Use of a stable bovine papillomavirus vector to study inducible genes.

The human beta interferon (hIFN beta 1) gene has been cloned into a bovine papillomavirus type 1 (BPV-1)/pML2 vector. The recombinant DNAs can be maintained as stable plasmids in mouse cells, with no detectable rearrangements. The linked hIFN beta 1 gene is inducible with little line-to-line variability in independently transformed cell lines. The hIFN beta 1 gene is equally induced when it is inserted adjacent to or away from the BPV-1 enhancer. The great stability of the BPV-1/pML2 vector has allowed us to study the regulation of the hIFN beta 1 gene in mouse cells, with the construction of deleted and hybrid hIFN beta 1 genes. Using this strategy, we have confirmed that the 5' sequences of the hIFN beta 1 gene are involved in the induction mechanism. The entire hIFN beta 1 regulatory element is able to express heterologous genes with no induction, suggesting that the negative regulatory sequences present in the 3' region of the hIFN beta 1 regulatory element are not fully active on heterologous genes.