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J Virol, April 1998, p. 3060-3065, Vol. 72, No. 4
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

Jun Chang,1 Se-Hwan Yang,1 Young-Gyu Cho,1 Soon Bong Hwang,2 Young Shin Hahn,3 and Young Chul Sung1,*

Department of Life Science, Center for Biofunctional Molecules, School of Environmental Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk,1 and Institute of Environment and Life Science, Hallym Academy of Sciences, Hallym University, Chuncheon,2 Republic of Korea, and Beirne Carter Center for Immunology Research, Health Sciences Center, University of Virginia, Charlottesville, Virginia3

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.

* 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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