Complete Replication of Hepatitis C Virus in Cell Culture

• Published in: Science (American Association for the Advancement of Science) Vol. 309; no. 5734; pp. 623 - 626
• Main Authors: Lindenbach, Brett D., Evans, Matthew J., Syder, Andrew J., Wölk, Benno, Tellinghuisen, Timothy L., Liu, Christopher C., Maruyama, Toshiaki, Hynes, Richard O., Burton, Dennis R., McKeating, Jane A., Rice, Charles M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 22.07.2005; The American Association for the Advancement of Science
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Viral - immunology; Antigens, CD - metabolism; Antiviral Agents - pharmacology; Biological and medical sciences; Buoyancy; Cell culture; Cell culture techniques; Cell Line, Tumor; Cell lines; Centrifugation, Density Gradient; Culture Media, Conditioned; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genome, Viral; Genomes; Genotypes; Hep G2 cells; Hepacivirus - genetics; Hepacivirus - immunology; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C virus; Humans; Infections; Infectious diseases; Interferon-alpha - pharmacology; Kinetics; Microbiology; Mutation; Neutralization Tests; Pathogens; Properties; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Replicon; RNA; RNA, Viral - biosynthesis; Serial Passage; Tetraspanin 28; Transcripts (Written Records); Transfection; Viral Envelope Proteins - analysis; Viral Envelope Proteins - biosynthesis; Viral Nonstructural Proteins - analysis; Viral Nonstructural Proteins - biosynthesis; Virion - physiology; Virions; Virology; Virus Cultivation; Virus Replication; Viruses; Virus; RNA; Replication; Flaviviridae; Hepatitis C virus; Hepacivirus; In vitro
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1114016

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 105infectious 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-α and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals.