Key role of a CCAAT element in regulating hepatitis B virus surface protein expression.
Two separate promoters, the upstream preS1 and the downstream S promoters, give rise to transcripts encoding three forms of the hepatitis B virus surface protein. Overproduction of large surface protein because of increased preS1 transcripts leads to a block in secretion of all forms of the surface protein and of virion particles. We show here that a CCAAT element in the S promoter not only increases the amount of S transcripts, but also decreases the amount of preS1 transcripts by up to fivefold. Consequently, mutations in this element cause intracellular accumulation of surface proteins because of the secretory block. Therefore, this CCAAT element appears to be critical for maintaining the high ratio of S versus preS1 transcripts that is necessary for the viral life cycle.
Department of Pathology, University of California, San Francisco 94143.
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D001483:Base Sequence; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000096:biosynthesis*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014771:Virion / Q000378:metabolism
D017931:DNA Primers; D006514:Hepatitis B Surface Antigens