REGULATION OF THE HUMAN BETA-INTERFERON GENE EXPRESSION BY HEPATITIS-B VIRUS

Individuals chronically infected with hepatitis B virus (HBV) have a deficiency in the in vivo interferon response. To determine whether HBV suppresses the synthesis of human beta-interferon, a series of recombinant bovine papilloma virus (BPV) plasmids that contained the human beta-interferon gene and various fragments of HBV DNA were constructed. Mouse C127 fibroblast cells were transfected with various recombinant BPV plasmids and permanently transformed cell lines were established by geneticin sulfate G418 selection.;A hybrid gene in which the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene is under the control of the regulatory region of the human beta-interferon gene was constructed. The expression of the CAT gene was inhibited not only by the entire HBV genome but also by the 1828 bp BamHI HBV DNA fragment. A frameshift mutation introduced within the structural gene of the core antigen abolishes the inhibitory activity. These results suggest that HBV suppresses the expression of the human beta-interferon by interacting in the same manner with the ;In addition, the 2755 bp BglII HBV DNA fragment containing the surface antigen gene and the ORF X was identified to have a transactivating activity in a transient DNA expression system. The transactivating activity was defined and attributed to the HBV X antigen gene. These results strongly suggest that transcription of the HBV X antigen gene is necessary for transactivation. (Abstract shortened with permission of author.).;To determine the stage of the synthesis of human beta-interferon that is inhibited by the product of the 1828 bp BamHI HBV DNA fragment, levels of human beta-interferon-specific RNA in the various transformed cell lines were measured. The level of RNA specific for human beta-interferon gene was decreased in only those transformed C127 cells that contained the 1828 bp BamHI HBV DNA fragment. Results of nuclear run-on experiments to detect the rate of transcription of the human beta-interferon gene indicate that the suppression of interferon synthesis by HBV occurs at the level of transcription.