Assay Sheet
Test ID
3600 JCV Ultrasensitive Real-time qPCR
CPT Code
87799
Clinical Utility
JCV is the etiologic agent of progressive multifocal leukoencephalopathy (PML) which is mainly seen in HIV patients, organ transplant patients, and other immunodeficient syndromes. In addition to PML, JCV also causes nephropathy in the renal transplant setting, although with considerably less frequency than BKV. JCV should always be considered in an immunocompromised patient with progressively deteriorating CNS function. Quantitative JCV DNA PCR can be used to detect JCV in CSF in the setting of CNS disease, and blood and urine in the setting of renal dysfunction. Quantitative DNA PCR can be used to track the course of infection as well as monitor response to treatment.
Procedure
Extraction of JCV DNA from CSF followed by amplification and detection using real-time, quantitative PCR. An internal control is added to ensure the extraction was performed correctly and the PCR reaction was not inhibited. ViraCor's assay design includes multiple targets to account for viral mutations, which exponentially reduces the chance of false negative results.
Specimens
CSF: 1.5 ml minimum in sterile, screw-cap tube. Freeze prior to shipment. Ship on dry ice.
Causes for rejection
Call ViraCor at 800-305-5198 if specimen is greater than 96 hrs old.
Specificity
The primers and probes used in this assay are specific for all known JCV strains based on similarity search algorithms. Additionally, no cross reactivity was detected when tested against adenoviruses, BKV, CMV, EBV, HSV-1, HSV-2, HHV-6 variant A, HHV-6 variant B, HHV-7, HHV-8, parvo B19, SV-40, and VZV.
JC Virus Assay Range
25 copies/ml to 1x1010 copies/ml. Qualitative results will be provided for specimens positive between 25 copies/ml and 99 copies/ml. Quantitative results will be provided for specimens positive greater than or equal to 100 copies/ml.
Turnaround Time
Same day (within 8 to 12 hours of receiving specimen), Monday through Saturday
Shipping
Ship Monday through Friday. Friday shipments must be labeled for Saturday delivery. All specimens must be labeled with patient's name and collection date. Ship specimens Fed Ex Priority Overnight® to:
ViraCor Laboratories, 1001 NW Technology Dr, Lee's Summit, MO 64086
The CPT codes provided are based on ViraCor's interpretation of the American Medical Association's Current Procedural Terminology (CPT) codes and are provided for informational purposes only. CPT coding is the sole responsibility of the billing party. Questions regarding coding should be addressed to your local Medicare carrier. ViraCor assumes no responsibility for billing errors due to reliance on the CPT codes illustrated in this material. PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc. This assay was developed and the performance characteristics were determined at ViraCor Laboratories. This test is performed in a CLIA certified laboratory. FDA approval is not required for the performance of this test.
0509 V1
Pathogen Overview
ABOUT JC VIRUS
The JC virus (JCV) is a member of the Polyomaviridae family, which consists of small, nonenveloped viruses with a closed, circular double-stranded DNA genome. Polyomaviruses are ubiquitous in nature and can be isolated from a number of species. The human polyomaviruses were first isolated in 1971 and named JC and BK after the initials of the patients in whom they were first discovered. JCV was isolated from the brain tissue of a patient with progressive multifocal leukoencephalopathy (PML). BKV and JCV share 75% homology at the nucleotide sequence level. JCV is the etiologic agent of PML, which only occurs in immunocompromised hosts.
JC VIRUS CLINICAL MANIFESTATIONS
An estimated 60-80% of adults in Europe and the United States have antibodies to JCV. JCV and BKV are believed to circulate independently. JCV appears to be acquired later in childhood than BKV, at 10 to 14 years versus 3 to 4 years, respectively. Evidence is unclear regarding the transmission of JCV and the course of events during primary infection. Currently, there is no acute disease associated with JCV primary infection. It is proposed that JCV establishes a latent infection in the kidney following a primary infection, similar to BKV. Some evidence indicates latency also develops in the central nervous system (CNS). In-situ DNA hybridization has demonstrated JCV in B lymphocytes, bone marrow, lung, spleen, lymph node tissue and tonsillar tissue.
Progressive multifocal leukoencephalopathy (PML) is a rapidly progressing, extremely debilitating demyelination disease caused by infection of the central nervous system with JCV. It usually occurs in patients with diminished T cell function. PML is characterized by neurological deficits that progress rapidly, including hemiparesis, cognitive disturbance, visual field deficits, ataxia, aphasia, cranial nerve deficits, and sensory deficits. Patients who have PML typically deteriorate rapidly and death commonly occurs within 6 months of diagnosis, however, a subset of patients will experience fluctuating symptomology over a 2 to 3 year period.
PML is a rare disease that almost always occurs in the setting of significant immunosuppression, more specifically, in the setting of abnormalities of cell-mediated immunity. Prior to the AIDS epidemic, lymphoproliferative disorders were the most common predisposing illnesses accounting for described cases of PML. Only 230 cases were described between 1958 and 1984. The AIDS pandemic dramatically changed the demography of PML. Prior to the adoption of highly active antiretroviral therapy (HAART) in 1996, approximately 5% of all HIV-infected patients developed PML. More recently, PML has been documented in a few patients receiving certain monoclonal antibodies, natalizumab and rituximab, for the treatment of several auto-immune disorders and B-cell lymphomas, respectively. The virus’ exact mechanism of entry into the CNS is not understood at this time.
There are a few reported cases in the literature of JCV causing nephropathy in renal transplant patients, much like BKV. However, this appears to be unusual.
Several studies have demonstrated that the virus is often present in the urine of up to 70% of the subjects studied, but generally it is not found in blood, saliva, nasopharyngeal aspirates, or throat washings of either healthy subjects or HIV patients. In the case of PML patients, the virus appears to be present in the blood in very low titers, but present in CSF in high titers.
JC VIRUS LABORATORY DIAGNOSIS
The presence of JCV is detectable using a sensitive and specific quantitative real-time polymerase chain reaction (PCR) assay, which can be performed on a variety of specimen types, such as CSF, urine, blood, and organ biopsies. However, it is important to ascertain if the molecular assay being used is specific to JCV or if it cross reacts with BKV. The 2 viruses share a high level of homology, and many molecular assays are unable to differentiate between the two. The ViraCor JCV assay was carefully developed to be specific for JCV and not cross react with BKV.
JC VIRUS TREATMENT
Currently, there is not a specific antiviral therapy proven effective for JCV. Current treatment of immunocompromised patients consists of restoring cell-mediated immunity to the greatest extent possible. Cidofovir is currently being studied as a treatment option for transplant patients, and cytarabine can be used in the treatment of PML, although there is conflicting data regarding the efficacy of the latter.
Selected References
Berger J, Miller C, Mootoor Y, Avdiushko S, Kryscio R, Zhu H. JC virus detection in bodily fluids: clues to transmission. Clin Infect Dis. 2006;(43):e9-e12.
Berger JR., Natalizumab and progressive multifocal leukoencephalopathy. Ann Rheum Dis. 2006;65(Suppl III); iii48-iii53.
Demeter LM. JC, BK, and other polyomaviruses; progressive multifocal leukoencephalopathy. In: Mandell GL, Bennett JE, Dolin, eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. Vol 2. 4th ed. New York, NY: Churchill Livingstone; 1995:1400-1406.
deViedina DG, Infantes MD, Miralles P, Berenguer J, Marin M, et al. JC virus load in progressive multifocal leukoencephalopathy: analysis of the correlation between the viral burden in cerebrospinal fluid, patient survival, and the volume of neurological lesions. Clin Infect Dis. 2002;(34):1568-1575.
Knipe D, Howley P. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
Salmaggi A, Maccagnano E, Castagna A, Zeni S, Fantini F, et al. Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythromatosus and progressive multifocal leukoencephalopathy. Neurol Sci. 2001;(22):17-20.
PAO-11-0707 PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc.
