"Human polyomavirus 2" found in the central nervous system of PML patients almost invariably have differences in promoter sequence to "Human polyomavirus 2" found in healthy individuals. It is thought that these differences in promoter sequence contribute to the fitness of the virus in the CNS and thus to the development of PML. Certain transcription factors present in the early promoter sequences of "Human polyomavirus 2" can induce tropism and viral proliferation that leads to PML. The Spi-B factor was shown to be crucial in initiating viral replication in certain strains of transgenic mice. The protein encoded by these early sequences, T-antigen, also plays a key role in viral proliferation, directing the initiation of DNA replication for the virus as well as performing a transcriptional switch to allow for the formation of the various capsid and regulatory proteins needed for viral fitness. Further research is needed to determine the exact etiological role of T-antigen, but there seems to be a connection to the early initiation of the active virus from its archetypal dormant state.