The hepatitis B virus pre-S/S(t) transactivator is generated by 3' truncations within a defined region of the S gene.
Recently, it was reported that 3' truncation of an integrated surface gene (pre-S2/S) cloned from a hepatitis B virus (HBV)-associated hepatoma gave rise to the generation of a C-terminally truncated middle surface protein (MHBst), which surprisingly exerted a transcriptional transactivator function. To define the molecular requirements for the generation of transactivating MHBs(t) proteins, a 3' deletion analysis of the HBV pre-S2/S gene was performed. In cotransfection experiments with reporter plasmid pSV2CAT, full-length pre-S2/S genes or pre-S2/S genes with minor 3'-terminal deletions did not exhibit transactivator activity. In contrast, deletion of C-terminal hydrophobic region III of the S domain generated the transactivator function. Further stepwise 3' deletions, removing hydrophobic region II and both hydrophilic regions of the S domain, did not interfere with the transactivator activity; it was completely abolished, however, after additional deletion of hydrophobic region I. The results of this study define a range within the S open reading frame (between HBV nucleotides 221 and 573), termed the trans-activity-on region, in which 3' deletions give rise to the generation of transactivating MHBs(t) proteins. Within this region, not only 3' deletions but also the introduction of a stop codon activated the transactivator function, indicating that point mutations of integrated HBV DNA also may give rise to the synthesis of transactivating MHBs(t) proteins in vivo.
Lauer
U
U
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Weiss
L
L
Hofschneider
P H
PH
Kekulé
A S
AS
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000382:microbiology; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000382:microbiology; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics*
D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D015534:Trans-Activators; D015678:Viral Structural Proteins; C050807:presurface protein 2, hepatitis B surface antigen