1887

Chapter 10 : Hepatitis C Virus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Hepatitis C Virus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818289/9781555811303_Chap10-1.gif /docserver/preview/fulltext/10.1128/9781555818289/9781555811303_Chap10-2.gif

Abstract:

Using molecular biological techniques, a viral genome was cloned from the serum of a chimpanzee infected with non-A, non-B (NANB) hepatitis. The virus was designated the hepatitis C virus (HCV) and has been shown to be the major causative agent of NANB hepatitis. Since then, HCV has emerged as a major cause of chronic liver disease with a prevalence of 1.8% in the United States. Studies of HCV have been hampered by the lack of an easy animal or tissue culture model. HCV has been classified as the third genus of the family, which, together with pestiviruses and flaviviruses, are single-stranded RNA viruses with a positive polarity and share a similar genomic structure and organization. Immunohistochemical studies have shown that HCV antigens are widespread in the liver within the cytoplasm of hepatocytes and also within the infiltrating lymphoid aggregates. HCV appears to be the dominant factor associated with hepatocellular carcinoma (HCC) in areas with intermediate rates of HCC, whereas hepatitis B virus is the dominant factor in areas with higher rates of HCC. Great strides have been made in understanding the virology and immunology of the human immunodeficiency virus (HIV), and therapeutic regimens have recently achieved suppression of viral replication to undetectable levels. Therapeutic trials for NANB hepatitis using interferon-alpha were initiated in the 1980s before diagnostic tests for HCV were available. The development of infectious cDNA clones is a great stride forward as it will permit the use of a standard infectious inoculum without quasispecies.

Citation: Wong D, Walker B. 1998. Hepatitis C Virus, p 301-329. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch10

Key Concept Ranking

Humoral Immune Response
0.52922297
Hepatitis C virus
0.5075182
Hepatitis B virus
0.48948354
0.52922297
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Structure and function of the various HCV genomic regions and proteins. See Table 1 .

Citation: Wong D, Walker B. 1998. Hepatitis C Virus, p 301-329. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch10
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818289.chap10
1. Aach, R. D.,, C. E. Stevens,, F. B. Hollinger,, J. W. Mosley,, D. A. Peterson,, P. E. Taylor,, R. G. Johnson,, L. H. Barbosa,, and G. J. Nemo. 1991. Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays. N. Engl. J. Med. 325: 1325 1329.
2. Adams, N. J.,, R. W. Chamberlain,, L. A. Taylor,, F. Davidson, C. K. Lin, R. M. Elliott, and P. Simmonds. 1997. Complete coding sequence of hepatitis C virus genotype 6a. Biochem. Biophys. Res. Commun. 234: 393 396.
3. Alter, H. J.,, P. V. Holland,, A. G. Morrow,, R. H. Purcell,, S. M. Feinstone,, and Y. Moritsugu. 1975. Clinical and serological analysis of transfusion-associated hepatitis. Lancet 2: 838 841.
4. Alter, H. J.,, R. H. Purcell,, P. V. Holland,, and H. Popper. 1978. Transmissible agent in non-A, non-B hepatitis. Lancet 1: 459 463.
5. Alter, M. J. 1997. Epidemiology of hepatitis C. Hepatology 26: 62S 65S.
6.Anonymous. 1997. National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C. Hepatology 26: 2S10S.
7. Asabe, S. L, Y. Tanji, S. Satoh, T. Kaneko, K. Kimura, and K. Shimotohno. 1997. The N-terminal region of hepatitis C virus-encoded NS5A is important for NS4A-dependent phosphorylation. J. Virol. 71: 790 796.
8. Bachmann, M. F.,, T. M. Kundig,, H. Hengartner,, and R. M. Zinkernagel. 1997. Protection against immunopathological consequences of a viral infection by activated but not resting cytotoxic T cells: T cell memory without "memory T cells"? Proc. Natl. Acad. Sci. USA 94: 640 645.
9. Ballardini, G.,, P. Groff,, F. Giostra,, R. Francesconi,, D. Zauli,, B. Gianpaolo,, M. Lenzi,, F. Cassani,, and F. Bianchi. 1994. Hepatocellular expression of HLA-A, B, C molecules predicts primary response to interferon in patients with chronic hepatitis C. Am. J. Clin. Pathol. 102: 746 751.
10. Ballardini, G.,, P. Groff,, P. Pontisso,, F. Giostra,, R. Francesconi,, M. Lenzi,, D. Zauli,, A. Alberti,, and F. B. Bianchi. 1995. Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C. J. Clin. Invest. 95: 2067 2075.
11. Barba, G.,, F. Harper,, T. Harada,, M. Kohara,, S. Goulinet,, Y. Matsuura,, G. Eder,, Z. Schaff,, M. J. Chapman,, T. Miyamura,, and C. Brechot. 1997. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc. Natl. Acad. Sci. USA 94: 1200 1205.
12. Bartenschlager, R.,, L. Ahlborn-Laake,, J. Mous,, and H. Jacobsen. 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 3844.
13. Bartenschlager, R.,, V. Lohmann,, T. Wilkinson,, and J. O. Koch. 1995. Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation. J. Virol. 69: 7519 7528.
14. Battegay, M.,, J. Fikes,, A. M. Di Bisceglie,, P. A. Wentworth,, A. Sette,, E. Celis,, W.-M. Ching,, A. Grakoui, C. M. Rice, K. Kurokohchi, J. A. Berzofsky, J. H. Hoofnagle, S. M. Feinstone, and T. Akatsuka. 1995. Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. J. Virol. 69: 2462 2470.
15. Behrens, S.-E.,, L. Tornei,, and R. De Francesco. 1996. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J. 15: 12 22.
16.Bellobuono, A., L. Mondazzi, S. Tempini, E. Silini, F. Vicari, and G. Ideo. 1997. Ribavirin and interferon-alpha combination therapy vs interferon-alpha alone in the retreatment of chronic hepatitis C: a randomized clinical trial. J. Viral Hepatitis 4: 185191.
17. Benvegnu, L.,, P. Pontisso,, D. Cavalletto,, F. Noventa,, L. Chemello,, and A. Alberti. 1997. Lack of correlation between hepatitis C virus genotypes and clinical course of hepatitis C virus-related cirrhosis. Hepatology 25: 211 215.
18. Berman, M.,, H. J. Alter,, K. G. Ishak,, R. H. Purcell,, and E. A. Jones. 1979. The chronic sequelae of non-A, non-B hepatitis. Ann. Intern. Med. 91: 1 6.
19. Bianchi, L.,, V. J. Desmet,, H. Popper,, P. J. Scheuer,, L. M. Aledort,, and P. D. Berk. 1987. Histologic patterns of liver disease in hemophiliacs, with special reference to morphologic characteristics of non-A, non-B hepatitis. Semin. Liver Dis. 7: 203 209.
20. Blight, K.,, R. R. Lesniewski,, J. T. LaBrooy,, and E. J. Gowans. 1994. Detection and distribution of hepatitis C-specific antigens in naturally infected liver. Hepatology 20: 553 557.
21. Blight, K. J.,, and C. M. Rice. 1997. Secondary structure determination of the conserved 98-base sequence at the 3' terminus of hepatitis C virus genome RNA. J. Virol. 71: 7345 7352.
22. Bradley, D. W.,, J. E. Maynard,, H. Popper,, E. H. Cook,, J. W. Ebert,, K. A. McCaust-land,, C. A. Schable,, and H. A. Fields. 1983. Posttransfusion non-A, non-B hepatitis: physicochemical properties of two distinct agents, J. Infect. Dis. 148: 254 265.
23. Bradley, D. W.,, K. A. McCaustland,, E. H. Cook,, C. A. Schable,, J. W. Ebert,, and J. E. Maynard. 1985. Posttransfusion non-A, non-B hepatitis in chimpanzees. Physico-chemical evidence that the tubule-forming agent is a small, enveloped virus. Gastroenterology 88: 773 779.
24. Brechot, C.,, and D. Kremsdorf. 1993. Genetic variation of the hepatitis C virus (HCV) genome: random events or a clinically relevant issue? J. Hepatol. 17: 265 268.
25. Brown, E. A.,, H. Zhang,, L. H. Ping,, and S. M. Lemon. 1992. Secondary structure of the 5' nontranslated regions of hepatitis C virus and pestivirus genomic RNAs. Nucleic Acids Res. 20: 5041 5045.
26. Bruix, J.,, J. M. Barrera,, X. Calvet,, G. Ercilla,, J. Costa,, J. M. Sanchez-Tapias,, M. Ventura,, M. Vail,, M. Bruguera,, and C. Bru. 1989. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis [see comments] Lancet ii: 1004 1006.
27. Bukh, J.,, R. H. Miller,, M. C. Kew,, and R. H. Purcell. 1993. Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 90: 1848 1851.
28. Bukh, J.,, R. H. Purcell,, and R. H. Miller. 1992. Sequence analysis of the 5' noncoding region of hepatitis C virus. Proc. Natl. Acad. Sci. USA 89: 4942 4946.
29. Bukh, J.,, R. H. Purcell,, and R. H. Miller. 1993. At least 12 genotypes of hepatitis C. virus predicted by sequence analysis of the putative El gene of isolates collected worldwide. Proc. Natl. Acad. Sci. USA 90: 8234 8238.
30. Bukh, J.,, R. H. Purcell,, and R. H. Miller. 1994. Sequence analysis of the core gene of 14 hepatitis C virus genotypes. Proc. Natl. Acad. Sci. USA 91: 8239 8243.
31. Carithers, R. L., Jr., and S. S. Emerson. 1997. Therapy of hepatitis C: meta-analysis of interferon alfa-2b trials. Hepatology 26: 83S 88S.
32. Cerny, A.,, J. G. McHutchison,, C. Pasquinelli,, M. E. Brown,, M. A. Brothers,, B. Grabscheid,, P. Fowler,, M. Houghton,, and F. V. Chisari. 1995. Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. J. Clin. Invest. 95: 521 530.
33. Chamberlain, R. W.,, N. Adams,, A. A. Saeed,, P. Simmonds,, and R. M. Elliott. 1997. Complete nucleotide sequence of a type 4 hepatitis C virus variant, the predominant genotype in the Middle East. J. Gen. Virol. 78: 1341 1347.
34. Chambers, T. J.,, R. C. Weir,, A. Grakoui,, D. W. McCourt,, J. F. Bazan,, R. J. Fletterick,, and C. M. Rice. 1990. Evidence that the N-terminal domain of nonstructural protein NS3 from yellow fever virus is a serine protease responsible for site-specific cleavages in the viral polyprotein. Proc. Natl. Acad. Sci. USA 87: 8898 8902.
35. Chan, S.-W.,, F. McOmish,, E. C. Holmes,, B. Dow,, J. F. Peutherer,, E. Follett,, P. L. Yap,, and P. Simmonds. 1992. Analysis of a new hepatitis C virus type and its phylogenetic relationship to existing variants. J. Gen. Virol. 73: 1131 1141.
36. Chayama, K.,, A. Tsubota,, M. Kobayashi,, K. Okamoto,, M. Hashimoto,, Y. Miyano,, H. Koike,, I. Koida,, Y. Arase,, S. Saitoh,, Y. Suzuki,, N. Murashima,, K. Ikeda,, and H. Kumada. 1997. Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype lb hepatitis C virus infection [see comments] Hepatology 25: 745 749.
37. Chayama, K.,, A. Tsubota,, I. Koida,, Y. Arase,, S. Saitoh,, K. Ikeda,, and H. Kumada. 1994. Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C. J. Gen. Virol. 75: 3623 3628.
38. Chemello, L.,, L. Cavalletto,, F. Noventa,, P. Bonetti,, C. Casarin,, E. Bernardinello,, P. Pontisso,, C. Donada,, P. Casarin,, and F. Belussi. 1995. Predictors of sustained response, relapse and no response in patients with chronic hepatitis C treated with interferon-alpha. J. Viral Hepatitis 2: 91 96.
39. Chen, P. J.,, M. H. 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 viral genomic and antigenomic RNA. Virology 188: 102 113.
40. Chisari, F. V. 1997. Cytotoxic T cells and viral hepatitis, J. Clin. Invest. 99: 1472 1477.
41. 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 C genome. Science 244: 359 362.
42. 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.
43. Choo, S. H.,, H. S. So,, J. M. Cho,, and W. S. Ryu. 1995. Association of hepatitis C virus particles with immunoglobulin: a mechanism for persistent infection. J. Gen. Virol. 76: 2337 2341.
44. Chun, T.-W.,, L. Stuyver,, S. B. Mizell,, L. A. Ehler,, J. M. Mican,, M. Baseler,, A. L. Lloyd,, M. A. Nowak,, and A. S. Fauci. 1997. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl. Acad. Sci. USA 94: 13193 13197.
45. Colombo, M.,, R. de Franchis,, E. Del Ninno,, A. Sangiovanni,, C. De Fazio,, M. Tom-masini,, M. F. Donato,, A. Piva,, V. Di Carlo,, and N. Dioguardi. 1991. Hepatocellular carcinoma in Italian patients with cirrhosis [see comments]. N. Engl. J. Med. 325: 675 680.
46. Cribier, B.,, C. Schmitt,, A. Bingen, A. Kirn, and F. Keller. 1995. In vitro infection of peripheral blood mononuclear cells by hepatitis C virus. J. Gen. Virol. 76: 2485 2491.
47. D'Souza, E. D. A.,, K. Grace,, D. V. Sangar,, D. J. Rowlands,, and B. E. Clarke. 1995. In vitro cleavage of hepatitis C virus polyprotein substrates by purified recombinant NS3 protease. J. Gen. Virol. 76: 1729 1736.
48. De Mitri, M. S.,, K. Poussin,, P. Baccarini,, P. Pontisso,, A. D'Errico,, N. Simon,, W. Grigioni,, A. Alberti,, M. Beaugrand,, and E. Pisi. 1995. HCV-associated liver cancer without cirrhosis [see comments]. Lancet 345: 413 415.
49. Di Bisceglie, A. M.,, Z. D. Goodman,, K. G. Ishak,, J. H. Hoofnagle,, J. J. Melpolder,, and H. J. Alter. 1991. Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis. Hepatology 14: 969 974.
50. Diepolder, H. M.,, J.-T. Gerlach,, R. Zachoval,, R. M. Hoffmann,, M.-C. Jung,, E. A. Wierenga,, S. Scholz,, T. Santantonio,, M. Houghton,, S. Southwood,, A. Sette,, and G. R. Pape. 1997. Immunodominant CD4 + T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. J. Virol. 71: 6011 6019.
51. Diepolder, H. M.,, R. Zachoval,, R. M. Hoffmann,, E. A. Wierenga,, T. Santantonio,, M. C. Jung,, D. Eichenlaub,, and G. R. Pape. 1995. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346: 1006 1007.
52. Dittmann, S.,, M. Roggendorf,, J. Durkop,, M. Wiese,, B. Lorbeer,, and F. Deinhardt. 1991. Long-term persistence of hepatitis C virus antibodies in a single source outbreak. J. Hepatol. 13: 323 327.
53. Dusheiko, G.,, H. Schmilovitz-Weiss,, D. Brown,, F. McOmish,, P. L. Yap,, S. Sherlock,, N. Mclntyre,, and P. Simmonds. 1994. Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatology 19: 13 18.
54. Eckart, M. R.,, M. Selby,, F. Masiarz,, C. Lee,, K. Berger,, K. Crawford,, C. Kuo,, G. Kuo,, M. Houghton,, and Q. L. Choo. 1993. The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor. Biochem. Biophys. Res. Commun. 192: 399 406.
55. Enomoto, N.,, I. Sakuma,, Y. Asahina,, M. Kurosaki,, T. Murakami,, C. Yamamoto,, N. Izumi,, F. Marumo,, and C. Sato. 1995. Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus lb. Sensitivity to interferon is conferred by amino acid substitutions in the NS5A region. J. Clin. Invest. 96: 224 230.
56. Enomoto, N.,, I. Sakuma,, Y. Asahina,, M. Kurosaki,, T. Murakami,, C. Yamamoto,, Y. Ogura,, N. Izumi,, F. Marumo,, and C. Sato. 1996. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus lb infection. N. Engl. J. Med. 334: 77 81.
57. Failla, C.,, L. Tomei,, and R. De Francesco. 1994. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J. Virol. 68: 3753 3760.
58. Failla, C.,, L. Tomei,, and R. De Francesco. 1995. An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A. J. Virol. 69: 1769 1777.
59. Farci, P.,, H. J. Alter,, S. Govindarajan,, D. C. Wong,, R. Engle,, R. R. Lesniewski,, I. K. Mushahwar,, S. M. Desai,, R. H. Miller,, and N. Ogata. 1992. Lack of protective immunity against reinfection with hepatitis C virus. Science 258: 135 140.
60. Farci, P.,, H. J. Alter,, D. Wong,, R. H. Miller,, J. W. Shih,, B. Jett,, and R. H. Purcell. 1991. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis [see comments]. N. Engl. J. Med. 325: 98 104.
61. Farci, P.,, H. J. Alter,, D. C. Wong,, R. H. Miller,, S. Govindarajan,, R. Engle,, M. Shapiro,, and R. H. Purcell. 1994. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc. Natl. Acad. Sci. USA 91: 7792 7796.
62. Farci, P.,, A. Shimoda,, D. Wong,, T. Cabezon,, D. De Gioannis,, A. Strazera,, Y. Shimizu,, M. Shapiro,, H. J. Alter,, and R. H. Purcell. 1996. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc. Natl. Acad. Sci. USA 93: 15394 15399.
63. Fattovich, G.,, G. Giustina,, F. Degos,, F. Tremolada,, G. Diodati,, P. Almasio,, F. Nevens,, A. Solinas,, D. Mura,, J. T. Brouwer,, H. Thomas,, C. Njapoum,, C. Casarin,, P. Bonetti,, P. Fuschi,, J. Basho,, A. Tocco,, A. Bhalla,, R. Galassini,, F. Noventa,, S. W. Schalm,, and G. Realdi. 1997. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients [see comments]. Gastroenterology 112: 463 472.
64. Feinstone, S. M.,, H. J. Alter,, H. P. Dienes,, Y. Shimizu,, H. Popper,, D. Blackmore,, D. Sly,, W. T. London,, and R. H. Purcell. 1981. Non-A, non-B hepatitis in chimpanzees and marmosets. J. Infect. Dis. 144: 588 598.
65. Feinstone, S. M.,, A. Z. Kapikian,, R. H. Purcell,, H. J. Alter,, and P. V. Holland. 1975. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N. Engl. J. Med. 292: 767 770.
66. Feinstone, S. M.,, K. B. Mihalik,, T. Kamimura,, H. J. Alter,, W. T. London,, and R. H. Purcell. 1983. Inactivation of hepatitis B virus and non-A, non-B hepatitis by chloroform. Infect, Immun. 41: 816 821.
67. Ferrari, C.,, A. Valli,, L. Galati,, A. Penna,, P. Scaccaglia,, T. Giuberti,, C. Schianchi,, G. Missale,, M. G. Marin,, and F. Fiaccadori. 1994. T-cell response to structural and nonstructural hepatitis C virus antigens in persistent and self-limited hepatitis C virus infections. Hepatology 19: 286 295.
68. Finzi, D.,, M. Hermankova,, T. Pierson,, L. M. Carruth,, C. Buck,, R. E. Chaisson,, T. C. Quinn,, K. Chadwick,, J. Margolick,, R. Brookmeyer,, J. Gallant,, M. Markowitz,, D. D. Ho,, D. D. Richman,, and R. F. Siliciano. 1997. Identification of a reservoir for HIV-1 in patients of highly active antiretroviral therapy. Science 278: 1295 1300.
69. Garson, J. A.,, S. Brillanti, K. Whitby, M. Foli, R. Deaville, C. Masci, M. Miglioli, and L. Barbara. 1995. Analysis of clinical and virological factors associated with response to alpha interferon therapy in chronic hepatitis C. J. Med. Virol. 45: 348 353.
70. Gerber, M. A.,, Y. S. Shieh,, K. S. Shim,, S. N. Thung,, A. J. Demetris,, M. Schwartz,, G. Akyol,, and S. Dash. 1992. Detection of replicative hepatitis C virus sequences in hepatocellular carcinoma. Am. J. Pathol. 141: 1271 1277.
71. Gilliam, J. H., 3d, K. R. Geisinger, and J. E. Richter. 1984. Primary hepatocellular carcinoma after chronic non-A, non-B post-transfusion hepatitis. Ann. Intern. Med. 101: 794 795.
72. Grakoui, A.,, D. W. McCourt,, C. Wychowski,, S. M. Feinstone,, and C. M. Rice. 1993. A second hepatitis C virus-encoded proteinase. Proc. Natl. Acad. Sci. USA 90: 10583 10587.
73. Grakoui, A.,, D. W. McCourt,, C. Wychowski,, S. M. Feinstone,, and C. M. Rice. 1993. Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. J. Virol. 67: 2832 2843.
74. Grakoui, A.,, C. Wychowski,, C. Lin,, S. M. Feinstone,, and C. M. Rice. 1993. Expression and identification of hepatitis C virus polyprotein cleavage products. J. Virol. 67: 1385 1395.
75. Guidotti, L. G.,, T. Ishikawa,, M. V. Hobbs,, B. Matzke,, R. Schreiber,, and F. V. Chisari. 1996. Intracellular inactivation of the hepatitis C virus by cytotoxic T lymphocytes. Immunity 4: 25 36.
76. Gwack, Y.,, D. W. Kim,, J. H. Han,, and J. Choe. 1996. Characterization of RNA binding activity and RNA helicase activity of the hepatitis C virus NS3 protein. Biochem. Biophys. Res. Commun. 225: 654 659.
77. Hahm, B.,, D. S. Han,, S. H. Back,, O.-K. Song,, M.-J. Cho,, C.-J. Kim,, K. Shimotohno,, and S. K. Jang. 1995. NS3-4A of hepatitis C virus is a chymotrypsin-like protease. J. Virol. 69: 2534 2539.
78. Harada, S.,, Y. Watanabe,, K. Takeuchi,, T. Suzuki,, T. Katayama,, Y. Takebe,, I. Saito,, and T. Miyamura. 1991. Expression of processed core protein of hepatitis C virus in mammalian cells. J. Virol. 65: 3015 3021.
79. Haydon, G. H.,, L. M. Jarvis,, P. Simmonds,, D. J. Harrison,, O. J. Garden,, and P. C. Hayes. 1997. Association between chronic hepatitis C infection and hepatocellular carcinoma in a Scottish population. Gut 40: 128 132.
80. He, L. F.,, D. Ailing,, T. Popkin,, M. Shapiro,, H. J. Alter,, and R. H. Purcell. 1987. Determining the size of non-A, non-B hepatitis virus by filtration, J. Infect. Dis. 156: 636 640.
81. Hijikata, M.,, N. Kato,, Y. Ootsuyama,, M. Nakagawa,, S. Ohkoshi,, and K. Shimotohno. 1991. Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem. Biophys. Res. Commun. 175: 220 228.
82. Hijikata, 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 processing analysis. Proc. Natl. Acad. Sci. USA 88: 5547 5551.
83. Hijikata, M.,, H. Mizushima,, T. Akagi,, S. Mori,, N. Kakiuchi,, N. Kato,, T. Tanaka,, K. Kimura,, and K. Shimotohno. 1993. Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J. Virol. 67: 4665 4675.
84. Hijikata, M.,, H. Mizushima,, Y. Tanji,, Y. Komoda,, Y. Hirowatari,, T. Akagi,, N. Kato,, K. Kimura,, and K. Shimotohno. 1993. Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus. Proc. Natl. Acad. Sci. USA 90: 10773 10777.
85. Hijikata, M.,, Y. K. Shimizu,, H. Kato,, A. Iwamoto,, J. W. Shih,, H. J. Alter,, R. H. Purcell,, and H. Yoshikura. 1993. Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J. Virol. 67: 1953 1958.
86. Hino, K.,, S. Sainokami,, K. Shimoda,, S. Iino,, Y. Wang,, H. Okamoto,, Y. Miyakawa,, and M. Mayumi. 1994. Genotypes and titers of hepatitis C virus for predicting response to interferon in patients with chronic hepatitis C. J. Med. Virol. 42: 299 305.
87. Hiroishi, K.,, H. Kita,, M. Kojima,, H. Okamoto,, T. Moriyama,, T. Kaneko,, T. Ishi-kawa,, S. Ohnishi,, T. Aikawa,, N. Tanaka,, Y. Yazaki,, K. Mitamura,, and M. Imawari. 1997. Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection. Hepatology 25: 705 712.
88. Hirowatari, Y.,, M. Hijikata,, Y. Tanji,, H. Nyunoya,, H. Mizushima,, K. Kimura,, T. Tanaka,, N. Kato,, and K. Shimotohno. 1993. Two proteinase activities in HCV polypeptide expressed in insect cells using baculovirus vector. Arch. Virol. 133: 349 356.
89. Hoffmann, R. M.,, H. M. Diepolder,, R. Zachoval,, F. Zwiebel,, M.-C. Jung,, S. Scholz,, H. Nitschko,, G. Riethmuller,, and G. R. Pape. 1995. Mapping of immunodominant CD4 + Tlymphocyte epitope of hepatitis C virus antigens and their relevance during the course of chronic infection. Hepatology 21: 632 638.
90. Hollinger, F. B.,, G. L. Gitnick,, R. D. Aach,, W. Szmuness,, J. W. Mosley,, C. E. Stevens,, R. L. Peters,, J. M. Weiner,, J. B. Werch,, and J. J. Lander. 1978. Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group. Intervirology 10: 60 68.
91. 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.
92. Honda, M.,, S. Kaneko,, U. Masashi,, K. Kobayashi,, and S. Murakami. 1992. Sequence comparisons for a hepatitis C virus genome RNA isolated from a patient with liver cirrhosis. Gene 120: 317 318.
93. Honda, M.,, S. Kaneko,, A. Sakai,, M. Unoura,, S. Murakami,, and K. Kobayashi. 1994. Degree of diversity of hepatitis C virus quasispecies and progression of liver disease. Hepatology 20: 1144 1151.
94. Hong, Z.,, E. Ferrari,, J. Wright-Minogue,, R. Chase,, C. Risano,, G. Seelig,, C. G. Lee,, and A. D. Kwong. 1996. Enzymatic characterization of hepatitis C virus NS3/4A complexes expressed in mammalian cells by using the herpes simplex virus amplicon system. J. Virol. 70: 4261 4268.
95. Hopf, U.,, B. Moller,, D. Kuther,, R. Stemerowicz,, H. Lobeck,, A. Ludtke-Handjery,, E. Walter,, H. E. Blum,, M. Roggendorf,, and F. Deinhardt. 1990. Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV). J. Hepatol. 10: 69 76.
96. Iacovacci, S.,, A. Manzin,, S. Barca,, M. Sargiacomo,, A. Serafino,, M. B. Valli,, G. Macioce,, H. J. Hassan,, A. Ponzetto,, M. Clementi,, C. Peschle,, and G. Carloni. 1997. Molecular characterization and dynamics of hepatitis C virus replication in human fetal hepatocytes infected in vitro. Hepatology 26: 1328 1337.
97. Ide, Y.,, L. Zhang,, M. Chen,, G. Inchauspe,, C. Bahl,, Y. Sasaguri,, and R. Padmanab-han. 1996. Characterization of the nuclear localization signal and subcellular distribution of hepatitis C virus nonstructural protein NS5A. Gene 182: 203 211.
98. Inchauspe, G.,, S. Zebedee,, D.-H. Lee,, M. Sugitani,, M. Nasoff,, and A. M. Prince. 1991. Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates. Proc. Natl. Acad. Sci. USA 88: 10292 10296.
99. Iwata, K.,, T. Wakita,, A. Okumura,, K. Yoshioka,, M. Takayanagi,, J. R. Wands,, and S. Kakumu. 1995. Interferon gamma production by peripheral blood lymphocytes to hepatitis C virus core protein in chronic hepatitis C infection. Hepatology 22: 1057 1064.
100. Jackson, R. J.,, M. T. Howell,, and A. Kaminski. 1990. The novel mechanism of initiation of picornavirus RNA translation. Trends Biochem. Sci. 15: 477 483.
101. Jacob, J. R., K. H. Burk, J. W. Eichberg, G. R. Dreesman, and R. E. Lanford. 1990. Expression of infectious viral particles by primary chimpanzee hepatocytes isolated during the acute phase of non-A, non-B hepatitis. J. Infect. Dis. 161: 1121 1127.
102. Jin, Y.,, L. Fuller,, M. Carreno,, K. Zucker,, D. Roth,, V. Esquenazi,, T. Karatzas,, S. J. Swanson,, A. G. Tzakis,, and J. Miller. 1997. The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage. J. Clin. Immunol. 17: 140 153.
103. Kaito, M.,, S. Watanabe,, K. Tsukiyama-Kohara,, K. Yamaguchi,, Y. Kobayashi,, M. Konishi,, M. Yokoi,, S. Ishida,, S. Suzuki,, and M. Kohara. 1994. Hepatitis C virus particle detected by immunoelectron microscopic study, J. Gen. Virol. 75: 1755 1760.
104. Kaneko, T.,, I. Nakamura,, H. Kita,, K. Hiroishi,, T. Moriyama,, and M. Imawari. 1996. Three new cytotoxic T cell epitopes identified within the hepatitis C virus nucleoprotein. J. Gen. Virol. 77: 1305 1309.
105. Kanto, T.,, N. Hayashi,, T. Takehara,, H. Hagiwara,, E. Mita,, M. Oshita,, K. Katayama,, A. Kasahara,, H. Fusamoto,, and T. Kamada. 1995. Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alpha. J. Med. Virol. 46: 230 237.
106. 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 patents with non-A, non-B hepatitis. Proc. Natl. Acad. Sci. USA 87: 9524 9528.
107. Kato, N.,, T. Nakazawa,, T. Mizutani,, and K. Shimotohno. 1995. Susceptibility of human T-lymphotropic virus type I infected cell line MT-2 to hepatitis C virus infection. Biochem. Biophys. Res. Commun. 206: 863 869.
108. Kato, N.,, Y. Ootsuyama,, S. Ohkoshi,, T. Nakazawa,, H. Sekiya,, M. Hijikata,, and K. Shimotohno. 1992. Characterization of hypervariable regions in the putative envelope protein of hepatitis C virus. Biochem. Biophys. Res. Commun. 189: 119 127.
109. Kato, N.,, Y. Ootsuyama,, H. Sekiya,, S. Ohkoshi,, T. Nakazawa,, M. Hijikata,, and K. Shimotohno. 1994. Genetic drift in hypervariable region 1 of the viral genome in persistent hepatitis C virus infection. J. Virol. 68: 4776 4784.
110. Kato, N.,, Y. Ootsuyama,, T. Tanaka,, M. Nakagawa,, T. Nakazawa,, K. Muraiso,, S. Ohkoshi,, M. Hijikata,, and K. Shimotohno. 1992. Marked sequence diversity in the putative envelope proteins of hepatitis C viruses. Virus Res. 22: 107 123.
111. Kato, N.,, H. Sekiya,, Y. Ootsuyama,, T. Nakazawa,, M. Hijikata,, S. Ohkoshi,, and K. Shimotohno. 1993. Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus. J. Virol. 67: 3923 3930.
112. Kawamura, T.,, A. Furusaka,, M. J. Koziel,, R. T. Chung,, T. C. Wang,, E. V. Schmidt,, and T. J. Liang. 1997. Transgenic expression of hepatitis C virus structural proteins in the mouse. Hepatology 25: 1014 1021.
113. Khorsi, H.,, S. Castelain,, A. Wyseur,, J. Izopet,, V. Canva,, A. Rombout,, D. Capron,, J. P. Capron,, F. Lunel,, L. Stuyver,, and G. Duverlie. 1997. Mutations of hepatitis C virus lb NS5A 2209-2248 amino acid sequence do not predict the response to recombinant interferon-alfa therapy in French patients. J. Hepatol. 27: 72 77.
114. Kim, D. W.,, Y. Gwack,, J. H. Han,, and J. Choe. 1995. C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. Biochem. Biophys. Res. Commun. 215: 160 166.
115. Kim, D. W.,, Y. Gwack,, J. H. Han,, and J. Choe. 1997. Towards defining a minimal functional domain for NTPase and RNA helicase activities of the hepatitis C virus NS3 protein. Virus Res. 49: 17 25.
116. 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. (Erratum, Cell 89:159, 1997.)
117. Kita, H.,, K. Hiroishi,, T. Moriyama,, H. Okamoto,, T. Kaneko,, S. Ohnishi,, Y. Yazaki,, and M. Imawari. 1995. A minimal and optimal cytotoxic T cell epitope within hepatitis C virus nucleoprotein. J. Gen. Virol. 76: 3189 3193.
118. Kiyosawa, K.,, Y. Akahane,, A. Nagata,, Y. Koike,, and S. Furata. 1982. The significance of blood transfusion in non-A, non-B chronic liver disease in Japan. Vox Sang. 43: 45 52.
119. Kiyosawa, K.,, T. Sodeyama,, E. Tanaka,, Y. Gibo,, K. Yoshizawa,, Y. Nakano,, S. Furata,, Y. Akahane,, K. Nishioka,, and R. H. Purcell. 1990. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 12: 671 675.
120. Kobayashi, M.,, H. Kumada,, K. Chayama,, Y. Arase,, S. Saitou,, A. Tsubota,, I. Koida,, K. Ikeda,, M. Hashimoto,, and S. Iwasaki. 1994. Prevalence of HCV genotype among patients with chronic liver diseases in the Tokyo metropolitan area. J. Gastroenterol. 29: 583 587.
121. Koch, J. O.,, V. Lohmann,, U. HerIan,, and R. Bartenschlager. 1996. In vitro studies on the activation of the hepatitis C virus NS3 proteinase by the NS4A cofactor. Virology 221: 54 66.
122. Kolykhalov, A. A.,, E. V. Agapov,, K. J. Blight,, K. Mihalik,, S. M. Feinstone,, and C. M. Rice. 1997. Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277: 570 574.
123. 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.
124. Koonin, E. V. 1991. The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses. J. Gen. Virol. 72: 2197 2206.
125. Koretz, R. L.,, H. Abbey,, E. Coleman,, and G. Gitnick. 1993. Non-A, non-B posttransfusion hepatitis. Looking back in the second decade [see comments]. Ann. Intern. Med. 119: 110 115.
126. Koretz, R. L.,, S. C. Suffin,, and G. L. Gitnick. 1976. Post-transfusion chronic liver disease. Gastroenterology 71: 797 803.
127. Koziel, M. J.,, D. Dudley,, N. Afdhal,, Q.-L. Choo,, M. Houghton,, R. Ralston,, and B. D. Walker. 1993. Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J. Virol. 67: 7522 7532.
128. Koziel, M. J.,, D. Dudley,, N. Afdhal,, A. Grakoui, C. M. Rice, Q.-L. Choo, M. Houghton, and B. D. Walker. 1995. HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus. Identification of multiple epitopes and characterization of patterns of cytokine release. J. Clin. Invest. 96: 2311 2321.
129. Koziel, M. J.,, D. Dudley,, J. T. Wong,, J. Dienstag,, M. Houghton,, R. Ralston,, and B. D. Walker. 1992. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J. Immunol. 149: 3339 3344.
130. Kumar, U.,, J. Monjardino,, and H. C. Thomas. 1994. Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient [see comments]. Gastroenterology 106: 1072 1075.
131. Kuo, G.,, Q.-L. Choo,, H. J. Alter,, G. L. Gitnick,, A. G. Redeker,, R. H. Purcell,, T. Miyamura,, J. L. Dienstag,, M. J. Alter,, C. E. Stevens,, G. E. Tegtmeier,, F. Bonino,, M. Colombo,, W.-S. Lee,, C. Kuo,, K. Berger,, J. R. Shuster,, L. R. Overby,, D. W. Bradley,, and M. Houghton. 1989. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244: 362 364.
132. Kurosaki, M.,, N. Enomoto,, T. Murakami,, I. Sakuma,, Y. Asahina,, C. Yamamoto,, T. Ikeda,, S. Tozuka,, N. Izumi,, F. Maramo,, and C. Sato. 1997. Analysis of genotypes and amino acid residues 2209 to 2248 of the NS5A region of hepatitis C virus in relation to the response to interferon-beta therapy [see comments]. Hepatology 25: 750 753.
133. Lai, M. E.,, A. P. Mazzoleni,, F. Argiolu,, S. De Virgilis,, A. Balestrieri,, R. H. Purcell,, A. Cao,, and P. Farci. 1994. Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children. Lancet 343: 388 390.
134. Lanford, R. E.,, L. Notvall,, D. Chavez,, R. White,, G. Frenzel,, C. Simonsen,, and J. Kim. 1993. Analysis of hepatitis C virus capsid, E1, and E2/NS1 proteins expressed in insect cells. Virology 197: 225 235.
135. Lanford, R. E.,, C. Sureau,, J. R. Jacob,, R. White,, and T. R. Fuerst. 1994. Demonstration of in vitro infection of chimpanzee hepatocytes with hepatitis C virus using strand-specific RT/PCR. Virology 202: 606 614.
136. Lemm, J. A.,, T. Rumenapf,, E. G. Strauss,, J. H. Strauss,, and C. M. Rice. 1994. Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus and plus-strand RNA synthesis. EMBO J. 13: 2925 2934.
137. Lerat, H.,, F. Berby,, M. A. Trabaud,, O. Vidalin,, M. Major,, C. Trepo,, and G. In-chauspe. 1996. Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells. J. Clin. Invest. 97: 845 851.
138. Leroux-Roels, G.,, C. A. Esquivel,, R. DeLeys,, L. Stuyver,, A. Elewaut,, J. Philippe,, I. Desombere,, J. Paradijs,, and G. Maertens. 1996. Lymphoproliferative responses to hepatitis C virus core, E1, E2, and NS3 in patients with chronic hepatitis C infection treated with interferon alfa. Hepatology 23: 8 16.
139. Liaw, Y.-F.,, C.-S. Lee,, S. L. Tsai,, B.-W. Liaw,, T.-C. Chen,, I.-S. Sheen,, and C.-M. Chu. 1995. T-cell-mediated autologous hepatotoxicity in patients with chronic hepatitis C virus infection. Hepatology 22: 1368 1373.
140. Lin, C.,, B. D. Lindenbach,, B. M. Pragai,, D. W. McCourt,, and C. M. Rice. 1994. Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J. Virol. 68: 5063 5073.
141. Lin, C.,, B. M. Pragai,, A. Grakoui,, J. Xu,, and C. M. Rice. 1994. Hepatitis C virus NS3 serine proteinase: frans-cleavage requirements and processing kinetics. J. Virol. 68: 8147 8157.
142. Lin, C.,, J. A. Thomson,, and C. M. Rice. 1995. A central region in the hepatitis C virus NS4A protein allows formation of an active NS3-NS4A serine proteinase complex in vivo and in vitro. J. Virol. 69: 4373 4380.
143. Lo, S.-Y.,, M. J. Selby,, and J.-H. Ou. 1996. Interaction between hepatitis C virus core protein and El envelope protein. J. Virol. 70: 5177 5182.
144. Lo, S. Y.,, F. Masiarz,, S. B. Hwang,, M. M. Lai,, and J. H. Ou. 1995. Differential subcellular localization of hepatitis C virus core gene products. Virology 213: 455 461.
145. 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 NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 87: 331 342.
146. Mahaney, K.,, V. Tedeschi,, G. Maertens,, A. M. Di Bisceglie,, J. Vergalla,, J. H. Hoofnagle,, and R. Sallie. 1994. Genotypic analysis of hepatitis C virus in American patients [see comments]. Hepatology 20: 1405 1411.
147. Mannucci, P. M.,, M. Colombo,, and M. Rizzetto. 1982. Nonprogressive course of non-A, non-B chronic hepatitis in multitransfused hemophiliacs. Blood 60: 655 658.
148. Martell, M.,, J. I. Esteban,, J. Quer,, J. Genesca,, A. J. Weiner,, R. Esteban,, J. Guardia,, and J. Gomez. 1992. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J. Virol. 66: 3225 3229.
149. Martinot-Peignoux, M.,, P. Marcellin,, M. Pouteau,, C. Castelnau,, N. Boyer,, M. Poliquin,, C. Degott,, I. Descombes,, V. LeBreton,, and V. Milotova. 1995. Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology 22: 1050 1056.
150. Mazzanti, R.,, L. Messerini,, L. Monsacchi,, G. Buzzelli,, A. L. Zignego,, M. Foschi,, M. Monti,, G. Laffi,, L. Morbidelli,, O. Fantappie,, F. Bartoloni Saint Omer,, and M. Ziche. 1997. Chronic viral hepatitis induced by hepatitis C but not hepatitis B virus infection correlates with increased liver angiogenesis. Hepatology 25: 229 234.
151. McMichael, A. J.,, F. M. Gotch,, G. R. Noble,, and P. A. Beare. 1983. Cytotoxic T-cell immunity to influenza. N. Engl. J. Med. 309: 13 17.
152. McOmish, F.,, P. L. Yap,, B. C. Dow,, E. A. Follett,, C. Seed,, A. J. Keller,, T. J. Cobain,, T. Krusius,, E. Kolho,, and R. Naukkarinen. 1994. Geographical distribution of hepatitis C virus genotypes in blood donors: an international collaborative survey. J. Clin. Microbiol. 32: 884 892.
153. Miller, R. H.,, and R. H. Purcell. 1990. Hepatitis C virus shares amino acid sequence similarity with pestivirus and flavivirus as well as members of two plant virus supergroups. Proc. Natl. Acad. Sci. USA 87: 2057 2061.
154. Minutello, M. A.,, P. Pileri,, D. Unutmaz,, S. Censini,, G. Kuo,, M. Houghton,, F. Bonino,, and S. Abrignani. 1993. Compartmentalization of T lymphocytes to the site of disease: intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C. J. Exp. Med. 178: 17 25.
155. Missale, G.,, R. Bertoni,, V. Lamonaca,, A. Valli,, M. Massari,, C. Mori,, M. G. Rumi,, M. Houghton,, F. Fiaccadori,, and C. Ferrari. 1996. Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response, J. Clin. Invest. 98: 706 714.
156. Mitsui, T.,, K. Iwano,, K. Masuko,, C. Yamazaki,, H. Okamoto,, F. Tsuda,, T. Tanaka,, and S. Mishiro. 1992. Hepatitis C virus infection in medical personnel after needlestick accident [see comments]. Hepatology 16: 1109 1114.
157. Mizushima, H.,, M. Hijikata,, S. Asabe,, M. Hirota,, K. Kimura,, and K. Shimotohno. 1994. Two hepatitis C virus glycoprotein E2 products with different C termini. J. Virol. 68: 6215 6222.
158. Mizutani, T.,, N. Kato,, M. Ikeda,, K. Sugiyama,, and K. Shimotohno. 1996. Long-term human T-cell culture system supporting hepatitis c virus replication. Biochem. Biophys. Res. Commun. 227: 822 826.
159. Moradpour, D.,, C. Englert,, T. Wakita,, and J. R. Wands. 1996. Characterization of cell lines allowing tightly regulated expression of hepatitis C virus core protein. Virology 222: 51 63.
160. Moriya, K.,, H. Yotsuyanagi,, Y. Shintani,, H. Fujie,, K. Ishibashi,, Y. Matsuura,, T. Miyamura,, and K. Koike. 1997. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J. Gen. Virol. 78: 1527 1531.
161. Muramatsu, S.,, S. Ishido,, T. Fujita,, M. Itoh,, and H. Hotta. 1997. Nuclear localization of the NS3 protein of hepatitis C virus and factors affecting the localization. J. Virol. 71: 4954 4961.
162. Nagayama, R.,, F. Tsuda,, H. Okamoto,, Y. Wang,, T. Mitsui,, T. Tanaka,, Y. Miyakawa,, and M. Mayumi. 1993. Genotype dependence of hepatitis C virus antibodies detectable by the first-generation enzyme-linked immunosorbent assay with C100-3 protein. J. Clin. Invest. 92: 1529 1533.
163. Nakajima, N.,, M. Hijikata,, H. Yoshikura,, and Y. K. Shimizu. 1996. Characterization of long-term cultures of hepatitis C virus. J. Virol. 70: 3325 3329.
164. Nakao, H.,, H. Okamoto,, H. Tokita,, T. Inoue,, H. Iizuka,, G. Pezzato,, and S. Mishiro. 1996. Full-length genomic sequence of a hepatitis C virus genotype 2c isolate (BEBE1) and the 2c-specific PCR primers. Arch. Virol. 141: 701 704.
165. Nakazawa, T.,, N. Kato,, Y. Ootsuyama,, H. Sekiya,, T. Fujioka,, A. Shibuya,, and K. Shimotohno. 1994. Genetic alteration of the hepatitis C virus hypervariable region obtained from an asymptomatic carrier. Int. J. Cancer 56: 204 207.
166. Nelson, D. R.,, C. G. Marousis,, G. L. Davis,, K. M. Rice,, J. T. Wong,, M. Houghton,, and J. Y. N. Lau. 1997. The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. J. Immunol. 158: 1473 1481.
167. Nishihara, T.,, C. Nozaki,, H. Nakatake, K. Hoshiko, M. Esumi, N. Hayashi, K. Hino, F. Hamada, K. Mizuno, and T. Shikata. 1993. Secretion and purification of hepatitis C virus NS1 glycoprotein produced by recombinant baculovirus-infected insect cells. Gene 129: 207 214.
168. Nishioka, K.,, J. Watanabe,, S. Furata,, E. Tanaka,, S. Iino,, H. Suzuki,, T. Tsuji,, M. Yano,, G. Kuo,, and Q. L. Choo. 1991. A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan. Cancer 67: 429 433.
169. Odeberg, J.,, Z. Yun,, A. Sonnerborg,, K. Bjoro,, M. Uhlen,, and J. Lundeberg. 1997. Variation of hepatitis C virus hypervariable region 1 in immunocompromised patients. J. Infect. Dis. 175: 938 943.
170. Okamoto, H.,, N. Kanai,, and S. Mishiro. 1992. Full-length nucleotide sequence of a Japanese hepatitis C virus isolate (HC-J1) with high homology to USA isolates. Nucleic Acids Res. 20: 6410.
171. Okamoto, H.,, M. Kojima,, S.-I. Okada,, H. Yoshizawa,, H. Iizuka,, T. Tanaka,, E. E. Muchmore,, D. A. Paterson,, Y. Ito,, and S. Mishiro. 1992. Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability. Virology 190: 894 899.
172. Okamoto, H.,, K. Kurai,, S. Okada,, K. Yamamoto,, H. Lizuka,, T. Tanaka,, S. Fukuda,, F. Tsuda,, and S. Mishiro. 1992. Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology 188: 331 341.
173. Okamoto, H.,, S. Okada,, Y. Sugiyama,, K. Kurai,, H. Iizuka,, A. Machida,, Y. Miyakawa,, and M. Mayumi. 1991. Nucleotide sequence of the genomic RNA of hepatitis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions. J. Gen. Virol. 72: 2697 2704.
174. Okamoto, H.,, S. Okada,, Y. Sugiyama,, T. Tanaka,, Y. Sugai,, Y. Akahane,, A. Machida,, S. Mishiro,, H. Yoshizawa,, and Y. Miyakawa. 1990. Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5'-noncoding region. Jpn. J. Exp. Med. 60: 215 222.
175. Pateron, D.,, N. Ganne,, J. C. Trinchet,, M. H. Aurosseau,, F. Mal,, C. Meicler,, E. Coderc,, P. Reboullet,, and M. Beaugrand. 1994. Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis [see comments], J. Hepatol. 20: 65 71.
176. Pieroni, L.,, E. Santolini,, C. Fipaldini,, L. Pacini,, G. Migliaccio,, and N. La Monica. 1997. In vitro study of the NS2-3 protease of hepatitis C virus. J. Virol. 71: 6373 6380.
177. Pilipenko, E. V.,, A. P. Gmyl,, S. V. Maslova,, Y. V. Svitkin,, A. N. Sinyakov,, and V. I. Agol. 1992. Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell 68: 119 131.
178. Pistello, M.,, F. Maggi,, L. Vatteroni,, N. Cecconi,, F. Panicucci,, G. P. Bresci,, L. Gambardella,, M. Taddei,, A. Bionda,, and M. Tuoni. 1994. Prevalence of hepatitis C virus genotypes in Italy. J. Clin. Microbiol. 32: 232 234.
179. Poch, O.,, I. Sauvaget,, M. Delarue,, and N. Tordo. 1989. Identification of four conserved motifs among the RNA dependent polymerase encoding elements. EMBO J. 8: 3867 3874.
180. Power, J. P.,, E. Lawlor,, F. Davidson,, E. C. Holmes,, P. L. Yap,, and P. Simmonds. 1995. Molecular epidemiology of an outbreak of infection with hepatitis C virus in recipients of anti-D immunoglobulin [see comments]. Lancet 345: 1211 1213.
181. Pozzato, G.,, M. Moretti,, F. Franzin,, L. S. Croce,, C. Tiribelli,, T. Masayu,, S. Kaneko,, M. Unoura,, and K. Kobayashi. 1991. Severity of liver disease with different hepatitis C viral clones. Lancet 338: 509. (Letter.)
182. Prince, A. M.,, B. Brotman,, G. F. Grady,, W. J. Kuhns,, C. Hazzi,, R. W. Levine,, and S. J. Millian. 1974. Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus. Lancet 2: 241 246.
183. Qu, D.,, J. S. Li,, L. Vitvitski,, S. Mechai,, F. Berby,, S. P. Tong,, F. Bailly,, Q. S. Wang,, J. L. Martin,, and C. Trepo. 1994. Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II. J. Hepatol. 21: 70 75.
184. Ralston, R.,, K. Thudium,, K. Berger,, C. Kuo,, B. Gervase,, J. Hall,, M. Selby,, G. Kuo,, M. Houghton,, and Q.-L. Choo. 1993. Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses. J. Virol. 67: 6753 6761.
185. Ray, R. B.,, L. M. Lagging,, K. Meyer,, and R. Ray. 1996. Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J. Virol. 70: 4438 4443.
186. Ray, R. B.,, L. M. Lagging,, K. Meyer,, R. Steele,, and R. Ray. 1995. Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein. Virus Res. 37: 209 220.
187. Ray, R. B.,, K. Meyer,, and R. Ray. 1996. Suppression of apoptotic cell death by hepatitis C virus core protein. Virology 226: 176 182.
188. Ray, R. B.,, R. Steele,, K. Meyer,, and R. Ray. 1997. Transcriptional repression of p53 promoter by hepatitis C virus core protein. J. Biol. Chem. 272: 10983 10986.
189. Realdi, G.,, A. Alberti,, M. Rugge,, A. M. Rigoli,, F. Tremolada,, L. Schivazappa,, and A. Ruol. 1982. Long-term follow-up of acute and chronic non-A, non-B posttransfusion hepatitis: evidence of progression to liver cirrhosis. Gut 23: 270 275.
190. Reed, K. E.,, J. Xu,, and C. M. Rice. 1997. Phosphorylation of the hepatitis C virus NS5A protein in vitro and in vivo: properties of the NS5A-associated kinase. J. Virol. 71: 7187 7197.
191. Rehermann, B.,, K.-M. Chang,, J. G. McHutchison,, R. Kokka,, M. Houghton,, and F. V. Chisari. 1996. Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection. J. Clin. Invest. 98: 1432 1440.
192. Rehermann, B.,, K.-M. Chang,, J. G. McHutchison,, R. Kokka,, M. Houghton,, C. M. Rice,, and F. V. Chisari. 1996. Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. J. Virol. 70: 7092 7102.
193. Rice, C. M., 1996. Flaviviridae: the viruses and their replication, p. 931 960. In B. N. Fields,, D. M. Knipe,, and P. M. Howley (ed.), Fields Virology, 3rd ed. Raven Press, New York.
194. Rosa, D.,, S. Campagnoli,, C. Moretto,, E. Guenzi,, L. Cousens,, M. Chin,, C. Dong,, A. J. Weiner,, J. Y. Lau,, Q.-L. Choo,, D. Chien,, P. Pileri,, M. Houghton,, and S. Abrignani. 1996. A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc. Natl. Acad. Sci. USA 93: 1759 1763.
195. Saito, I.,, T. Miyamura,, A. Ohbayashi,, H. Harada,, T. Katayama,, S. Kikuchi,, Y. Watanabe,, S. Koi,, M. Onji,, and Y. Ohta. 1990. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 87: 6547 6549.
196. Saito, K.,, D. Sullivan,, Y. Haruna,, N. D. Theise,, S. N. Thung,, and M. A. Gerber. 1997. Detection of hepatitis C virus RNA sequences in hepatocellular carcinoma and its precursors by microdissection polymerase chain reaction. Arch. Pathol. Lab. Med. 121: 400 403.
197. Saito, S.,, N. Kato,, M. Hijikata,, T. Gunji,, M. Itabashi,, M. Kondo,, K. Tanaka, and K. Shimotohno. 1996. Comparison of hypervariable regions (HVR1 and HVR2) in positive-and negative-stranded hepatitis C virus RNA in cancerous and non-cancerous liver tissue, peripheral blood mononuclear cells and serum from a patient with hepatocellular carcinoma. Int. J. Cancer 67: 199 203.
198. Sakamuro, D.,, T. Furukawa,, and T. Takegami. 1995. Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. J. Virol. 69: 3893 3896.
199. Santolini, E.,, G. Migliaccio,, and N. La Monica. 1994. Biosynthesis and biochemical properties of the hepatitis C virus core protein. J. Virol. 68: 3631 3641.
200. Sato, C.,, and N. Enomoto. 1996. Specific hepatitis C virus NS5A sequences determine the outcome of interferon treatment. Gastroenterology 111: 1152 1154.
201. Sato, K.,, H. Okamoto,, S. Aihara,, Y. Hoshi,, T. Tanaka,, and S. Mishiro. 1993. Demonstration of sugar moiety on the surface of hepatitis C virions recovered from the circulation of infected humans. Virology 196: 354 357.
202. Satoh, S.,, Y. Tanji,, M. Hijikata,, K. Kimura,, and K. Shimotohno. 1995. The N-terminal region of hepatitis C virus nonstructural protein 3 (NS3) is essential for stable complex formation with NS4A. J. Virol. 69: 4255 4260.
203. Schalm, S. W.,, B. E. Hansen,, L. Chemello,, A. Bellobuono,, J. T. Brouwer,, O. Weiland,, L. Cavalletto,, R. Schvarcz,, G. Ideo,, and A. Alberti. 1997. Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers. J. Hepatol. 26: 961 966.
204. Schmidt, W. N.,, P. Wu,, J. Cederna,, F. A. Mitros,, D. R. LaBrecque,, and J. T. Stapleton. 1997. Surreptitious hepatitis C virus (HCV) infection detected in the majority of patients with cryptogenic chronic hepatitis and negative HCV antibody tests. J. Infect. Dis. 176: 27 33.
205. Seeff, L. B.,, Z. Buskell-Bales,, E. C. Wright,, S. J. Durako,, H. J. Alter,, F. L. Iber,, F. B. Hollinger,, G. L. Gitnick,, R. G. Knodell,, R. P. Perrillo,, C. E. Stevens,, and C. G. Hollingsworth. 1992. Long-term mortality after transfusion-associated non-A, non-B hepatitis. N. Engl. J. Med. 327: 1906 1911.
206. Sekiya, H.,, N. Kato,, Y. Ootsuyama,, T. Nakazawa,, K. Yamauchi,, and K. Shimotohno. 1994. Genetic alterations of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis: humoral immune response to hypervariable region 1. Int. J. Cancer 57: 664 670.
207. Selby, M. J.,, Q.-L. Choo,, K. Berger,, G. Kuo,, E. Glazer,, M. Eckart,, C. Lee,, D. Chien,, C. Kuo,, and M. Houghton. 1993. Expression, identification and subcellular localization of the proteins encoded by the hepatitis C viral genome. J. Gen. Virol. 74: 1103 1113.
208. Selby, M. J.,, E. Glazer,, F. Masiarz,, and M. Houghton. 1994. Complex processing and protein: protein interactions in the E2: NS2 region of HCV. Virology 204: 114 122.
209. Shieh, Y. S.,, C. Nguyen,, M. V. Vocal,, and H. W. Chu. 1993. Tumor-suppressor p53 gene in hepatitis A and B virus-associated human hepatocellular carcinoma. Int. J. Cancer 54: 558 562.
210. Shih, J. W.,, J. I. Mur,, and H. J. Alter. 1986. Non-A, non-B hepatitis: advances and unfulfilled expectations of the first decade. Prog. Liver Dis. 8: 433 452.
211. Shimizu, Y. K.,, S. M. Feinstone,, M. Kohara,, R. H. Purcell,, and H. Yoshikura. 1996. Hepatitis C virus: detection of intracellular virus particles by electron microscopy [see comments]. Hepatology 23: 205 209.
212. Shimizu, Y. K.,, M. Hijikata,, A. Iwamoto,, H. J. Alter,, R. H. Purcell,, and H. Yoshikura. 1994. Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J. Virol. 68: 1494 1500.