Tissue specific phenotypes of polyomavirus A and B enhancer transpositions and duplications: positional and nonpositional effects on replication in lymphoid cells.

We have extended our studies using the mouse lymphoid cell system to determine if polyomavirus (Py) cell type specificity is a consequence of the simple presence of either the A and B enhancers, or if specificity results from specific combinations or arrangements of the individual enhancer elements. Mouse fibroblasts and several T lymphoid cell lines were transfected with wild-type DNA or genomes containing either a deletion of the B enhancer, a transposition of the A and B enhancers relative to their normal positions, or a tandem duplication of either the A or B enhancers. In some cells activation of DNA replication was dependent on the simple presence of the B enhancer and not upon its position, as all genomes containing a B enhancer replicated efficiently. In other cells, deletion or transposition of the B enhancer abolished DNA replication which suggested that activation depended upon the position of this element. The A enhancer core duplication replicated well in lymphoid cell lines, but duplication of the B enhancer did not yield a generally efficient configuration. We have interpreted these results to suggest that individual enhancer components can interact via specific combinational principles to yield cell type specific effects upon Py DNA replication.