The identification of hepatitis B virus X gene responsive elements reveals functional similarity of X and HTLV-I tax.

The human hepatitis B virus (HBV) X gene encodes a general transactivator which was suggested to be a potential factor in viral hepatocarcinogenesis. We show here that this protein transactivates the HBV enhancer linked either to the X gene promoter or heterologous promoters. Analysis of individual elements of the HBV enhancer revealed that the E element is sufficient to respond to X and is termed hence the X responsive element (XRE). Interestingly, XRE shares sequence similarity with the HTLV-I taxI responsive element (21 bp repeat or taxRE), and both elements bind similar nuclear proteins. The functional significance of this sequence similarity was demonstrated by the ability of XRE to respond to taxI. We also show that both X and taxI have the capacity to activate transcription through a second cis element, the NF-kappa B binding site. The response pattern of these viral regulators is also similar and both act in a concentration dependent manner. They are very active in low amounts, but almost inactive at high concentrations. Based on these observations, we suggest a common mechanism of action by regulator genes of distinct viruses.