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Progressive multifocal leukoencephalopathy causes

Introduction

This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Progressive multifocal leukoencephalopathy.
Overview

Overview

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). The virus is widespread, with 86% of the general population presenting antibodies, but it usually remains latent, causing disease only when the immune system has been severely weakened. The virus causes PML and other diseases only in cases of immunodeficiency, as in AIDS, or immunosuppression, as in organ transplant patients.

Epidemiology

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

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-HT2A 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

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. PMID 4571704.
  2. ↑ 2.0 2.1 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.
  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.
  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.
  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. ↑ 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.
  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. PMID 1326640.
  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. PMID 15690663.
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References

References

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]