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Science 2 July 1999:
Vol. 285. no. 5424, pp. 110 - 113
DOI: 10.1126/science.285.5424.110
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Reports

Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line

V. Lohmann, 1 F. Körner, 1 J.-O. Koch, 1 U. Herian, 1 L. Theilmann, 2 R. Bartenschlager 1*

An estimated 170 million persons worldwide are infected with hepatitis C virus (HCV), a major cause of chronic liver disease. Despite increasing knowledge of genome structure and individual viral proteins, studies on virus replication and pathogenesis have been hampered by the lack of reliable and efficient cell culture systems. A full-length consensus genome was cloned from viral RNA isolated from an infected human liver and used to construct subgenomic selectable replicons. Upon transfection into a human hepatoma cell line, these RNAs were found to replicate to high levels, permitting metabolic radiolabeling of viral RNA and proteins. This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies of HCV and the development of antiviral drugs.

1 Institute for Virology, Johannes-Gutenberg University Mainz, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany.
2 Städtisches Klinikum Pforzheim, Medizinische Klinik II, 75116 Pforzheim, Germany.
*   To whom correspondence should be addressed. E-mail: bartnsch{at}mail.uni-mainz.de

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J. Virol. 81, 13922-13926
   Abstract »    Full Text »    PDF »
Human Apolipoprotein E Is Required for Infectivity and Production of Hepatitis C Virus in Cell Culture.
K.-S. Chang, J. Jiang, Z. Cai, and G. Luo (2007)
J. Virol. 81, 13783-13793
   Abstract »    Full Text »    PDF »
Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response.
M. Tasaka, N. Sakamoto, Y. Itakura, M. Nakagawa, Y. Itsui, Y. Sekine-Osajima, Y. Nishimura-Sakurai, C.-H. Chen, M. Yoneyama, T. Fujita, et al. (2007)
J. Gen. Virol. 88, 3323-3333
   Abstract »    Full Text »    PDF »
Cell Culture Adaptation of Hepatitis C Virus and In Vivo Viability of an Adapted Variant.
A. Kaul, I. Woerz, P. Meuleman, G. Leroux-Roels, and R. Bartenschlager (2007)
J. Virol. 81, 13168-13179
   Abstract »    Full Text »    PDF »
Responses of Nontransformed Human Hepatocytes to Conditional Expression of Full-Length Hepatitis C Virus Open Reading Frame.
W. Tang, C. A. Lazaro, J. S. Campbell, W. T. Parks, M. G. Katze, and N. Fausto (2007)
Am. J. Pathol. 171, 1831-1846
   Abstract »    Full Text »    PDF »
Inhibition of hepatitis C virus replication by peroxidation of arachidonate and restoration by vitamin E.
H. Huang, Y. Chen, and J. Ye (2007)
PNAS 104, 18666-18670
   Abstract »    Full Text »    PDF »
Characterization of Hepatitis C Virus Deletion Mutants Circulating in Chronically Infected Patients.
S. Noppornpanth, S. L. Smits, T. X. Lien, Y. Poovorawan, A. D. M. E. Osterhaus, and B. L. Haagmans (2007)
J. Virol. 81, 12496-12503
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Anti-hepatitis C Virus Activity of Tamoxifen Reveals the Functional Association of Estrogen Receptor with Viral RNA Polymerase NS5B.
K. Watashi, D. Inoue, M. Hijikata, K. Goto, H. H. Aly, and K. Shimotohno (2007)
J. Biol. Chem. 282, 32765-32772
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Identification of Novel Small-Molecule Inhibitors of West Nile Virus Infection.
A. O. Noueiry, P. D. Olivo, U. Slomczynska, Y. Zhou, B. Buscher, B. Geiss, M. Engle, R. M. Roth, K. M. Chung, M. Samuel, et al. (2007)
J. Virol. 81, 11992-12004
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The Imidazopyrrolopyridine Analogue AG110 Is a Novel, Highly Selective Inhibitor of Pestiviruses That Targets the Viral RNA-Dependent RNA Polymerase at a Hot Spot for Inhibition of Viral Replication.
J. Paeshuyse, J.-M. Chezal, M. Froeyen, P. Leyssen, H. Dutartre, R. Vrancken, B. Canard, C. Letellier, T. Li, H. Mittendorfer, et al. (2007)
J. Virol. 81, 11046-11053
   Abstract »    Full Text »    PDF »
Nuclear factors are involved in hepatitis C virus RNA replication.
O. Isken, M. Baroth, C. W. Grassmann, S. Weinlich, D. H. Ostareck, A. Ostareck-Lederer, and S.-E. Behrens (2007)
RNA 13, 1675-1692
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Endoribonuclease-Prepared Short Interfering RNAs Induce Effective and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication.
M. Gimenez-Barcons, B. Clotet, and M. A. Martinez (2007)
J. Virol. 81, 10680-10686
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Bile Acids Promote the Expression of Hepatitis C Virus in Replicon-Harboring Cells.
K.-O. Chang and D. W. George (2007)
J. Virol. 81, 9633-9640
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Robust production of infectious viral particles in Huh-7 cells by introducing mutations in hepatitis C virus structural proteins.
D. Delgrange, A. Pillez, S. Castelain, L. Cocquerel, Y. Rouille, J. Dubuisson, T. Wakita, G. Duverlie, and C. Wychowski (2007)
J. Gen. Virol. 88, 2495-2503
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Studying Hepatitis C Virus: Making the Best of a Bad Virus.
T. L. Tellinghuisen, M. J. Evans, T. von Hahn, S. You, and C. M. Rice (2007)
J. Virol. 81, 8853-8867
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Hepatitis C Virus p7 and NS2 Proteins Are Essential for Production of Infectious Virus.
C. T. Jones, C. L. Murray, D. K. Eastman, J. Tassello, and C. M. Rice (2007)
J. Virol. 81, 8374-8383
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Phenotypic and Structural Analyses of Hepatitis C Virus NS3 Protease Arg155 Variants: SENSITIVITY TO TELAPREVIR (VX-950) AND INTERFERON {alpha}.
Y. Zhou, U. Muh, B. L. Hanzelka, D. J. Bartels, Y. Wei, B. G. Rao, D. L. Brennan, A. M. Tigges, L. Swenson, A. D. Kwong, et al. (2007)
J. Biol. Chem. 282, 22619-22628
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The NS3 Helicase and NS5B-to-3'X Regions Are Important for Efficient Hepatitis C Virus Strain JFH-1 Replication in Huh7 Cells.
A. Murayama, T. Date, K. Morikawa, D. Akazawa, M. Miyamoto, M. Kaga, K. Ishii, T. Suzuki, T. Kato, M. Mizokami, et al. (2007)
J. Virol. 81, 8030-8040
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Cellular cofactors affecting hepatitis C virus infection and replication.
G. Randall, M. Panis, J. D. Cooper, T. L. Tellinghuisen, K. E. Sukhodolets, S. Pfeffer, M. Landthaler, P. Landgraf, S. Kan, B. D. Lindenbach, et al. (2007)
PNAS 104, 12884-12889
   Abstract »    Full Text »    PDF »
Binding Dynamics of Hepatitis C Virus' NS5A Amphipathic Peptide to Cell and Model Membranes.
N.-J. Cho, K. H. Cheong, C. Lee, C. W. Frank, and J. S. Glenn (2007)
J. Virol. 81, 6682-6689
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