JC virus or John Cunningham virus (JCV) & BK virus (BKV): The human polyomaviruses BK virus (BKV) and JC virus (JCV) are ubiquitous and infect a high proportion of the population. Primary infection occurs during childhood and is usually inapparent but may be accompanied by mild respiratory illness. During primary infection, there is viremia and the virus is transported to the kidney, where it persists indefinitely. Immunocompromising conditions result in reactivation of virus and viruria. Polyomavirus viruria has been documented most extensively in recipients of renal allografts and bone marrow transplants and in pregnant women. JCV is neurotropic and produces progressive multifocal leukoencephalopathy, a fatal neurological disease, in individuals with immunological deficits. BKV is associated with ureteral stenosis in renal allograft recipients and hemorrhagic cystitis in recipients of bone marrow transplants. BKV genomes have been frequently recovered from tumors of the brain and pancreatic islet cells. Primary infection with this double-stranded DNA virus is generally asymptomatic and occurs in childhood. The most common symptoms, when symptoms are noted, are fever and nonspecific upper respiratory infection. After primary infection has occurred, the virus can remain latent in many sites, most notably the kidney Transmission may occur by means of exposure to bodily fluids, such as oral secretions, or via transplacental passage. In states of relative or absolute cellular immunodeficiency, the virus can become reactivated and cause disease. Primary polyomavirus infections have not been associated with any specific clinical syndromes. Most infections seem to be sub-clinical although some children developed mild respiratory symptoms and others had cystitis. It is thought that primary BKV infections may on occasions be associated with either acute respiratory
Disease or cystitis but further work is required.
- Progressive multifocal leucoencephalopathy – JC virus is now firmly associated with PML. It has not been established whether PML is the result of a primary infection with JCV in a person with impaired immunity or whether it follows reactivation of latent virus. The fact that PML is relatively uncommon
in children and young persons and more often develops in people in the fifth and sixth decades of life suggests that latent virus is the more likely cause. The pathogenesis of PML is not fully understood but it is postulated that in patients with disorders of immunoregulation, polyomaviruses arenolongercontained in a latent state and replicate within the oligodendrocytes, causing the destruction of the cell and the breakdown of the myelin sheath. PML is a unique demyelinating disease which usually occurs in a person with abnormal immune responses resulting from serious disease, treatment with cytotoxic drugs or irradiation, or long term immunosuppression. The pathology of PML
is distinctive and consists of multiple foci of demyelination of varying size from pinpoint lesions to areas of several centimetres. The lesions may occur anywhere but are usually in the cerebral hemispheres, less often in the cerebellum and brain stem and rarely in the spinal cord. The oligodendrocytes in the peripheral zone surrounding an area of demyelination are grossly abnormal. The nuclei of abnormal oligodendrocytes are packed with JC virions. Typically, PML evolves gradually, with impairment of mental function and disturbance of speech and vision. Movement may also be affected. The disease then progresses rapidly and the patient is severely disabled, eventually becoming demented, blind and paralyzed and finally coma and death. PML is frequently associated with lymphoproliferative and other chronic diseases, such as AIDS, Hodgkin’s disease, CLL, sarcoidosis, TB, SLE and organ transplantation. Only rarely has PML been reported occurring spontaneously in an apparentlyhealthyperson.Occasionally, PML may spontaneously arrest. PML has been reported in children with congenital severe combined immunodeficiency which suggests that a primary JCV infection is responsible.
- Ureteric stenosis in renal transplant recipients – the only other disease with which ureteric stenosis have been associated is ureteric stenosis in renal transplant patients. The polyomavirus infection induces proliferation of the transitional epithelial cells in the ureter and this can lead to partial obstruction or actual stricture formation. The affected cells had inclusion bodies. 9 cases have been recognized and both JC and BK have been implicated. The ureteric obstruction occurred between 50 to 300 days post-transplant.
- Other possible associations – BK virus was associated with cases of acute haemorrhagic cystitis following bone marrow transplantation. However, it is possible that two independent but synchronous events may be taking place – reactivation of BKV and haemorrhagic cystitis. The genomes of JC and BK
Viruses were detected in several tumours, but there is no evidence that human polyomaviruses are associated with the causation of any tumours.
Methodology: Taqman Real time PCR assay
- Monitor disease state in solid organ transplant and HIV patients
- Assist in JC/BK diagnosis and patient management
- Identify JC/BK viral load quantitation for epidemiologic and prognostic purposes
- Assess viral response to treatment as measured by changes in the JC/BK DNA levels
- Rapid test to diagnose JC/BK in immunocompromised patients or solid organ donors
Performed: Every day
Reported: 2-3 days
Specimen required: Urine, C.S.F. Serum, plasma Collect in: Lavender (EDTA), pink (K2EDTA), or serum separator .Stability collection to initiation of testing On Cells: Ambient: 4 hours; after separation from cells: Refrigerated: 48 hours; Frozen at -20°C: 72 hours; Frozen at -70°C: 4 months. Do not thaw avoid repeated freezing and thawing
Specimen Preparation: Separate serum or plasma from cells within 24 hours.
Storage/Transport Temperature: Frozen-20 0C. Refrigerate specimens at 2°C-4°C.
Unacceptable Conditions: Heparinized specimens, Hemolysis sample, Quantity not sufficient for analysis, specimen grossly contaminated, specimen too old, frozen whole blood specimen, specimen leaky or tube broken.
Interpretation: This test can quantitative/detect JC / BK over the range 110-108 Copies/mL. However this does not mean that lower copies or higher copies cannot be detected. The lower copies can be detected in some cases. This is a limitation of the currently available extraction systems. The test is intended for use in conjunction with clinical presentation and other markers as an aid in assessing viral response to antiviral treatment as measured by change in JC / BK DNA levels. A negative result does not preclude the presence of JC / BK infection because results depend on adequate/proper patient sample storage and transportation.
The result of this test must always be correlated with clinical status and history of the patient and other relevant data and should not be used alone for the interpretation.
Note: The test is intended for use in conjunction with clinical presentation and other laboratory markers as an indicator of disease prognosis. This test is also used as an aid in assessing viral response to antiretroviral treatment as measured by changes in JC / BK DNA levels