Human papovavirus BK early gene regulation in nonpermissive cells

Abstract

The human papovavirus BK latently infects a majority of the population worldwide, and its DNA has been found in human tumor tissue. BKV is known to be highly oncogenic in rodents, and is capable of transforming cells in vitro. Rearrangements in the transcriptional regulatory sequences controlling expression of the transforming early gene, T antigen, are known to affect both the tumorigenic and transforming properties of this virus. Little is known about the mechanism by which this occurs. We have examined several aspects of BKV early promoter/enhancer regulation in cell types which the virus transforms, baby hamster kidney (BHK) and newborn rat kidney (NRK) cells, and compare them to the same processes in monkey kidney CV1 cells. We find that BKV early transcriptional efficiency requires the same enhancer repeat elements in all three cell types, but that requirements for sequences to the early and late side of these repeats vary between these cells. While the BKV T antigen was found to repress early gene expression from the BKV early promoter in CV1 cells, this effect was lower in BHK cells and essentially absent in NRK cells. The impaired autoregulation observed in rodent cells may be the result of inefficient T antigen production in these cells. DNA replication from the BKV origin was not detected in either BHK or NRK cells. Finally, we find no correlation between the efficiency of the BKV early regulatory region in directing gene expression and the ability to transform NRK cells.