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The genome of human hepatitis B virus (HBV) contains an enhancer element within a 360-base-pair transcribed region located between sequences encoding the virus surface and core antigens. Beyond the usual properties associated with enhancers (i.e., activity 5' or 3' of a heterologous promoter and relative orientation independence), DNA sequences encompassing this enhancer exhibited unexpected characteristics. Using gene expression assays in both stably and transiently transfected cells, we found that the HBV enhancer element, when located in a transcribed region of chimeric genes, dramatically increased expression levels of genes controlled by the simian virus 40 promoter/enhancer. This synergism was not observed, however, when the HBV enhancer was located outside of the transcribed region. When these transcribed sequences were reversed in orientation, expression levels decreased significantly. These data suggest that RNA stability and transcriptional activity may be affected by sequences associated with this DNA region. In contrast to the findings of others, we found that the HBV enhancer activated transcription in a relatively cell-type-independent manner when the enhancer was located either 5' of the promoter or in the 3' untranslated region of gene constructs. The implications of these and other properties of the HBV enhancer region on viral gene expression and its life cycle are discussed.

Properties of the human hepatitis B virus enhancer: position effects and cell-type nonspecificity