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Whole genome expression profiling of hepatitis B virus-transfected cell line reveals the potential targets of anti-HBV drugs

The Pharmacogenomics Journal volume 8, pages 61–70 (2008)Cite this article

Abstract

Hepatitis B virus (HBV) infection is a major health concern world wide, and few effective treatments have been developed. It has recently been reported that inhibiting host-cell proteins can prevent viral infection. The human genome may contain more genes required for HBV infection and replication than the viral genome. A systematic approach to find these potential antiviral targets is by host gene expression analysis using DNA microarrays. The aim of this study was to identify and validate novel cellular anti-HBV targets. The Human Whole Genome Bioarray was used to analyze differentially expressed genes in HepG2.2.15 cells and HepG2 cells. Altered gene expression in HepG2.2.15 cells was studied following treatment with the anti-HBV drug, lamivudine. Genes that were differentially expressed during HBV infection and reversed with anti-HBV drugs were validated by semiquantitative reverse transcription-PCR. Bioinformatics analysis revealed ABHD2, EREG, ACVR2B, CDC34, KHDRBS3 and RORA as potential cellular anti-HBV targets. Antisense oligodeoxynucleotides were used to test the antiviral activity of these potential targets. Results strongly suggested that inhibition of ABHD2 or EREG significantly blocked HBV propagation in HepG2.2.15 cells. This study demonstrates that ABHD2 and EREG are essential for HBV propagation and provides strong evidence that these proteins could be used as potential targets for anti-HBV drugs.

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Acknowledgements

This work is a Key Program supported by grant from the national nature science foundation of China (No. 30530650), a grant from National Science Fund for Distinguished Young Scholars (No. 30625041) and the special funds for major state basic research program of China (973 program) (NO. 2005CB522902). We acknowledge Yiwei Fan for synthesizing the ASODNs.

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Authors and Affiliations

  1. Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, P.R. China

    X R Ding, J Yang, D C Sun, S K Lou & S Q Wang

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Correspondence to S Q Wang.

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Ding, X., Yang, J., Sun, D. et al. Whole genome expression profiling of hepatitis B virus-transfected cell line reveals the potential targets of anti-HBV drugs. Pharmacogenomics J 8, 61–70 (2008). https://doi.org/10.1038/sj.tpj.6500459

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