JC virus
| JC virus | |
|---|---|
| Virus classification | |
| Group: | Group I (dsDNA) |
| Family: | Polyomaviridae |
| Genus: | Polyomavirus |
| Species: | JC polyomavirus |
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 using 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).
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[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][3][4] It is found in high concentrations in urban sewage worldwide, leading some researchers to suspect contaminated water as a typical route of infection.[5]
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.[6]
[edit] Infection and pathogenesis
The initial site of infection may be the tonsils,[7] or possibly the gastrointestinal tract.[5] The virus then remains latent in the gastrointestinal tract [8] and can also infect the tubular epithelial cells in the kidneys,[9] 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-HT2A serotonin receptor.[10] JC viral DNA can be detected in both non-PML affected and PML-affected (see below) brain tissue.[11]
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.[12] 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.[13]
[edit] Drugs associated with reactivation
Since immunodeficiency causes this virus to progress to PML, immunosuppressants are contraindicative to those infected.
The boxed warning for the drug rituximab (Rituxan, co-marketed by Genentech BioOncology and Biogen Idec) includes a statement that JC virus infection resulting in progressive multifocal leukoencephalopathy, and death has been reported in patients treated with the drug.[14]
The boxed warning for the drug natalizumab (Tysabri, marketed by Elan and developed by Biogen Idec) includes a statement that JC virus resulted in progressive multifocal leukoencephalopathy developing in three patients who received natalizumab in clinical trials.
The boxed warning was added on 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 a statement 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.
A boxed warning for brentuximab vedotin (Adcetris) was issued by the FDA on January 13, 2011 after two cases of PML were reported, bringing the total number of associated cases to three.[15]
[edit] Treatments
In June 2010, the first case report appeared of a PML patient being successfully treated with mefloquine. Mefloquine is an antimalarial drug that can also act against the JC virus. Administration of mefloquine seemed to eliminate the virus from the patient's body and prevented further neurological deterioration.[16]
On November 30, 2010, Cytheris announced that they had eradicated the JC virus from a PML patient, using their human interleukin-7 investigational drug (CYT107) combined with Chimerix's investigational, orally-available lipid conjugate prodrug of Cidofovir (CMX001).[17]
[edit] References
- ^ BL, Walker DL et al (1971). "Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy". Lancet 1 (7712): 1257–60. doi:10.1016/S0140-6736(71)91777-6. PMID 4104715.
- ^ Hansjügen T. Agostini, Caroline F. Ryschkewitsch, Rachel Mory, Elyse J. Singer and Gerald L. Stoner (1997). "JC Virus (JCV) genotypes in brain tissue from patients with progressive multifocal leukoencephalopathy (PML) and in urine from controls without PML: increased frequency of JCV Type 2 in PML". The Journal of Infectious Diseases (Oxford University Press) 176 (1): 1–8. JSTOR 30107072.
- ^ Laura A. Shackelton, Andrew Rambaut, Oliver G. Pybus, and Edward C. Holmes (2006). "JC Virus evolution and its association with human populations". Journal of Virology (American Society for Microbiology) 80 (20): 9928–9933.. doi:10.1128/JVI.00441-06. PMC 1617318. PMID 17005670. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1617318.
- ^ 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. doi:10.1093/infdis/127.4.467. 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. doi:10.1128/JVI.75.21.10290-10299.2001. PMC 114603. PMID 11581397. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=114603.
- ^ 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. doi:10.1099/vir.0.80650-0. 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. PMC 110504. PMID 9811728. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=110504.
- ^ 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. doi:10.1053/gast.2000.19269. 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. doi:10.1126/science.1103492. 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. PMC 241447. PMID 1326640. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=241447.
- ^ 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. doi:10.1007/s10350-004-0737-2. PMID 15690663.
- ^ gene.com/gene/products/information/pdf/rituxan-prescribing.pdf
- ^ "Adcetris (brentuximab vedotin): Drug Safety Communication - Progressive Multifocal Leukoencephalopathy and Pulmonary Toxicity". U.S. FDA. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm287710.htm. Retrieved 14 January 2012.
- ^ Gofton TE, Al-Khotani1 A, O'Farrell B, Ang LC, McLachlan RS (2010). "Mefloquine in the treatment of progressive multifocal leukoencephalopathy". J Neurol Neurosurg Psychiatry 82 (4): 452–455. doi:10.1136/jnnp.2009.190652. PMID 20562463. http://jnnp.bmj.com/content/early/2010/06/19/jnnp.2009.190652.full.
- ^ "Cytheris Announces Publication of Clinical Case Study Combining Recombinant Human Interleukin-7 (CYT107) with Antiviral Agent CMX001 as Potential Treatment for Progressive Multifocal Leukoencephalopathy (PML)". BusinessWire. November 30, 2010. http://www.businesswire.com/news/home/20101130005169/en/Cytheris-Announces-Publication-Clinical-Case-Study-Combining. Retrieved October 22, 2011.
[edit] External links
- NCBI - JC Virus Complete Genome
- JC Brain infection MRI Diagnosis of PML
