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 promo ters of the related human hepatitis a virus (HBV) and of an enhancer a nalogous to the recently described WHV E2 element (Ueda, K, Wei, Y., a nd Ganem, D., Virology 217, 413, 1996). However, we were unable to ide ntify an enhancer analogous to the El element of (HBV), despite the fa ct that these two viruses share a high degree of sequence homology and genetic organization. Some factor binding sites in the El region appe ared to be conserved between the two viruses and may be required for t he activity of the overlapping X gene promoter of WHV. Others did not appear to be essential for WHV X gene promoter activity, and their fun ctional activity, if any, was not revealed. Our failure to detect a fu nctional enhancer element in the region of WHV homologous to the HBV E l enhancer may indicate that (i) fundamental differences exist in tran scriptional regulation of the small circular genomes of WHV and HBV; ( ii) WHV contains an Fl element which is functional in the context of t he 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 El element is depende nt upon transcription factors which are not expressed in the liver-spe cific cell lines used in our experiments. (C) 1997 Academic Press.