[Frontiers in Bioscience 16, 2586-2597, June 1, 2011]

Genomic instability caused by hepatitis B virus: into the hepatoma inferno

Yi-Hsuan Hsieh1, Jye-Lin Hsu1, Ih-Jen Su2, Wenya Huang1,3,4

1Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, 2Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan, 3Institute of Basic Medicine, College of Medicine, National Cheng Kung University, 4Center for Signal Transduction and Gene Regulation, National Cheng Kung University, Tainan, Taiwan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Basis of genomic instability
4. Metabolism of genotoxins in liver
5. Genomic instability in liver carcinogenesis
6. Association of hepatitis B virus infection with host genome instability 6.1. Viral oncoprotein HBx induces cell cycle progression and inhibits DNA repair
6.2. The novel pre-S2 mutant LHBS induces endoplasmic reticulum stress-induced oxidative DNA damage and mutation
7. Conclusions
8. Acknowledgments
9. References

1. ABSTRACT

Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide, especially in Asia. HBV induces HCC through multiple oncogenic pathways. Hepatitis-induced hepatocyte inflammation and regeneration stimulates cell proliferation. The interplay between the viral and host factors activates oncogenic signaling pathways and triggers cell transformation. In this review, we summarize previous studies, which reported that HBV induces host genomic instability and that HBV-induced genomic instability is a significant factor that accelerates carcinogenesis. The various types of genomic changes in HBV-induced HCC-chromosomal instability, telomere attrition, and gene-level mutations-are reviewed. In addition, the two viral factors, HBx and the pre-S2 mutant large surface antigen, are discussed for their roles in promoting genomic instability as their main features as viral oncoproteins.