Hepatitis B virus surface (S) transactivator with DNA-binding properties

Chronic infection with hepatitis B virus (HBV) in humans is strongly linked to the development of hepatocellular carcinoma (HCC). Activation of growth -regulatory genes may play a crucial role in carcinogenesis. Proto-oncogene expression has been shown to be higher in HCC tissue with integrated HBV D NA than in the normal liver. Earlier, we showed that the 3' end of the HBV major surface gene (S) (426-855 nucleotides of the S region) is a transacti vator of the X promoter-enhancer regulatory element in co-transfection expe riments. This region expresses a truncated carboxy terminal S protein exten ding from amino acid residues 102 to 226. In this study, the truncated S pr otein (trc-S) was examined for its enhancing activity on several viral and cellular regulatory elements. The results indicate that trc-S activates rou s sarcoma virus long terminal repeat (LTR), human T-lymphotropic virus 2 LT R, human immunodeficiency virus 1 LTR, and the c-jun and c-fos promoters. E lectrophoretic mobility shift assays carried out to investigate its DNA-bin ding properties established that trc-S binds to HBV X promoter and oligonuc leotides representing binding sites for the AP1 and TFIID transcription fac tors. The specificity of this interaction was confirmed by using competitio n experiments and supershift assays. These experiments suggest that trc-S i s a transactivator of several,cellular and viral promoters and that this ac tivity is mediated by direct interaction with DNA. J. Med. Virol. 61:1-10, 2000. (C) 2000 Wiley-Liss, Inc.