Abstract
Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma (HCC), but the molecular mechanisms underlying virally-induced tumorigenesis remain largely debated. In the absence of a dominant oncogene encoded by the HBV genome, indirect roles have been proposed, including insertional activation of cellular oncogenes by HBV DNA integration, induction of genetic instability by viral integration or by the regulatory protein HBx, and long term effects of viral proteins in enhancing immune-mediated liver disease. In this chapter, we discuss different models of HBV-mediated liver cell transformation based on animal systems of hepadnavirus infection as well as functional studies in hepatocyte and hepatoma cell lines. These studies might help identifying the cellular effectors connecting HBV infection and liver cell transformation.
Highlights
A number of viruses including the hepatitis B virus (HBV) have been recognized as human oncogenic agents [1,2]
The criteria accepted as establishing causality are based on (i) strong epidemiological association; (ii) finding of integrated or episomal viral genomes and gene products in Viruses 2009, 1 the tumor cells, and (iii) directly oncogenic properties revealed by cell transformation in culture and production of tumors in experimental animals
The long latency of hepatocellular carcinoma (HCC) development after the primary HBV infection may be interpreted as a sign of an indirect action of the virus
Summary
A number of viruses including the hepatitis B virus (HBV) have been recognized as human oncogenic agents [1,2]. The criteria accepted as establishing causality are based on (i) strong epidemiological association; (ii) finding of integrated or episomal viral genomes and gene products in Viruses 2009, 1 the tumor cells, and (iii) directly oncogenic properties revealed by cell transformation in culture and production of tumors in experimental animals. Concerning the second criteria, integrated HBV DNA sequences and episomal HBV genomes have been found in a majority of HBV-related tumors [7,8]. The hypothesis of a direct role of the virus is supported by the ability of HBV DNA to integrate into the genome of infected cells. We summarize some of the findings that support these notions and discuss the possible implications for our understanding of HBV-related tumorigenesis
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