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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Antibodies, Monoclonal / immunology
-
Antibodies, Viral / immunology
-
Antigens, CD / metabolism
-
Antiviral Agents / pharmacology
-
Cell Line, Tumor
-
Centrifugation, Density Gradient
-
Culture Media, Conditioned
-
Genome, Viral
-
Hepacivirus / genetics
-
Hepacivirus / immunology
-
Hepacivirus / physiology*
-
Humans
-
Interferon-alpha / pharmacology
-
Mutation
-
Neutralization Tests
-
RNA, Viral / biosynthesis
-
Replicon
-
Serial Passage
-
Tetraspanin 28
-
Transfection
-
Viral Envelope Proteins / analysis
-
Viral Envelope Proteins / biosynthesis
-
Viral Nonstructural Proteins / analysis
-
Viral Nonstructural Proteins / biosynthesis
-
Virion / physiology
-
Virus Cultivation*
-
Virus Replication*
Substances
-
Antibodies, Monoclonal
-
Antibodies, Viral
-
Antigens, CD
-
Antiviral Agents
-
CD81 protein, human
-
Culture Media, Conditioned
-
Interferon-alpha
-
RNA, Viral
-
Tetraspanin 28
-
Viral Envelope Proteins
-
Viral Nonstructural Proteins
-
glycoprotein E2, Hepatitis C virus
-
NS-5 protein, hepatitis C virus