Adeno-associated virus Rep78 binds to E2-responsive element 1 of bovine papillomavirus type 1

Adeno-associated virus type-2 (AAV-2) is a helper-dependent parvovirus that has been implicated in the inhibition of replication and oncogenic transfo rmation of bovine papillomavirus type-1 (BPV-I) and other transforming DNA viruses. Previous studies have suggested that the Rep78 protein of AAV-2 is a key player mediating this effect. In this report we have analyzed the ef fect of AAV-2 Rep78 protein on the regulation of gene expression of a repor ter gene under the control of the long control region (LCR) of BPV-1. Our r esults show that Rep78 is capable of down-regulating the promoter activity of the the LCR in vivo in tissue culture cells. Inhibition of LCR activity in vivo suggested the need for Rep78 to bind to a region of the LCR promote r spanning the E2-responsive elements of BPV-1, This observation was furthe r confirmed in vitro with gel shift assays showing specific binding of Rep7 8 to DNA oligonucleotides containing E2-responsive element 1 (E2RE(1)) sequ ences of BPV-1 LCR. Our results expand the understanding of the mechanism o f trans-regulation mediated by Rep78 and involving this protein and DNA seq uences with complex secondary structure.