Properties of the hepatitis C virus core protein: A structural protein that modulates cellular processes

Journal of Viral Hepatitis

Volumn 7, Issue 1, 2000, Pages 2-14

  McLauchlan, John ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

Core protein; Core protein and cellular pathways; HCV core protein; HCV virus assembly; Maturation of core protein

Indexed keywords

CORE PROTEIN; FAS ANTIGEN; LYMPHOTOXIN; RIBONUCLEOPROTEIN; TRANSCRIPTION FACTOR; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR; VIRUS RNA;

AMINO ACID SEQUENCE; APOPTOSIS; HEPATITIS C VIRUS; HOST CELL; HUMAN; LIPID METABOLISM; NONHUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN RNA BINDING; REVIEW; VIRUS ASSEMBLY; VIRUS CORE;

ANIMALS; HEPACIVIRUS; HEPATITIS C; HUMANS; RATS; VIRAL CORE PROTEINS; VIRUS ASSEMBLY;

EID: 0034053296     PISSN: 13520504     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2893.2000.00201.x     Document Type: Review

References (120)

1. 1 Kuo G, Choo Q-L, Alter HJ et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 1989; 244: 362-364.
2. 2 Di Bisceglie AM. Hepatitis C. Lancet 1998; 351: 351-355.
3. 3 Lefkowitch JH, Schiff ER, Davis GL et al. and the Hepatitis Interventional Therapy Group. Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. Gastroenterology 1993; 104: 595-603.
4. 4 Scheuer PJ, Ashrafzadeh P, Sherlock S, Brown D, Dusheiko GM. The pathology of hepatitis C. Hepatology 1992; 15: 567-571.
5. 5 Baiocchi L, Tisone G, Palmieri G et al. Hepatic steatosis: a specific sign of hepatitis C reinfection after liver transplantation. Liver Transplant Surg 1998; 4: 441-447.
6. 6 Gish RG. Standards of treatment in chronic hepatitis C. Semin Liver Dis 1999; 19: 35-47.
7. 7 McHutchinson JG, Poynard T. Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C. Semin Liver Dis 1999; 19: 57-65.
8. 8 Kato N, Hijikita M, Ootsuyama Y et al. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci USA 1990; 87: 9524-9528.
9. 9 Tanaka T, Lau JYN, Mizokami M et al. Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia. J Hepatol 1995; 23: 742-745.
10. 10 Yasui K, Wakita T, Tsukiyama-Kohara K et al. The native form and maturation process of hepatitis C virus core protein. J Virol 1998; 72: 6048-6055.
11. 11 Bartenschlager R. The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy. J Viral Hepat 1999; 6: 165-182.
12. 12 Clarke B. Molecular virology of hepatitis C virus. J Gen Virol 1997; 78: 2397-2410.
13. 13 Robertson B, Myers G, Howard C et al. Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. Arch Virol 1998; 143: 2493-2503.
14. 14 Hijikita M, Kato N, Ootsuyuma Y, Nakagawa M, Shimotohno K. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci USA 1991; 88: 5547-5551.
15. 15 Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM. Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol 1993; 67: 1385-1395.
16. 16 Selby MJ, Choo Q-L, Berger K et al. Expression, identification and subcellular localization of the proteins encoded by the hepatitis C viral genome. J Gen Virol 1993; 74: 1103-1113.
17. 17 Hussy P, Langen H, Mous J, Jacobsen H. Hepatitis C virus core protein: carboxy-terminal boundaries of two processed species suggest cleavage by a signal peptide peptidase. Virology 1996; 224: 93-104.
18. 18 Lo S-Y, Selby M, Tong M, Ou J-H. Comparative studies of the core gene products of two different hepatitis C virus isolates: two alternative forms determined by a single amino acid substitution. Virology 1994; 199: 124-131.
19. 19 Lo S-Y, Masiarz F, Hwang SB, Lai MMC, Ou J-H. Differential subcellular localization of hepatitis C virus core gene products. Virology 1995; 213: 455-461.
20. 20 Santolini E, Migliaccio G, La Monica N. Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol 1994; 68: 3631-3641.
21. 21 Suzuki R, Matsuura Y, Suzuki T et al. Nuclear localization of the truncated hepatitis C virus core protein with its hydrophobic C-terminus deleted. J Gen Virol 1995; 76: 53-61.
22. 22 Moradpour D, Englert C, Wakita T, Wands JR. Characterization of cell lines allowing tightly regulated expression of hepatitis C virus core protein. Virology 1996; 222: 51-63.
23. 23 Liu Q, Tackney C, Bhat RA, Prince AM, Zhang P. Regulated processing of hepatitis C virus core protein is linked to subcellular localization. J Virol 1997; 71: 657-662.
24. 24 Takeuchi K, Kubo Y, Boonmar S et al. The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequence of two isolates derived from an experimentally infected chimpanzee and healthy human carriers. J Gen Virol 1990; 71: 3027-3033.
25. 25 Fuchs K, Motz M, Schreier E, Zachoval R, Deinhardt F, Roggcndorf M. Characterization of nucleotide sequences from European hepatitis C virus isolates. Gene 1991; 103: 163-169.
26. 26 Takamizawa A, Mori C, Fuke I et al. Structure and organisation of the hepatitis C virus genome isolated from human carriers. J Virol 1991; 65: 1105-1113.
27. 27 Okamoto H, Kurai K, Okada S-I et al. Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology 1992; 188: 331-341.
28. 28 Bukh J, Purcell RH, Miller RH. Sequence analysis of the core gene of 14 hepatitis C virus genotypes. Proc Natl Acad Sci USA 1994; 91: 8239-8243.
29. 29 Von Heijne G. The signal peptide. J Membr Biol 1990; 115: 195-201.
30. 30 Martoglio B, Dobberstein B. Signal sequences: more than just greasy peptides. Trends Cell Biol 1998; 8: 410-415.
31. 31 Gonzalez-Peralta RP, Fang JWS, Davis CL et al. Optimization for the detection of hepatitis C virus antigens in the liver. J Hepatol 1994; 20: 143-147.
32. 32 Yap SH, Willems M, Van den Oord J et al. Detection of hepatitis C virus antigen by immunohistochemical staining: a histological marker of hepatitis C virus infection. J Hepatol 1994; 20: 275-281.
33. 33 Nouri-Aria KT, Sallie R, Mizokami M, Portmann BC, Williams R. Intrahepatic expression of hepatitis C virus antigens in chronic liver disease. J Pathol 1995; 175: 77-83.
34. 34 Lau JYN, Krawczynski K, Negro F, Gonzalez-Peralta RP. In situ detection of hepatitis C virus - a critical appraisal. J Hepatol 1996; 24: 43-51.
35. 35 Harada S, Watanabe Y, Takeuchi K et al. Expression of processed core protein of hepatitis C virus in mammalian cells. J Virol 1991; 65: 3015-3021.
36. 36 Barba G, Harper F, Harada T et al. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci USA 1997; 94: 1200-1205.
37. 37 Murphy DJ, Vance J. Mechanisms of lipid-body formation. Trends Biol Sci 1999; 24: 109-115.
38. 38 Londos C, Brasaemle DL, Schultz CJ, Segrcst JP, Kimmel AR. Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Cell Dev Biol 1999; 10: 51-58.
39. 39 Warden CH, Hedrick CC, Qiao J-H, Castellani LW, Lusis AJ. Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science 1993; 261: 469-472.
40. 40 Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C. Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res 1997; 38: 2249-2263.
41. 41 Heid HW, Moll R, Schwetlick I, Rackwitz H-R, Keenan TW. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res 1998; 294: 309-321.
42. 42 Marusawa H, Hijikita M, Chiba T, Shimotohno K. Hepatitis C virus core protein inhibits Fas-and tumor necrosis factor alpha-mediated apoptosis via NF-κB activation. J Virol 1999; 73: 4713-4720.
43. 43 Shimuzu YK, Feinstone SM, Kohara M, Purcell RH, Yoshikura H. Hepatitis C virus: detection of intracellular virus particles by electron microscopy. Hepatology 1996; 23: 205-209.
44. 44 Takahashi K, Kishimoto S, Yoshizawa H, Okamoto H, Yoshikawa A, Mishiro S. p26 protein and 33-nm particle associated with nucleocapsid of hepatitis C virus recovered from the circulation of infected hosts. Virology 1992; 191: 431-434.
45. 45 Baumert TF, Ito S, Wong DT, Liang TJ. Hepatitis C virus structural proteins assemble into viruslike particles in insect cells. J Virol 1998; 72: 3827-3836.
46. 46 Wang YH, Trowbridge R, Gowans EJ. Expression and interaction of the hepatitis C virus structural proteins and the 5′ untranslated region in baculovirus infected cells. Arch Virol 1997; 142: 2211-2223.
47. 47 Lu HH, Wimmer E. Poliovirus chimeras replicating under the translational control of genetic elements of hepatitis C virus reveal unusual properties of the internal ribosomal entry site of hepatitis C virus. Proc Natl Acad Sci USA 1996; 93: 1412-1417.
48. 48 Zhao WD, Wimmer E, Lahser FC. Poliovirus/hepatitis C virus (internal ribosome entry site-core) chimeric viruses: improved growth properties through modification of a proteolytic cleavage site and requirement for core RNA sequences but not for core-related peptides. J Virol 1999; 73: 1546-1554.
49. 49 Matsumoto M, Hwang SB, Jeng K-S, Zhu N, Lai MMC. Homotypic interaction and multimerization of hepatitis C virus core protein. Virology 1996; 218: 43-51.
50. 50 Nolandt O, Kern V, Muller H et al. Analysis of hepatitis C virus core protein interaction domains. J Gen Virol 1997; 78: 1331-1340.
51. 51 Yan BS, Tam MH, Syu WJ. Self-association of the C-terminal domain of the hepatitis-C virus core protein. Eur J Biochem 1998; 258: 100-106.
52. 52 Ralston R, Thudium K, Berger K et al. Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses. J Virol 1993; 67: 6753-6761.
53. 53 Lo SY, Selby MJ, Ou J-H. Interaction between hepatitis C virus core protein and E1 envelope protein. J Virol 1996; 70: 5177-5182.
54. 54 Bomsztyk K, Van Seuningen I, Suzuki H, Denisenko O, Ostrowski J. Diverse molecular interactions of the hnRNP K protein. FEBS Lett 1997; 403: 113-115.
55. 55 Hobert O, Jallal B, Schlessinger J, Ullrich A. Novel signaling pathway suggested by SH3 domain-mediated p95 (vav)/ heterogeneous ribonucleoprotein K interaction. J Biol Chem 1994; 269: 20225-20228.
56. 56 Bustelo XR, Suen K-L, Michael WM, Dreyfuss G, Barbacid M. Association of the vav proto-oncogene product with poly (rC)-specific RNA-binding proteins. Mol Cell Biol 1995; 15: 1324-1332.
57. 57 Van Seuningen I, Ostrowski J, Bustelo XR, Sleath PR, Bomsztyk K. The K protein domain that recruits the interleukin 1-responsive K protein kinase lies adjacent to a cluster of c-Src and Vav SH3-binding sites. Implications that K protein acts as a docking platform. J Biol Chem 1995; 270: 26976-26985.
58. 58 Hsieh T-Y, Matsumoto M, Chou H-C et al. Hepatitis C virus core protein interacts with heterogeneous nuclear ribonucleoprotein K. J Biol Chem 1998; 273: 17651-17659.
59. 59 Chen C-M, You L-R, Hwang L-H, Lee Y-HW. Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-β receptor modulates the signal pathway of the lymphotoxin-β receptor. J Virol 1997; 71: 9417-9426.
60. 60 Matsumoto M, Hsieh T-Y, Zhu N et al. Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-β receptor. J Virol 1997; 71: 1301-1309.
61. 61 Ware CF, Van Arsdale TL, Crowe PD, Browning JL. The ligands and receptors of the lymphotoxin system. Curr Top Microbiol Immunol 1995; 198: 175-218.
62. 62 Force WR, Walter BN, Hession C et al. Mouse lymphotoxin-beta receptor: molecular genetics, ligand binding, and expression. J Immunol 1995; 155: 5280-5288.
63. 63 Koni PA, Sacca R, Lawton P, Browning JL, Ruddle NH, Flavell RA. Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 1997; 6: 491-500.
64. 64 Zhu N, Khoshnan A, Schneider R et al. Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 1998; 72: 3691-3697.
65. 65 Tartaglia LA, Goeddel DV. Two TNF receptors. Immunol Today 1992; 13: 151-153.
66. 66 Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 1994; 6: 959-962.
67. 67 Ashkenazi A, Dixit VM. Death receptors: signalling and modulation. Science 1998; 281: 1305-1308.
68. 68 Mamiya N, Worman HJ. Hepatitis C virus core protein binds to a DEAD box RNA helicase. J Biol Chem 1999; 274: 15751-15756.
69. 69 Owsianka AM, Patel AH. Hepatitis C virus core protein interacts with a human DEAD box protein DDX3. Virology 1999; 257: 330-340.
70. 70 You L-R, Chen C-M, Yeh T-S et al. Hepatitis C virus core protein interacts with a cellular putative RNA helicase. J Virol 1999; 73: 2841-2853.
71. 71 Wassarman DA, Steitz JA. Alive with DEAD proteins. Nature 1991; 349: 463-464.
72. 72 Schmid SR, Linder P. D-E-A-D protein family of putative RNA helicase. Mol Microbiol 1992; 6: 283-291.
73. 73 Fuller-Pace FV. RNA helicases: modulators of RNA structure. Trends Cell Biol 1994; 4: 271-274.
74. 74 Rudin CM, Thompson CB. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med 1997; 48: 267-281.
75. 75 Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP. Tumor necrosis factor and Fas signalling mechanisms. Annu Rev Immunol 1999; 17: 331-367.
76. 76 Rathmell JC, Thompson CB. The central effectors of cell death in the immune system. Annu Rev Immunol 1999; 17: 781-828.
77. 77 Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998; 281: 1312-1316.
78. 78 Sethi JK, Hotamisligil GS. The role of TNFα in adipocyte metabolism. Cell Dev Biol 1999; 10: 19-29.
79. 79 Memon RA, Feingold KR, Moser AH, Fuller J, Grunfeld C. Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines. Am J Physiol (Endocrinol Metab) 1998; 274: E210-217.
80. 80 Ruggieri A, Harada T, Matsuura Y, Miyamura T. Sensitization to Fas-mediated apoptosis by hepatitis C virus core protein. Virology 1997; 229: 68-76.
81. 81 Hasegawa J, Kamada S, Kamiike W et al. Involvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis. Cancer Res 1996; 56: 1713-1718.
82. 82 Suzuki A, Tsutomi Y, Akahane K, Araki T, Miura M. Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP. Oncogene 1998; 17: 931-940.
83. 83 Suzuki A, Tsutomi Y, Yamamoto N, Shibutani T, Akahane K. Mitochondrial regulation of cell death: mitochondria are essential for procaspase 3-p21 complex formation to resist Fas-mediated cell death. Mol Cell Biol 1999; 19: 3842-3847.
84. 84 Scaffidi C, Fulda S, Srinivasan A et al. Two CD95 (Apo-1/ Fas) signalling pathways. EMBO J 1998; 17: 1675-1687.
85. 85 Ray RB, Meyer K, Steele R, Shrivastava A, Aggarwal BB, Ray R. Inhibition of tumor necrosis factor (TNF-α)-mediated apoptosis by hepatitis C virus core protein. J Biol Chem 1998; 273: 2256-2259.
86. 86 Beidler DR, Tewari M, Friesen PD, Poirier G, Dixit VM. The baculovirus p35 protein inhibits Fas-and tumor necrosis factor-induced apoptosis. J Biol Chem 1995; 270: 16526-16528.
87. 87 Li F, Srinivasan A, Wang Y, Armstrong RC, Tomaselli KJ, Fritz LC. Cell-specific induction of apoptosis by microinjection of cytochrome c. BcI-xL has activity independent of cytochrome c release. J Biol Chem 1997; 272: 30299-30305.
88. 88 Jänicke RU, Sprengart ML, Wati MR, Porter AG. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998; 273: 9357-9360.
89. 89 Oberhammer F, Wilson JW, Dive C et al. Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO J 1993; 12: 3679-3684.
90. 90 Ray RB, Lagging LM, Meyer K, Ray R. Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol 1996; 70: 4438-4443.
91. 91 Chang J, Yang S-H, Cho Y-G, Hwang SB, Hahn YS, Sung YC. Hepatitis C virus core protein 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 1998; 72: 3060-3065.
92. 92 Tsuchihara K, Hijikita M, Fukuda K, Kuroki T, Yamamoto N, Shimotohno K. Hepatitis C virus core protein regulates cell growth and signal transduction pathway transmitting growth stimuli. Virology 1999; 258: 100-107.
93. 93 Shih C-M, Lo SJ, Miyamura T, Chen S-Y, Lee Y-HW. Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol 1993; 67: 5823-5832.
94. 94 Fong TL, DiBisceglie AM, Waggoner JG, Banks SM, Hoofnagle JH. The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. Hepatology 1991; 14: 64-67.
95. 95 Liaw Y-F, Lin SM, Sheen I-S, Chu CM. Acute hepatitis C virus superinfection followed by spontaneous HBeAg sero-conversion and HBsAg elimination. Infection 1991; 250: 54-55.
96. 96 Sheen I-S, Liaw Y-F, Chu C-M, Pao C-C. Role of hepatitis C virus infection in spontaneous hepatitis B surface antigen clearance during chronic hepatitis B virus infection. J Infect Dis 1992; 165: 831-834.
97. 97 Shih C-M, Chen C-M, Chen S-Y, Lee Y-HW. Modulation of the trans-suppression activity of hepatitis C virus core protein by phosphorylation. J Virol 1995; 69: 1160-1171.
98. 98 Ray RB, Lagging LM, Meyer K, Steele R, Ray R. Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein. Virus Res 1995; 37: 209-220.
99. 99 Ray RB, Steele R, Meyer K, Ray R. Transcriptional repression of p53 promoter by hepatitis C virus core protein. J Biol Chem 1997; 272: 10983-10986.
100. WAF1/Cip1/Sid1 promoter activity. Gene 1998; 208: 331-336.
101. 101 You L-R, Chen C-M, Lee Y-HW. Hepatitis C virus core protein enhances NF-κB signal pathway triggering by lymphotoxin-β receptor ligand and tumor necrosis factor alpha. J Virol 1999; 73: 1672-1681.
102. 102 Shrivastava A, Manna SK, Ray R, Aggarwal BB. Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors. J Virol 1998; 72: 9722-9728.
103. 103 Baldwin JA. The NF-κB and IκB proteins: new discoveries and insights. Annu Rev Imnumol 1996; 14: 649-681.
104. 104 Baeuerle PA, Baltimore D. NF-κB: 10 years after. Cell 1996; 87: 13-20.
105. 105 Verma IM, Stevenson J. IκB kinase: beginning not the end. Proc Natl Acad Sci USA 1997; 94: 11758-11760.
106. 106 Lin BH, Williamskipp C, Tao YX et al. NF-kappa B functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type. Cell Death Differ 1999; 6: 570-582.
107. 107 Peters VB, Sperber KE. The effect of viruses on the ability to present antigens via the major histocompatibility complex. Microbes Infect 1999; 1: 335-345.
108. 108 Klagge IM, Schneider-Schaulies S. Virus interactions with dendritic cells. J Gen Virol 1999; 80: 823-833.
109. 109 Kanto T, Hayashi N, Takehara T et al. Impaired allostimulatory capacity of peripheral blood cells recovered from hepatitis C virus-infected individuals. J Immunol 1999; 162: 5584-5591.
110. 110 Hiasa Y, Horiike N, Akbar SMF et al. Low stimulatory capacity of lymphoid dendritic cells expressing hepatitis C virus genes. Biochem Biophys Res Commun 1998; 249: 90-95.
111. 111 Large MK, Kittlesen DJ, Hahn YS. Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatitis C virus persistence. J Immunol 1999; 162: 931-938.
112. 112 Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Host-and disease-specific factors affecting steatosis in chronic hepatitis. J Hepatol 1998; 29: 198-206.
113. 113 Hourigan LF, MacDonald GA, Purdie D et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 1999; 29: 1215-1219.
114. 114 Moriya K, Yotsuyanagi H, Shintani Y et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 1997; 78: 1527-1531.
115. 115 Moriya K, Fujie H, Shintani Y et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nature Med 1998; 4: 1065-1067.
116. 116 Kawamura T, Furusaka A, Koziel MJ et al. Transgenic expression of hepatitis C virus structural proteins in the mouse. Hepatology 1997; 25: 1014-1021.
117. 117 Pasquinelli C, Shoenberger JM, Chung J et al. Hepatitis C virus core and E2 protein expression in transgenic mice. Hepatology 1997; 25: 719-727.
118. 118 Wakita T, Taya C, Katsume A et al. Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system. J Biol Chem 1998; 273: 9001-9006.
119. 119 Reisner Y, Dagan S. The trimera mouse: generating human monoclonal antibodies and an animal model for human diseases. Trends Biotechnol 1998; 16: 242-246.
120. 120 Nomura T. Practical development of genetically engineered animals as human disease models. Lab Anim Sci 1997; 47: 113-117.