Transactivation by Hepatitis B Virus May Contribute to Hepatocarcinogenesis

Abstract

Hepatitis B virus (HBV) is a major factor in the development of primary liver cancer in many areas of the world (Beasley 1982). The mechanisms by which HBV causes cell transformation are not understood (see Schlicht and Schaller, this volume). Viral DNA is integrated into hepatocyte chromosomes early after infection, but the cellular sites of integration are varied, and no common sites have been observed in tumors thus far (Koshy 1987). Furthermore, there is no evidence of integration at a genetic locus known to be concerned with transformation or cell proliferation. A single exception to this is a recently reported case in which HBV DNA was inserted into host DNA sequences homologous to the cellular v-erb-A protooncogene and certain steroid hormone receptors (Dejean et al. 1986; deThe et al. 1987) and which has since been shown to encode a novel retinoic acid receptor (Brand et al. 1988; Benbrook et al. 1988). It is also known that the integration of HBV DNA promotes genetic instability by chromosome rearrangements including deletion of cellular DNA and translocations (Koch et al. 1984; Rogler et al. 1987). The significance of these findings is at present unclear. Thus, as a rule, there is little evidence to provide a basis for a common cis-acting virus function in tumorigenesis.