The X-gene of human hepatitis B virus transactivates the c-jun and alpha-fetoprotein genes.

The X-gene product of human hepatitis B virus is a transacting transcriptional factor which activates a variety of heterologous viral and host promoters/enhancers. We have found that the X-gene product can significantly transactivate the regulatory sequences located at the 5'-upstream of the c-jun oncogene when a reporter plasmid containing the sequences was co-transfected to HepG2 cells with an X-gene expression plasmid. The results of mutational analysis indicate that the X-gene activation requires the AP-1 sequence of the c-jun gene. Furthermore, we also found that the X-gene is capable of activating the 5'-upstream sequence of the alpha-fetoprotein gene. There are at least two elements that respond to the X-gene transactivation. One is located in the sequences between -5,100 and -2,900, and the other is at the C/EBP site. Therefore, the X-gene activates the c-jun and alpha-fetoprotein genes through different host factors, namely AP-1 and C/EBP, respectively. The results of c-jun activation by the X-gene strongly support the previous hypothesis that the X-gene may play a critical role in the development of hepatocellular carcinoma.