THE X-GENE OF THE HEPATITIS-B VIRUS - TRANSACTIVATOR AND POTENTIAL ONCOGENE

Hepatitis B virus (HBV) contains an open reading frame (ORF) called X which can encode a 17 kDa polypeptide of 154 amino-acids. This protein is antigenic in man and represents a new serological marker of the HBV infection. The X-ORF encodes a transcriptional activator capable of stimulating the expression of genes under the control of the HBV enhancer as well as several RNA polymerase II and III promoters. This protein has an intrinsic serine/threonine protein-kinase activity which could be related to its transactivation function. The X protein does not bind directly to DNA but functions very likely by interacting with - or modifying - multiple cellular factors involved in transcription regulation. Stably transfected clones display malignant growth characteristics. Transgenic mice expressing the X gene product alone develop hepatocellular carcinomas. These data taken altogether suggest that the HBV-X protein, by its transactivating activity, plays a central role in viral hepatocarcinogenesis.