. Ali, and A. Siddiqui. 1995. An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5'' noncoding region. RNA 1, 526- 537.
Wojtowicz, N., A. Kaminski, R. Sotowski, N. Dziedzic-Goclawska and W. Stachowicz. 1995. Effect of bisphosphonates (HEBP, CL2MBP) on the process of biological mineralization in fresh bone and bone tissue de novo as a result of experimental osteogenesis induction in guinea pigs. Polski Tygodnik Lekarski. 50, 45-47.
Yamada, N., K. Tanihara, A. Takada. T. Yorihuzi, M. Tsutsumi, H. Shimomura, T. Tsuji, and T. Date. 1996. Genetic organization and diversity of the 3'' noncoding region of the hepatitis C genome. Virology 223, 255-261.
Yamashita, T., S. Kaneko, Y. Shirota, W. Qin, T. Nomura, K. Kobayashi, and S. Murakami. 1998. RNA-dependent RNA polymerase activity of the soluble recombinant hepatitis C virus NS5B protein truncated at the C-terminal region. J. Biol. Chem. 273, 15479-15486.
Yanagi M., M. S. Claire, M. Shapiro, S. U. Emerson, R. H. Purcell, and J. Bukh. 1998. Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo. Virology 244, 161-172.
Yanagi, M., R. H. Purcell, S. U. Emerson, and J. Bukh. 1997. Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. Proc. Natl. Acad. Sci. USA. 94, 8738-8743.
Yen, J. H., S. C. Chang, C. R. Hu, S. C. Chu, S. S. Lin, Y. S. Hsieh, and M. F. Chang. 1995. Cellular proteins specifically bind to the 5''- noncoding region of hepatitis C virus RNA. Virology 208, 723-732.
Yusuke, I., M. Miyazaki, R. Ohashi, T. Tsuji, K. Fukaya, H. Kouchi, T. Uemura, K. Mihara, and M. Namba. 1998. Ubiquitous presence of cellular protein that specifically bind to the 3'' terminal region of hepatitis C virus. Biochem. Biophy. Res. Commun. 245, 198-203.
Zang, W. Q., A. M. Fieno, R. A. Grant, and T. S. Yen. 1998. Identification of glyceraldehyde-3-phosphate dehydrogenase as a cellular protein that binds to the hepatitis B virus posttranscriptional regulatory element. Virology 248, 46-52.
Zeng, L., B. Falgout, and L. Markoff. 1998. Identification of specific nucleotide sequences within the conserved 3''-SL in the Dengue type 2 virus genome required for replication. J. Virol. 72, 7510-7522.
胡傳仁. 1995. C型肝炎病毒5''端非轉譯區與細胞因子交亙作用之探討. 碩士論文.
葉名宜. 1997. C型肝炎病毒5''端非轉譯區結構與核啟酸序列對病毒轉譯的影響. 碩士論文.