title: Complete replication of hepatitis C virus in cell culture.
abstract: 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 10(5) 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.
authors.affiliation: Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Lindenbach
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Syder
authors.forename: Benno
authors.initials: B
authors.lastname: Wölk
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Tellinghuisen
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Liu
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002499:Centrifugation, Density Gradient; D017077:Culture Media, Conditioned; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D009154:Mutation; D009500:Neutralization Tests; D012367:RNA, Viral / Q000096:biosynthesis; D012093:Replicon; D012692:Serial Passage; D060225:Tetraspanin 28; D014162:Transfection; D014759:Viral Envelope Proteins / Q000032:analysis / Q000096:biosynthesis; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000096:biosynthesis; D014771:Virion / Q000502:physiology; D014776:Virus Cultivation; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; D000998:Antiviral Agents; D017077:Culture Media, Conditioned; D016898:Interferon-alpha; D012367:RNA, Viral; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C554798:CD81 protein, human; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase