Publisher Summary The clinical and histopathological characteristics of polyomaviruses (PML) have been known for many years, the pathogenesis of the disease is largely unknown and has recently been intensively studied. Elucidating the effects of cell type-restricted and temporarily repressed gene expression is essential for an understanding of the pathogenesis of the polyomaviruses. The complex structure of the DNA sequences responsible for transcriptional regulation, and the numerous proteins characterized so far clearly point to the transcriptional control region as the regulatory element that can be targeted by intracellular and extracellular signals, allowing differential responses to host related immunological impairment. The characterization of enhancing factors provided directly or indirectly by changes in the immunological control of infection will therefore increase understanding of the processes leading to severe cytolysis in PML and may also offer prospects for future treatment.