Orderly Steps in Progression of JC Virus to Virulence in the Brain.

Progressive multifocal leukoencephalopathy is a neurodegenerative disease caused by demyelination in the brain. The demyelination is due to infection of oligodendroglial cells by polyomavirus JC, a circular DNA virus. The virus resides as an archetype form in uroepithelial cells and bone marrow of more than 70% of adults, in whom it seldom causes overt symptoms. The JC viral form infecting the brain differs from the archetype. This viral form contains two deletions and a duplication in the non-coding control region that are thought to be derived from the archetype. These rearrangements are necessary for neurovirulence. This review considers how these rearrangements occur in the context of transit to the brain and adaptation to infect glial cells.