WOODCHUCK HEPATITIS-VIRUS CONTAINS A TRIPARTITE POSTTRANSCRIPTIONAL REGULATORY ELEMENT

The hepatitis B virus posttranscriptional regulatory element (HBVPRE) is a cis-acting RNA element that partially overlaps with enhancer I an d is required for the cytoplasmic accumulation of HBV surface RNAs. We find that the closely related woodchuck hepatitis virus (WHV), which has been shown to lack a functional enhancer I, also contains a posttr anscriptional regulatory element (WPRE). Deletion analysis suggests th at the WPRE consists of three independent subelements. Comparison of t he bipartite HBVPRE and tripartite WPRE activities reveals that the tr ipartite WPRE is two to three times more active than the bipartite HBV PRE. Mutation of a single WPRE subelement decreases WPRE activity to t he level of the HBVPRE. Bipartite and tripartite chimeras of the WPRE and HBVPRE possess activities which suggest that elements containing t hree subelements are posttranscriptionally stronger than those contain ing two. These data demonstrate that the posttranscriptional regulator y element is conserved within the mammalian hepadnaviruses and that it s strength is determined by the number of subelements within the RNA.