Download PDF

Assay Sheet

Test ID

3000 SV-40 Real-time qPCR

CPT Code

87799

Clinical Utility

SV-40 is documented to have contaminated some polio vaccine preparations between 1955 and 1963. Epidemiological studies are underway attempting to prove a causal relationship between SV-40 and certain cancers such as mesothelioma, osteosarcoma, and non-Hodgkin’s lymphoma. Quantitative SV-40 DNA PCR can be used to test for the presence of SV-40 DNA in biological specimens.

Procedure

Extraction of SV-40 viral DNA from plasma, other biological fluids, or tissues 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.

Specimen type & specimen handling

Whole Blood: 4-5 mls collected in EDTA (lavender top) tube. Do not freeze; ship ambient. Testing will be performed on plasma separated from the submitted whole blood specimen. Whole blood specimens are accepted as a matter of convenience for the originating laboratory.

Plasma: Collect 4-5 mls whole blood in EDTA or ACD tube, centrifuge and transfer 2 mls plasma to sterile, screw top tube. Ship at ambient temperature Monday thru Friday. Specimen must be received within 96 hrs of collection. 

Tissue: Place in sterile, screw top container; add small amount of sterile saline to keep moist. Paraffin embedded tissue is acceptable.  Ship at ambient temperature Monday thru Friday. Fresh tissue must arrive within 96 hrs of collection.

Causes for Rejection

Whole blood frozen

Call ViraCor at 800-305-5198 if specimen is greater than 96 hrs old

Specimen types other than those listed above that were sent without prior authorization

SPECIFICITY

The primers and probes used in this assay are specific for SV-40 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, JCV, Parvovirus B19, and VZV.

SV-40 Assay Range

500 copies/ml to 1 x 10¹⁰ copies/ml

Tissue specimen results will be normalized to copies/1,000 cells  

Turnaround Time

Same day (within 8 to 12 hours of receiving specimen), Monday through Saturday

Shipping

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.

0909 V2

Pathogen Overview

ABOUT SV-40 VIRUS

SV-40 is a member of the Polyomaviridae family, along with BK virus (BKV) and JC virus (JCV). They are 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.

SV-40 was discovered in 1960 and has frequently been used in medical research because of its high oncogenicity and potent transforming capacity. It is unclear how SV-40 infection originated in humans, but it is known that potentially contaminated polio vaccines derived from rhesus monkey kidney cells were administered to approximately 98 million individuals in the United States between 1955 and 1963. It is estimated that up to one-third of these vaccines could have been contaminated with infectious SV-40. However, infections in individuals who did not receive polio vaccines and recent data supporting the transmission of HIV from monkeys to humans, suggest that other modes of transmission are involved.

SV-40 CLINICAL MANIFESTATIONS

SV-40 is asymptomatic in monkeys; however, it transforms cultured human cells and produces tumors when injected into newborn rodents. SV-40 DNA has been discovered in human tumors, specifically in mesotheliomas, brain tumors, osteosarcomas, choroids plexus tumors, and ependyomas. The presence of SV-40 in human mesotheliomas and other human tumors has been confirmed by the work of more than 26 research groups. However, the role of SV-40 as a pathogen in the human population continues to be debated.

There is little published data on the role of SV-40 infections in transplant patients. One report found specific neutralizing antibodies to SV-40 in 18% of adult renal transplant patients. More recently, clinical studies have isolated SV-40 in allografts of children who underwent renal transplantation, as well as in the blood, urine, and kidneys of patients with focal segmental glomerulosclerosis, a known cause of end stage renal disease.

SV-40 LABORATORY DIAGNOSIS

Serological analysis has proved helpful for epidemiological purposes, but is not conclusive in diagnosing clinical syndromes. Unfortunately, there is considerable cross reactivity between SV-40 and BKV antibodies. Real-time polymerase chain reaction (PCR) is a sensitive method for detecting the presence of SV-40 DNA, allowing further research into possible disease manifestations of the virus. Standardization of serological assays and molecular assays for SV-40 could assist researchers in understanding and drawing conclusions regarding the role of SV-40 in rare cancers.

Selected References

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.

Knipe D, Howley P. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.

Kwak EJ, Vilchez RA, Randhawa P, Shapiro R, Butel JA, et al. Pathogenesis and management of polyomavirus infection in transplant recipients. Clin Infect Dis. 2002;(35):1081-1087.

Rizzo P, Bocchetta M, Powers A, Foddis R, Stekala E, et al. SV-40 and the pathogenesis of mesothelioma.

Cancer Biol. 2001;(11):63-71.

Wong M, Pagano JS, Schiller JT, Tevethia SS, Raab-Traub N, et al. New associations of human papillomavirus, simian virus 40, and epstein-barr virus with human cancer. J Natl Cancer Inst. 2002;(94):1832-1836.

PAO-13-0707 PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc.

Abstracts & Publications

Kwak EJ, Vilchez RA, Randhawa P, et al. Pathogenesis and management of polyomavirus infection in transplant recipients. Clin Infect Dis. 2002;(35):1081-1087.

Polyomavirus (JC virus[JCV], BK virus [BKV], and simian virus 40 [SV40]) establish subclinical and persistent infections and share the capacity for reactivation from latency in their host under Immunosuppression. JCV establishes latency mainly in the kidney, and its reactivation results in the development of progressive multifocal leukoencephalopathy. BKV causes infection in the kidney and the urinary tract, and its activation causes a number of disorders, including nephropathy and hemorrhagic cystitis. Recent studies have reported SV40 in the allografts of children who received renal transplants and in the urine, blood, and kidneys of adults with focal segmental glomerulosclerosis, which is a cause of end-stage renal disease and an indication for kidney transplantation. Clinical syndromes related to polyomavirus infection are summarized in the present review, and strategies for the management of patients who receive transplants are discussed.

Rizzo P, Bocchetta M, Powers A, et al. SV-40 and the pathogenesis of mesothelioma. Semin Cancer Biol. 2001;(11):63-71.

Malignant mesothelioma, a tumor of the pleura, pericardium, and peritoneum, is presently a worldwide problem. Current therapy is ineffective in slowing the course of the disease, and median survival from the time of diagnosis is rarely greater than 1 year. While the tumor was almost unknown prior to the second half of the twentieth century, it is presently responsible for more than 2000 deaths per year in the US alone. Mesothelioma is frequently associated with exposure to asbestos, but the incidence of cases involving individuals with low levels of asbestos exposure is increasing. For this reason, there has been much interest in studying whether there are alternative factors that act alone or in conjunction with asbestos in producing this malignancy. In the last decade, simian virus 40 (SV40) has become the most notable suspected agent.

Wong M, Pagano JS, Schiller JT, et al. New associations of human papillomavirus, simian virus 40, and epstein-barr virus with human cancer. J Natl Cancer Inst. 2002;(94):1832-1836.

Approximately 15% of all cancers worldwide appear to be associated with viral infections, and several human DNA viruses are now accepted as causative factors of specific malignancies. Human papillomaviruses (HPVs) cause cervical and anogenital cancers. Epstein-Barr virus (EBV) causes infectious mononucleosis and is closely associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease. HPV is now associated with oral cancers, EBV with breast and gastric cancers, and simian virus 40 (SV40) with human mesothelioma and various brain and bone cancers. Several associations are not universally accepted, and their validity remains controversial. Consequently, the Biological Carcinogenesis Branch of the Division of Cancer Biology at the national Cancer Institute convened a workshop on March 12-13, 2001, in Bethesda, MD, to assess current knowledge concerning associations of HPV, SV40, and EBV with selected human cancers and to define areas where investigation is needed.