HEPATITIS-B VIRUS TRANSACTIVATOR PROTEIN, HBX, ASSOCIATES WITH THE COMPONENTS OF TFIIH AND STIMULATES THE DNA HELICASE ACTIVITY OF TFIIH

Human hepatitis B virus genome encodes a protein, termed HBx, that is widely recognized as a transcriptional transactivator. While HBx does not directly bind cis-acting transcriptional control elements, it has been shown to associate with cellular proteins that bind DNA. Because HBx transactivated a large number of viral/cellular transcriptional co ntrol elements, we looked for its targets within the components of the basal transcriptional machinery. This search led to the identificatio n of its interactions with TFIIH. Here, we show that HBx interacts wit h yeast and mammalian TFIIH complexes both in vitro and in vivo. These interactions between HBx and the components of TFIIH are supported by several lines of evidence including results from immunoprocedures and direct methods of measuring interactions. We have identified ERCC3 an d ERCC2 DNA helicase subunits of holoenzyme TFIIH as targets of HBx in teractions. Furthermore, the DNA helicase activity of purified TFIIH f rom rat liver and, individually, the ERCC2 component of TFIIH is stimu lated in the presence of HBx. These observations suggest a role for HB x in transcription and DNA repair.