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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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   Abstract »    Full Text »    PDF »
A virocidal amphipathic {alpha}-helical peptide that inhibits hepatitis C virus infection in vitro.
G. Cheng, A. Montero, P. Gastaminza, C. Whitten-Bauer, S. F. Wieland, M. Isogawa, B. Fredericksen, S. Selvarajah, P. A. Gallay, M. R. Ghadiri, et al. (2008)
PNAS 105, 3088-3093
   Abstract »    Full Text »    PDF »
NS3 Peptide, a Novel Potent Hepatitis C Virus NS3 Helicase Inhibitor: Its Mechanism of Action and Antiviral Activity in the Replicon System.
A. Gozdek, I. Zhukov, A. Polkowska, J. Poznanski, A. Stankiewicz-Drogon, J. M. Pawlowicz, W. Zagorski-Ostoja, P. Borowski, and A. M. Boguszewska-Chachulska (2008)
Antimicrob. Agents Chemother. 52, 393-401
   Abstract »    Full Text »    PDF »
Novel Chimeric Genotype 1b/2a Hepatitis C Virus Suitable for High-Throughput Screening.
Y. Zhang, P. Weady, R. Duggal, and W. Hao (2008)
Antimicrob. Agents Chemother. 52, 666-674
   Abstract »    Full Text »    PDF »
Identification of Residues Required for RNA Replication in Domains II and III of the Hepatitis C Virus NS5A Protein.
T. L. Tellinghuisen, K. L. Foss, J. C. Treadaway, and C. M. Rice (2008)
J. Virol. 82, 1073-1083
   Abstract »    Full Text »    PDF »
Identification of Human Kinases Involved in Hepatitis C Virus Replication by Small Interference RNA Library Screening.
L. Supekova, F. Supek, J. Lee, S. Chen, N. Gray, J. P. Pezacki, A. Schlapbach, and P. G. Schultz (2008)
J. Biol. Chem. 283, 29-36
   Abstract »    Full Text »    PDF »
Phenotypic Characterization of Resistant Val36 Variants of Hepatitis C Virus NS3-4A Serine Protease.
Y. Zhou, D. J. Bartels, B. L. Hanzelka, U. Muh, Y. Wei, H.-M. Chu, A. M. Tigges, D. L. Brennan, B. G. Rao, L. Swenson, et al. (2008)
Antimicrob. Agents Chemother. 52, 110-120
   Abstract »    Full Text »    PDF »
3' RNA Elements in Hepatitis C Virus Replication: Kissing Partners and Long Poly(U).
S. You and C. M. Rice (2008)
J. Virol. 82, 184-195
   Abstract »    Full Text »    PDF »
DDX3 DEAD-Box RNA Helicase Is Required for Hepatitis C Virus RNA Replication.
Y. Ariumi, M. Kuroki, K.-i. Abe, H. Dansako, M. Ikeda, T. Wakita, and N. Kato (2007)
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
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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
   Abstract »    Full Text »    PDF »
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
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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
   Abstract »    Full Text »    PDF »


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