The hepatitis B virus pre-S/S(t) transactivator is generated by 3' truncations within a defined region of the S gene.
AUTOR(ES)
Lauer, U
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=289082Documentos Relacionados
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