Polyomavirus infections of the CNS

Polyomaviridae are a family of small, circular DNA viruses with several highly prevalent human pathogens. In contrast, human CNS infections are uncommon, usually resulting from betapolyomavirus John Cunningham virus (JCV). The most frequent CNS infection is progressive multifocal leukoencephalopathy (PML), a primarily demyelinating disorder with exuberant viral replication in oligodendroglia. Other CNS involvement includes JCV-associated meningitis, cerebellar granule cell neuronopathy, and JCV encephalopathy, with clinical presentations reflecting anatomic and cellular viral tropisms. Less frequently, BK virus may cause meningoencephalitis. Host immune status is critical to disease pathogenesis because of these opportunistic infections activate with immunocompromise and immune dysregulation. Although PML is most often fatal, restoration of immunity may enable prolonged survival. However, counterintuitive manifestations can occur in PML-immune reconstitution inflammatory syndrome, where clinical deterioration occurs with enhanced immunity and deleterious brain inflammation. There are presently no antiviral therapies with proven efficacy for PML, and immunomodulatory therapeutic strategies are under investigation.