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 (IFN alpha) 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 IFN alpha. 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 IFN alpha both in vitro and in vivo.
Sun
Bill S
BS
Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799, USA.
Pan
Jingbo
J
Clayton
Marcy M
MM
Liu
Jie
J
Yan
Xiaoping
X
Matskevich
Alexey A
AA
Strayer
David S
DS
Gerber
Michael
M
Feitelson
Mark A
MA
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D012328:RNA Viruses / Q000235:genetics / Q000302:isolation & purification; D014162:Transfection; D014758:Viral Core Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
D016898:Interferon-alpha; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase