Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis

HepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatme...

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Veröffentlicht in:Journal of cellular physiology 2004-12, Vol.201 (3), p.447-458
Hauptverfasser: Sun, Bill S., Pan, Jingbo, Clayton, Marcy M., Liu, Jie, Yan, Xiaoping, Matskevich, Alexey A., Strayer, David S., Gerber, Michael, Feitelson, Mark A.
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container_end_page 458
container_issue 3
container_start_page 447
container_title Journal of cellular physiology
container_volume 201
creator Sun, Bill S.
Pan, Jingbo
Clayton, Marcy M.
Liu, Jie
Yan, Xiaoping
Matskevich, Alexey A.
Strayer, David S.
Gerber, Michael
Feitelson, Mark A.
description HepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatment. NS5B and HCV core protein were detectable. HCV stimulated HepG2 cell growth and survival in culture, in soft agar, and accelerated tumor growth in SCID mice. These mice became HCV RNA positive in blood, where the virus was also sensitive to IFNα. The RNA banded at the density of HCV, and was resistant to RNase prior to extraction. Hence, HCV stably replicates in HepG2 cells, stimulates hepatocellular growth and tumorigenesis, and is susceptible to IFNα both in vitro and in vivo. © 2004 Wiley‐Liss, Inc.
doi_str_mv 10.1002/jcp.20083
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Animals
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
Gene Expression Regulation, Viral
Hepacivirus - drug effects
Hepacivirus - genetics
Hepacivirus - physiology
Hepatocytes - metabolism
Hepatocytes - pathology
Hepatocytes - virology
Humans
Interferon-alpha - pharmacology
Mice
Mice, SCID
RNA Viruses - genetics
RNA Viruses - isolation & purification
Transfection
Viral Core Proteins - metabolism
Viral Nonstructural Proteins - metabolism
Virus Replication
title Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis
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