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Originally published in Science Express on 9 June 2005
Science 22 July 2005:
Vol. 309. no. 5734, pp. 623 - 626
DOI: 10.1126/science.1114016

Reports

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,3 Jane A. McKeating,1{dagger} Charles M. Rice1{ddagger}

Many aspects of the hepatitis C virus (HCV) life cycle have not been reproduced in cell culture, which has slowed research progress on this important human pathogen. Here, we describe a full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc). Replication of HCVcc was robust, producing nearly 105 infectious units per milliliter within 48 hours. Virus particles were filterable and neutralized with a monoclonal antibody against the viral glycoprotein E2. Viral entry was dependent on cellular expression of a putative HCV receptor, CD81. HCVcc replication was inhibited by interferon-{alpha} and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals.

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.

Published online 9 June 2005

Include this information when citing this paper.

* Present address: Alexion Antibody Technologies, San Diego, CA 92121, USA.

{dagger} Present address: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, UK.

{ddagger} To whom correspondence should be addressed. E-mail: ricec{at}rockefeller.edu

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