The human JC polyomavirus (JCPyV): virological background and clinical implications

APMIS. 2013 Aug;121(8):685-727. doi: 10.1111/apm.12128. Epub 2013 Jun 19.


JC polyomavirus (JCPyV) was the first of now 12 PyVs detected in humans, when in 1964, PyV particles were revealed by electron microscopy in progressive multifocal leukoencephalopathy (PML) tissues. JCPyV infection is common in 35-70% of the general population, and the virus thereafter persists in the renourinary tract. One third of healthy adults asymptomatically shed JCPyV at approximately 50,000 copies/mL urine. PML is rare having an incidence of <0.3 per 100,000 person years in the general population. This increased to 2.4 per 1000 person years in HIV-AIDS patients without combination antiretroviral therapy (cART). Recently, PML emerged in multiple sclerosis patients treated with natalizumab to 2.13 cases per 1000 patients. Natalizumab blocks α4-integrin-dependent lymphocyte homing to the brain suggesting that not the overall cellular immunodeficiency but local failure of brain immune surveillance is a pivotal factor for PML. Recovering JCPyV-specific immune control, e.g., by starting cART or discontinuing natalizumab, significantly improves PML survival, but is challenged by the immune reconstitution inflammatory syndrome. Important steps of PML pathogenesis are undefined, and antiviral therapies are lacking. New clues might come from molecular and functional profiling of JCPyV and PML pathology and comparison with other replicative pathologies such as granule cell neuronopathy and (meningo-)encephalitis, and non-replicative JCPyV pathology possibly contributing to some malignancies. Given the increasing number of immunologically vulnerable patients, a critical reappraisal of JCPyV infection, replication and disease seems warranted.

Keywords: AIDS; HIV; JC virus; natalizumab; polyoma; progressive multifocal leukoencephalopathy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Brain / pathology
  • Brain / virology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / pathology
  • Immune Reconstitution Inflammatory Syndrome / virology
  • Integrin alpha4 / metabolism
  • JC Virus / classification
  • JC Virus / immunology
  • JC Virus / isolation & purification
  • JC Virus / physiology*
  • Leukoencephalopathy, Progressive Multifocal / drug therapy*
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / virology
  • Natalizumab
  • Phenotype
  • Virus Replication


  • Antibodies, Monoclonal, Humanized
  • Natalizumab
  • Integrin alpha4