JCV isolates from the brain or cerebrospinal fluid (CSF) of PML patients usually harbor unique NCCR mutations, deletions, and/or rearrangements, some of which have been shown to increase viral transcription in cultured cells of central nervous system origin; in addition, ~80–90% of PML JCV isolates carry VP1 point mutations [10–14], and mutations in agnoprotein have been identified in the PML-variant JCV encephalopathy [15]. This evidence concerns the gene PML and progressive multifocal leukoencephalopathy.