JC virus Information & JC virus Links at HealthHaven.com

JC virus
Virus classification
Group:	Group I (dsDNA)
Family:	Polyomaviridae;
Genus:	Polyomavirus;
Species:	JC polyomavirus;

The JC 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).^[1] The virus causes PML and other diseases only in cases of immunodeficiency, as in AIDS or during treatment with drugs intended to induce a state of immunosuppression (e.g. organ transplant patients).

[edit] 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 ^[2]. It is found in high concentrations in urban sewage worldwide, leading some researchers to suspect contaminated water as a typical route of infection ^[3].

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 ^[4].

[edit] Infection and pathogenesis

The initial site of infection may be the tonsils,^[5] or possibly the gastrointestinal tract.^[3] The virus then remains latent in the gastrointestinal tract ^[6] and can also infect the tubular epithelial cells in the kidneys,^[7] 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.^[8] JC viral DNA can be detected in both non-PML affected as well as PML-affected (see below) brain tissue.^[9]

Immunodeficiency or immunosuppression allows JCV to reactivate. In the brain it causes the usually fatal progressive multifocal leukoencephalopathy, or PML, by destroying oligodendrocytes. Whether this represents the reactivation of JCV within the CNS or seeding of newly reactivated JCV via blood or lymphatics is unknown.^[10] 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.^[11]

[edit] Drug interactions

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 [1].

The boxed warning for the drug natalizumab (Tysabri, marketed by Elan and developed by Biogen Idec) includes that JC virus resulted in progressive multifocal leukoencephalopathy developing in three patients who received natalizumab in clinical trials.

The boxed warning was added Feb. 19, 2009 for the drug efalizumab (Raptiva, marketed in the U.S. by Genentech, and marketed in Europe by Swiss drugmaker Merck Serono) includes that JC virus resulting in progressive multifocal leukoencephalopathy developed in three patients who received efalizumab in clinical trials. The drug was pulled off the U.S. market because of the association with PML on April 10, 2009.

[edit] References

^ BL, Walker DL, Zu Rhein GM et al. "Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy." Lancet. 1971; 1:1257-60. PMID 4104715
^ 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. PMID 4571704.
^ ^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. PMID 11581397.
^ 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. PMID 15831942.
^ 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. PMID 9811728.
^ 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. PMID 11054380.
^ Harvey, R. (2007) Microbiology Philadelphia, Lippincott Williams & Wilkins.
^ 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. PMID 15550673.
^ 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. PMID 1326640.
^ http://www.emedicine.com/neuro/topic450.htm
^ 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. PMID 15690663.

[edit] External links

NCBI - JC Virus Complete Genome

[0] BL, Walker DL, Zu Rhein GM et al. "Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy." Lancet. 1971; 1:1257-60. PMID 4104715

[Padget-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. PMID 4571704.

[Bofill-2] 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. PMID 11581397.

[Pavesi-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. PMID 15831942.

[Monaco-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. PMID 9811728.

[Ricardiello-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. PMID 11054380.

[6] Harvey, R. (2007) Microbiology Philadelphia, Lippincott Williams & Wilkins.

[Elphick-7] 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. PMID 15550673.

[White-8] 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. PMID 1326640.

[9] ttp://www.emedicine.com/neuro/topic450.htm

[Theodoropoulos-10] 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. PMID 15690663.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

Contents

[edit] Epidemiology

[edit] Infection and pathogenesis

[edit] Drug interactions

[edit] References

[edit] External links