The small DNA tumor viruses like SV40, polyoma, BKV and JCV of the papovavirus family provide attractive model systems for the study of the host cell machinery involved in replication, gene expression and the oncogenic transformation of mammalian cells. Of these viruses, SV40 and polyoma (which grow in monkey and mouse cells, respectively) have been well studied, but very little is known about the biology of the human papovaviruses, BKV and JCV. About 75% of the human population worldwide is infected with BKV at an early age and the virus persists in a latent form through much of the lifetime of the infected person. Though the primary infection is believed to be innocuous, the virus is activated in immunosuppressed or immunocompromised patients, as judged by the appearance of virus in the urine. A comparison of sequences of SV40 and BKV shows that they are strikingly similar. Yet the two viruses have different host ranges and oncogenic potential and only a small amount of DNA sequence homology in their regulatory or control sequences. In this proposal, we are interested in the mechanisms of transformation by BKV. We plan to study the regulation of expression of the transforming protein, T antigen, as well as the mechanism by which T antigen transforms cells. The cis-acting DNA sequences in the BKV ori-promoter region and the trans-acting factors that modulate T antigen synthesis by binding to the cis-acting sequences will be investigated. We are also interested in the DNA sequences and proteins that determine host range and tissue tropism of the human polyomaviruses. Finally, we plan to study the wild-type and mutant forms of the BKV T antigen and the mechanisms by which T antigen might transform cells.
