Major differences between WHV and HBV in the regulation of transcription.

Studies were carried out to further characterize enhancer and promoter elements on the woodchuck hepatitis virus (WHV) genome. We were able to confirm the existence of WHV promoters analogous to the major promoters of the related human hepatitis B virus (HBV) and of an enhancer analogous to the recently described WHV E2 element (Ueda, K., Wei, Y., and Ganem, D., Virology 217, 413, 1996). However, we were unable to identity an enhancer analogous to the E1 element of (HBV), despite the fact that these two viruses share a high degree of sequence homology and genetic organization. Some factor binding sites in the E1 region appeared to be conserved between the two viruses and may be required for the activity of the overlapping X gene promoter of WHV. Others did not appear to be essential for WHV X gene promoter activity, and their functional activity, if any, was not revealed. Our failure to detect a functional enhancer element in the region of WHV homologous to the HBV E1 enhancer may indicate that (i) fundamental differences exist in transcriptional regulation of the small circular genomes of WHV and HBV; (ii) WHV contains an E1 element which is functional in the context of the intact viral genome, but which is unable to function in the context of the various expression constructs used in our experiments; or (iii) correct regulation of WHV transcription via an E1 element is dependent upon transcription factors which are not expressed in the liver-specific cell lines used in our experiments.