Quantitated PCR Control DNA for Human Polyomaviruses: JCV and BKV

Advanced Biotechnologies Incorporated (ABI) introduces quantitated PCR control DNA for human Polyomaviruses: JCV, catalog #08-943-250, and BKV, catalog #08-942-250.

JC virus/JCV was first isolated in 1971 from the brain tissue of a Hodgkins lymphoma patient (JC) with the demyelinating disease of the brain, progressive multifocal leukoencephalopathy (PML). BK virus/BKV was first isolated in 1970 from the urine of a renal allograft recipient (BK) with ureteric stricture.

JCV and BKV belong to the Family: Polyomaviridae, and Genus: Polyomavirus. Virions are nonenveloped, 40 nm in diameter containing supercoiled double-stranded DNA of ~5.13 kb, and have an icosahedral capsid composed of 72 capsomeres. Three structural proteins, VP 1, VP 2, and VP 3, make up the virus capsid, with VP 1 being the major component. JCV and BKV share ~70% homology in their DNA sequences.

Both JCV and BKV infections are transmitted from human to human (probably through the respiratory system), establish viremia, settle in the kidneys, and remain latent in the host. The main site of latency for JCV is B lymphocytes and for BKV is uroepithelial cells.

Seroepidemiological studies revealed that in the USA, 50% of children develop antibodies to BKV by 3–4 years of age, and to JCV by 10–14 years of age. The primary BKV infection in immunocompetent children usually causes mild respiratory illness and, rarely, cystitis. However, in immunodeficient children, BKV might cause glomerulonephritis leading to renal failure. Reactivated BKV infection may cause symptomless viruria. The primary JCV infection in immunodeficient children may cause PML.

The pathogenic effects of JCV and BKV are evident only in immunocompromised individuals due to the reactivation of latent virus in the kidney and/or lymphocytes. JCV is the etiological agent of PML, the only known human viral demyelinating disease of the central nervous system, and is more frequently seen in AIDS patients (~70%). In PML patients, JCV DNA is detected in brain tissue and cerebrospinal fluid (CSF) as well as an elevated level of JCV/VP 1 specific antibody.

BKV infection is associated with cystitis, interstitial nephritis, ureteric stenosis, kidney failure in renal allograft recipients, and hemorrhagic cystitis and pulmonary infection in bone marrow transplant (BMT) recipients. The use of potent immunosuppressive drugs in renal transplant recipients has led to the emergence of the “BKV Nephropathy Syndrome” in ~8% of the kidney transplant recipients1, which is characterized by transplanted kidney dysfunction and graft loss. JCV viruria and, more commonly, BKV viruria have been found in ~38-47% of BMT recipients.

Both JCV and BKV are tumorigenic in rodents, but conclusive evidence for their association with human cancers is yet to emerge2.

Laboratory diagnosis of JCV infection can be established by the detection of viral DNA by PCR, viral antigens in tissues by immunohistochemistry (IHC), and in situ hybridization using JCV DNA as probe.

The detection of JCV DNA by PCR in brain tissues or CSF of PML patients is sensitive (90%) and specific (95-98%). High copy numbers are used as prognostic indicators of the progression of the disease; low or undetectable amounts of DNA predict long-term survival of PML patients.

The definitive diagnosis of BKV infection can be established by: histopathologic detection of basophilic intranuclear viral inclusion bodies in tubular epithelial cells of kidney biopsy tissues or by urinary cytology, detection of viral antigens by IHC, electron microscopy for the detection of viral particles in biopsy tissues, and detection of BKV DNA by PCR in blood, urine, and/or kidney biopsy tissues. The measurement of viral load (DNA copy numbers) by quantitative PCR analysis is a useful tool in monitoring the clinical course of BKV infection as well as in monitoring the response of patients to antiviral therapy.

The search for potent and efficacious antiviral drugs against JCV and BKV is ongoing.

References:
Mayor, E.O., Human Polyomavirus. In: Fields Virology, Fourth Edition,Volume 2, Chapter 64, p.2175–2196, 2001. Lippincott Williams
& Wilkins, Philadelphia, PA. 19106, USA.
1. Randhawa, P., et.al., Correlates of quantitative measurement of BK Polyomavirus (BKV) DNA with clinical course of BKV infection in
renal transplant patients. J.Clin.Micro., 42: 1176–1180, 2004.
2. Valle, L.D., et.al., Primary central nervous system lymphoma expressing the human neurotropic Polyomavirus, JC virus, genome.
J.Virol., 78: 3462–3469, 2004.