Complete replication of hepatitis C virus in cell culture.
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.
Lindenbach
Brett D
BD
Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Evans
Matthew J
MJ
Syder
Andrew J
AJ
Wölk
Benno
B
Tellinghuisen
Timothy L
TL
Liu
Christopher C
CC
Maruyama
Toshiaki
T
Hynes
Richard O
RO
Burton
Dennis R
DR
McKeating
Jane A
JA
Rice
Charles M
CM
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
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