The JC virus or John Cunningham virus is a type of human polyomavirus and is genetically
similar to BK virus and SV40.
It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman
and Rubinstein, and later isolated in culture and named using the two initials of a patient
with progressive multifocal leukoencephalopathy.
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.
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.
It is found in high concentrations in urban sewage worldwide, leading some researchers
to suspect contaminated water as a typical route of infection.
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.
14 subtypes or genotypes are recognised each associated with a specific geographical region.
Three are found in Europe.
A minor African type—Af1—occurs in Central and West Africa.
The major African type—Af2—is found throughout Africa and also in West and South Asia.
Several Asian types are recognised B1-a, B1-b, B1-d, B2, CY, MY and SC.
An alternative numbering scheme numbers the genotypes 1–8 with additional lettering.
Types 1 and 4 are found in Europe and in indigenous populations in northern Japan, North-East
Siberia and northern Canada.
These two types are closely related.
Types 3 and 6 are found in sub-Saharan Africa: type 3 was isolated in Ethiopia, Tanzania
and South Africa.
Type 6 is found in Ghana.
Both types are also found in the Biaka Pygmies and Bantus from Central Africa.
Type 2 has several variants: subtype 2A is found mainly in the Japanese population and
native Americans; 2B is found in Eurasians; 2D is found in Indians and 2E is found in
Australians and western Pacific populations.
Subtype 7A is found in southern China and South-East Asia.
Subtype 7B is found in northern China, Mongolia and Japan Subtype 7C is found in northern
and southern China.
Subtype 8 is found in Papua New Guinea and the Pacific Islands.
Infection and pathogenesis The initial site of infection may be the tonsils,
or possibly the gastrointestinal tract.
The virus then remains latent in the gastrointestinal tract and can also infect the tubular 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.
JC viral DNA can be detected in both non-PML affected and PML-affected brain tissue.
JCV found in the central nervous system of PML patients almost invariably has differences
in promoter sequence to the JCV found in healthy individuals.
It is thought that these differences in promoter sequence contribute to the fitness of the
virus in the CNS and thus to the development of PML.
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.
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.
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 includes a statement that JC virus infection resulting
in progressive multifocal leukoencephalopathy, and death has been reported in patients treated
with the drug.
The boxed warning for the drug natalizumab 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 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 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.
References
Zu Rhein, G.M.; Chou, S.M..
Science 148: 1477–1479.
doi:10.1126/science.148.3676.1477.
Silverman, L.; Rubinstein, L.J.. Acta Neuropathologica 5: 215–224.
doi:10.1007/bf00686519.
External links NCBI—JC Virus Complete Genome
JC Brain infection MRI Diagnosis of PML