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J Virol, April 1998, p. 3060-3065, Vol. 72, No. 4
Department of Life Science,
Received 20 August 1997/Accepted 11 December 1997
Persistent infection with hepatitis C virus (HCV) is associated
with the development of liver cirrhosis and hepatocellular carcinoma.
To examine the oncogenic potential of the HCV core gene product,
primary rat embryo fibroblasts (REFs) were transfected with the core
gene in the presence or absence of the H-ras oncogene. In
contrast to a previous report (R. B. Ray, L. M. Lagging, K. Meyer, and R. Ray, J. Virol. 70:4438-4443, 1996), HCV core
proteins from two different genotypes (type 1a and type 1b) were not
found to transform REFs to tumorigenic phenotype in cooperation with the H-ras oncogene, although the core protein was
successfully expressed 20 days after transfection. In addition, REFs
transfected with E1A- but not core-expressing plasmid showed the
phenotype of immortalized cells when selected with G418. The biological activity was confirmed by observing the transcription activation from
two viral promoters, Rous sarcoma virus long terminal repeat and simian
virus 40 promoter, which are known to be activated by the core protein
from HCV-1 isolate. In contrast to the result with primary cells, the
Rat-1 cell line, stably expressing HCV core protein, exhibited focus
formation, anchorage-independent growth, and tumor formation in nude
mice. HCV core protein was able to induce the transformation of Rat-1
cells with various efficiencies depending on the expression level of
the core protein. These results indicate that HCV core protein has an
oncogenic potential to transform the Rat-1 cell line but is not
sufficient to either immortalize primary REFs by itself or transform
primary cells in conjunction with the H-ras oncogene.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Hepatitis C Virus Core from Two Different Genotypes Has an
Oncogenic Potential but Is Not Sufficient for Transforming Primary
Rat Embryo Fibroblasts in Cooperation with the
H-ras Oncogene
*
Corresponding author. Mailing address: Department of
Life Science, Pohang University of Science and Technology, Pohang,
Kyungbuk 790-784, Republic of Korea. Phone: 82-562-279-2294. Fax:
82-562-279-5544. E-mail: ycsung{at}postech.ac.kr.
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