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World J Gastroenterol. May 14, 2008; 14(18): 2877-2881
Published online May 14, 2008. doi: 10.3748/wjg.14.2877
Hepatitis C virus core proteins derived from different quasispecies of genotype 1b inhibit the growth of Chang liver cells
Xue-Bing Yan, Lei Mei, Xia Feng, Mei-Rong Wan, Zhi Chen, Nicole Pavio, Christian Brechot
Xue-Bing Yan, Lei Mei, Department of Infectious Diseases, the First Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China
Lei Mei, Changshu No. 2 People’s Hospital, 68 Haiyu South Road, Changshu 215500, Jiangsu Province, China
Xia Feng, Mei-Rong Wan, Department of Central Labatory, the First Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China
Zhi Chen, Institute of Infectious Diseases, the First Affiliated Hospital, College of Medical Science, Zhejiang University; Key Lab of Infectious Diseases, Ministry of Public Health, Hangzhou, 310003, Zhejiang Province, China
Nicole Pavio, Christian Brechot, Inserm, U785, Villejuif, F-94804, France; Universite Paris sud, Centre Hepato-Biliaire, Hopital Paul Brousse, Villejuif F-94804, France
Author contributions: Yan XB and Mei L contributed equally to this work; Yan XB, Mei L and Chen Z designed the research; Mei L, Feng X and Wan MR performed the experiments and Pavio N and Brechot C contributed the plasmids.
Correspondence to: Xue-Bing Yan, Department of Infectious Diseases, The First Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China. yxbxuzhou@126.com
Telephone: +86-516-85802180
Fax: +86-516-85802215
Received: December 22, 2007
Revised: February 4, 2008
Published online: May 14, 2008
Abstract

AIM: To investigate the influence of different quasispecies of hepatitis C virus (HCV) genotype 1b core protein on growth of Chang liver cells.

METHODS: Three eukaryotic expression plasmids (pEGFP-N1/core) that contained different quasispecies truncated core proteins of HCV genotype 1b were constructed. These were derived from tumor (T) and non-tumor (NT) tissues of a patient infected with HCV and C191 (HCV-J6). The core protein expression plasmids were transiently transfected into Chang liver cells. At different times, the cell cycle and apoptosis was assayed by flow cytometry, and cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT) assay.

RESULTS: The proportion of S-phase Chang liver cells transfected with pEGFP-N1/core was significantly lower than that of cells transfected with blank plasmid at three different times after transfection (all P < 0.05). The proliferation ratio of cells transfected with pEGFP-N1/core was significantly lower than that of cells transfected with blank plasmid. Among three different quasispecies, T, NT and C191 core expression cells, there was no significant difference in the proportion of S- and G0/G1-phase cells. The percentage of apoptotic cells was highest for T (T > NT > C191), and apoptosis was increased in cells transfected with pEGFP-N1/core as the transfection time increased (72 h > 48 h > 24 h).

CONCLUSION: These results suggest that HCV genotype 1b core protein induces apoptosis, and inhibits cell-cycle progression and proliferation of Chang liver cells. Different quasispecies core proteins of HCV genotype 1b might have some differences in the pathogenesis of HCV persistent infection and hepatocellular carcinoma.

Keywords: Hepatitis C virus, Core protein, Chang liver cells, Cell cycle, Apoptosis