Viral Hepatitis
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2004; 10(12): 1740-1745
Published online Jun 15, 2004. doi: 10.3748/wjg.v10.i12.1740
Gene expression profiles in an hepatitis B virus transfected hepatoblastoma cell line and differentially regulated gene expression by interferon-α
Xun Wang, Zheng-Hong Yuan, Ling-Jie Zheng, Feng Yu, Wei Xiong, Jiang-Xia Liu, Gen-Xi Hu, Yao Li
Xun Wang, Zheng-Hong Yuan, Ling-Jie Zheng, Wei Xiong, Jiang-Xia Liu, Department of Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Feng Yu, Gen-Xi Hu, Institute of Biochemistry and Cell Biology, CAS, Shanghai 200031, China
Yao Li, State Key Laboratory of Genetics, Fudan University School of Life Science, Shanghai 200433, China
Author contributions: All authors contributed equally to the work.
Supported by the Chinese State Basic Science Foundation, No. 1999054105 and Med-X Foundation of Fudan University
Correspondence to: Zheng-Hong Yuan, Department of Molecular Virology, Shanghai Medical College, Fudan University Fudan, 138 Yi Xue Yuan Road, Shanghai 200032, China. zhyuan@shmu.edu.cn
Telephone: +86-21-64161928 Fax: +86-21-64227201
Received: October 15, 2003
Revised: December 15, 2003
Accepted: December 22, 2003
Published online: June 15, 2004
Abstract

AIM: To study interactions between hepatitis B virus (HBV) and interferon-α in liver-derived cells.

METHODS: mRNAs were separately isolated from an HBV-transfected cell line (HepG22.2.15) and its parental cell line (HepG2) pre- and post-interferon-α (IFN-α) treatment at 6, 24 and 48 h, followed by hybridization with a cDNA microarray filter dotted with 14 000 human genes. After hybridization and scanning of the arrays, the data were analyzed using ArrayGauge software. The microarray data were further verified by Northern blot analysis.

RESULTS: Compared to HepG2 cells, 14 genes with known functions were down-regulated 3 to 12-magnitudes, while 7 genes were up-regulated 3-13 magnitudes in HepG22.2.15 cells prior to IFN-α treatment. After interferon-α treatment, the expression of four genes (vascular endothelial growth factor, tyrosine phosphate 1E, serine protein with IGF-binding motif and one gene of clathrin light chain) in HepG22.2.15 were up-regulated, while one gene encoding a GTP-binding protein, two genes of interferon-induced kinases and two proto-oncogenes were further down-regulated. Interestingly, under IFN-α treatment, a number of differentially regulated genes were new ESTs or genes with unknown functions.

CONCLUSION: The up-regulated genes in HepG22.2.15 cell line suggested that under IFN-α treatment, these repressed cellular genes in HBV infected hepatocytes could be partially restored, while the down-regulated genes were most likely the cellular genes which could not be restored under interferon treatment. These down-regulated genes identified by microarray analysis could serve as new targets for anti-HBV drug development or for novel therapies.

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