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Submitted on April 25, 2005
Accepted on May 31, 2005
Complete Replication of Hepatitis C Virus in Cell Culture
Brett D. Lindenbach 1, Matthew J. Evans 1, Andrew J. Syder 1, Benno Wölk 1, Timothy L. Tellinghuisen 1, Christopher C. Liu 2, Toshiaki Maruyama 3, Richard O. Hynes 2, Dennis R. Burton 4, Jane A. McKeating 5, Charles M. Rice 1*
1 Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. 2 Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 3 Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Present address: Alexion Antibody Technologies, San Diego, CA 92121, USA. 4 Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 5 Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA; Present address: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, UK.
* To whom correspondence should be addressed.
Charles M. Rice , E-mail: ricec{at}rockefeller.edu
Many aspects of the hepatitis C virus (HCV) life cycle havenot been reproduced in cell culture, which has slowed researchprogress on this important human pathogen. Here we describea full-length HCV genome that replicates and produces virusparticles that are infectious in cell culture (HCVcc). Replicationof HCVcc was robust, producing nearly 105 infectious units/mlwithin 48 hours. Virus particles were filterable and neutralizedwith a monoclonal antibody against the viral glycoprotein E2.Viral entry was dependent on cellular expression of a putativeHCV receptor, CD81. HCVcc replication was inhibited by interferon-and by several HCV-specific antiviral compounds, suggestingthat this in vitro system will aid in the search for improvedantivirals.
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89, 653-659
|Abstract »|Full Text »|PDF »
Hepatitis C Virus Genotype 1a Growth and Induction of Autophagy.
M. Ait-Goughoulte, T. Kanda, K. Meyer, J. S. Ryerse, R. B. Ray, and R. Ray (2008)
J. Virol.
82, 2241-2249
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Visualization of Double-Stranded RNA in Cells Supporting Hepatitis C Virus RNA Replication.
P. Targett-Adams, S. Boulant, and J. McLauchlan (2008)
J. Virol.
82, 2182-2195
|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 »
Hepatitis C Virus Entry.
T. von Hahn and C. M. Rice (2008)
J. Biol. Chem.
283, 3689-3693
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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
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Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization.
T. K. H. Scheel, J. M. Gottwein, T. B. Jensen, J. C. Prentoe, A. M. Hoegh, H. J. Alter, J. Eugen-Olsen, and J. Bukh (2008)
PNAS
105, 997-1002
|Abstract »|Full Text »|PDF »
Isolation and Characterization of Broadly Neutralizing Human Monoclonal Antibodies to the E1 Glycoprotein of Hepatitis C Virus.
J.-C. Meunier, R. S. Russell, V. Goossens, S. Priem, H. Walter, E. Depla, A. Union, K. N. Faulk, J. Bukh, S. U. Emerson, et al. (2008)
J. Virol.
82, 966-973
|Abstract »|Full Text »|PDF »
Identification of a Broadly Cross-Reacting and Neutralizing Human Monoclonal Antibody Directed against the Hepatitis C Virus E2 Protein.
M. Perotti, N. Mancini, R. A. Diotti, A. W. Tarr, J. K. Ball, A. Owsianka, R. Adair, A. H. Patel, M. Clementi, and R. Burioni (2008)
J. Virol.
82, 1047-1052
|Abstract »|Full Text »|PDF »
Serum-Derived Hepatitis C Virus Infection of Primary Human Hepatocytes Is Tetraspanin CD81 Dependent.
S. Molina, V. Castet, L. Pichard-Garcia, C. Wychowski, E. Meurs, J.-M. Pascussi, C. Sureau, J.-M. Fabre, A. SaCunha, D. Larrey, et al. (2008)
J. Virol.
82, 569-574
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3' RNA Elements in Hepatitis C Virus Replication: Kissing Partners and Long Poly(U).
Effect of Cell Polarization on Hepatitis C Virus Entry.
C. J. Mee, J. Grove, H. J. Harris, K. Hu, P. Balfe, and J. A. McKeating (2008)
J. Virol.
82, 461-470
|Abstract »|Full Text »|PDF »
The Lipid Droplet Binding Domain of Hepatitis C Virus Core Protein Is a Major Determinant for Efficient Virus Assembly.
A. Shavinskaya, S. Boulant, F. Penin, J. McLauchlan, and R. Bartenschlager (2007)
J. Biol. Chem.
282, 37158-37169
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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 »
TBC1D20 Is a Rab1 GTPase-activating Protein That Mediates Hepatitis C Virus Replication.
E. H. Sklan, R. L. Serrano, S. Einav, S. R. Pfeffer, D. G. Lambright, and J. S. Glenn (2007)
J. Biol. Chem.
282, 36354-36361
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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 »
Claudin-6 and Claudin-9 Function as Additional Coreceptors for Hepatitis C Virus.
A. Zheng, F. Yuan, Y. Li, F. Zhu, P. Hou, J. Li, X. Song, M. Ding, and H. Deng (2007)
J. Virol.
81, 12465-12471
|Abstract »|Full Text »|PDF »
Norwalk Virus RNA Is Infectious in Mammalian Cells.
S. Guix, M. Asanaka, K. Katayama, S. E. Crawford, F. H. Neill, R. L. Atmar, and M. K. Estes (2007)
J. Virol.
81, 12238-12248
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An influenza virus replicon system in yeast identified Tat-SF1 as a stimulatory host factor for viral RNA synthesis.
T. Naito, Y. Kiyasu, K. Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata (2007)
PNAS
104, 18235-18240
|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
|Abstract »|Full Text »|PDF »