John Cunningham virus
Citation, DOI & article data
John Cunningham virus (or human polyomavirus 2), universally known as the JC virus, is a ubiquitous double-stranded DNA virus of the polyomaviridae family 1. In immunocompromised individuals, reactivation can lead to a variety of disease of the central nervous system, the most common of which is progressive multifocal leukoencephalopathy (PML).
It has been reported that ~70% of adults have been exposed to this virus; however, no significant clinical syndrome has been associated with this acquisition in the majority of immunocompetent hosts 1.
Numerous causes of immunosuppression have been implicated in reactivation of the virus, including HIV/AIDS, malignancy (e.g. lymphoma), immonusuppressants, and immunomodulators (e.g. natalizumab for multiple sclerosis).
Infection with JC virus, usually asymptomatic, results in latent infection in various organs and tissues of the body. When patients are immunocompromised, the virus can reactivate and migrate to the central nervous system, with a predilection for glial cells, thus resulting in the classical leukoencephalopathy of progressive multifocal leukoencephalopathy (PML) 6.
Occasionally, mutations of the virus result in other cell types being targeted, with resultant distinct clinical manifestations, including 4-6:
- progressive multifocal leukoencephalopathy (PML)
- most common
- infection of glial cells
JC virus granule cell neuronopathy
- infection of the cerebellar granular cells
JC virus encephalopathy
- infection of cortical pyramidal neurons
JC virus meningitis
- infection of the meninges and choroid plexus
History and etymology
The virus was first described by Åström et al. in 1958 2, and was first isolated in 1971 by Padgett et al. The latter group assigned the name of the patient to the virus 3.
- 1. Bellizzi A, Anzivino E, Rodio DM et-al. New insights on human polyomavirus JC and pathogenesis of progressive multifocal leukoencephalopathy. Clin. Dev. Immunol. 2013;2013: 839719. doi:10.1155/2013/839719 - Free text at pubmed - Pubmed citation
- 2. Åström KE, Mancall EL, Richardson EP. Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease. Brain. 2000;81 (1): 93-111. Pubmed citation
- 3. Padgett BL, Walker DL, ZuRhein GM et-al. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971;1 (7712): 1257-60. Pubmed citation
- 4. Bag AK, Curé JK, Chapman PR, Roberson GH, Shah R. JC virus infection of the brain. (2010) AJNR. American journal of neuroradiology. 31 (9): 1564-76. doi:10.3174/ajnr.A2035 - Pubmed
- 5. Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. (2010) The Lancet. Neurology. 9 (4): 425-37. doi:10.1016/S1474-4422(10)70040-5 - Pubmed
- 6. Dang L, Dang X, Koralnik IJ, Todd PK. JC polyomavirus granule cell neuronopathy in a patient treated with rituximab. (2014) JAMA neurology. 71 (4): 487-9. doi:10.1001/jamaneurol.2013.4668 - Pubmed