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PMID: 15951748 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Production of infectious hepatitis C virus in tissue culture from a cloned viral genome.

Nature medicine ·Vol. 11 ·No. 7 ·2005-07-00 ·Pages 791-6

Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Kräusslich HG, Mizokami M, Bartenschlager R, Liang TJ

Abstract

Hepatitis C virus (HCV) infection causes chronic liver diseases and is a global public health problem. Detailed analyses of HCV have been hampered by the lack of viral culture systems. Subgenomic replicons of the JFH1 genotype 2a strain cloned from an individual with fulminant hepatitis replicate efficiently in cell culture. Here we show that the JFH1 genome replicates efficiently and supports secretion of viral particles after transfection into a human hepatoma cell line (Huh7). Particles have a density of about 1.15-1.17 g/ml and a spherical morphology with an average diameter of about 55 nm. Secreted virus is infectious for Huh7 cells and infectivity can be neutralized by CD81-specific antibodies and by immunoglobulins from chronically infected individuals. The cell culture-generated HCV is infectious for chimpanzee. This system provides a powerful tool for studying the viral life cycle and developing antiviral strategies.

MeSH Terms
Animals Antibodies/pharmacology Antigens, CD/immunology Biophysical Phenomena Biophysics Carcinoma, Hepatocellular/virology Cell Line, Tumor Cloning, Molecular Genome, Viral Hepacivirus/growth & development,isolation & purification,pathogenicity Hepatitis C/drug therapy,immunology Humans Immune Sera Liver Neoplasms/virology Microscopy, Electron Pan troglodytes RNA, Viral Tetraspanin 28 Transfection Virus Cultivation/methods
Chemicals
Antibodies Antigens, CD CD81 protein, human Immune Sera RNA, Viral Tetraspanin 28
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Wakita Takaji
Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan. wakita@tmin.ac.jp
Pietschmann Thomas
Kato Takanobu
Date Tomoko
Miyamoto Michiko
Zhao Zijiang
Murthy Krishna
Habermann Anja
Kräusslich Hans-Georg
Mizokami Masashi
Bartenschlager Ralf
Liang T Jake
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1078-8956
DOI
10.1038/nm1268
Email
wakita@tmin.ac.jp
Published
2005-07-00
Epub
2005-00-12
Pages
791-6
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC2918402
Subset
IM
Grants
NHLBI NIH HHS · N01HB27091 · United States
Intramural NIH HHS · Z01 DK054504-11 · United States
Intramural NIH HHS · Z99 DK999999 · United States
NHLBI NIH HHS · N01-HB-27091 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1038/nm1268 PMC Full Text View journal details
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