The presence of VP1 mutations in BKPyV and JCPyV isolates from BKVN and PML patients, as well as rearranged NCCRs in JCPyV-PML, supports the idea that some level of mutagenesis of PyV genomic DNA is inherent in its replication process. The gene discussed is PML; the disease is progressive multifocal leukoencephalopathy.