JC virus

The JC virus or John Cunningham virus (JCV) is a type of human polyomavirus (formerly known as papovavirus) and is genetically similar to BK virus and SV40. It was discovered in 1971 and named after the two initials of a patient with progressive multifocal leukoencephalopathy (PML). The virus causes PML and other diseases only in cases of immunodeficiency, as in AIDS, or immunosuppression, as in organ transplant patients.

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Epidemiology

The virus is very common in the general population, infecting 70 to 90 percent of humans; most people acquire JCV in childhood or adolescence ^[1]. It is found in high concentrations in urban sewage worldwide, leading some researchers to suspect contaminated water as a typical route of infection ^[2].

Minor genetic variations are found consistently in different geographic areas; thus, genetic analysis of JC virus samples has been useful in tracing the history of human migration ^[3].

Infection and pathogenesis

The initial site of infection may be the tonsils ^[4], or possibly the gastrointestinal tract ^[2]. The virus then remains latent in the gastrointestinal tract ^[5] and can also infect epithelial cells in the kidneys, where it continues to reproduce, shedding virus particles in the urine.

JCV can cross the blood-brain barrier into the central nervous system, where it infects oligodendrocytes and astrocytes, possibly through the 5-HT_2A serotonin receptor ^[6]. It is found within the brain even in people with no symptoms ^[7].

When immunodeficiency or immunosuppression allows JCV to reactivate, it attacks the previously infected tissues. In the kidneys, this results in hemorrhagic cystitis and ureteral stenosis; in the brain, it causes the usually fatal progressive multifocal leukoencephalopathy or PML by destroying oligodendrocytes. Several studies since 2000 have suggested that the virus is also linked to colorectal cancer, as JCV has been found in malignant colon tumors, but these findings are still controversial ^[8].

References

1. ^ Padgett, B.L. and Walker, D.L. (1973). "Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy". J. Infect. Dis. 127 (4): 467-470. PubMed.
2. ^ ^{a b} Bofill-Mas, S., Formiga-Cruz, M., Clemente-Casares, P., Calafell, F. and Girones, R. (2001). "Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA". J. Virol. 75 (21): 10290-10299. PubMed.
3. ^ Pavesi, A. (2005). "Utility of JC polyomavirus in tracing the pattern of human migrations dating to prehistoric times.". J. Gen. Virol. 86 (Pt 5): 1315-1326. PubMed.
4. ^ Monaco, M.C., Jensen, P.N., Hou, J., Durham, L.C. and Major, E.O. (1998). "Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection". J. Virol. 72 (12): 9918-9923. PubMed.
5. ^ Ricciardiello, L., Laghi, L., Ramamirtham, P., Chang, C.L., Chang, D.K., Randolph, A.E. and Boland, C.R. (2000). "JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract". Gastroenterology 119 (5): 1228-1235. PubMed.
6. ^ Elphick, G.F., Querbes, W., Jordan, J.A., Gee, G.V., Eash, S., Manley, K., Dugan, A., Stanifer, M., Bhatnagar, A., Kroeze, W.K., Roth, B.L. and Atwood, W.J. (2004). "The human polyomavirus, JCV, uses serotonin receptors to infect cells". Science 306 (5700): 1380-1383. PubMed.
7. ^ White, F.A., 3rd., Ishaq, M., Stoner, G.L. and Frisque, R.J. (1992). "JC virus DNA is present in many human brain samples from patients without progressive multifocal leukoencephalopathy". J. Virol. 66 (10): 5726-5734. PubMed.
8. ^ Theodoropoulos, G., Panoussopoulos, D., Papaconstantinou, I., Gazouli, M., Perdiki, M., Bramis, J. and Lazaris, ACh. (2005). "Assessment of JC polyoma virus in colon neoplasms". Dis. Colon. Rectum. 48 (1): 86-91. PubMed.

The boxed warning for the drug rituximab (Rituxan, co-marketed by Genentech BioOncology and Biogen Idec) includes that JC virus infection resulting in progressive multifocal leukoencephalopathy and death has been reported in patients treated with the drug:

http://www.gene.com/gene/products/information/pdf/rituxan-prescribing.pdf