BK virus (BKV), originally described in 1971 , is a 5kb polyomavirus which shares roughly 75% of its DNA sequence with JC virus (JCV). Nearly 80% of the population is seropositive for these viruses [2, 5-6]. Although BKV disseminates into the urinary tract and kidneys, it usually remains latent . However, immunocompromised patients, such as those undergoing kidney or multiple organ transplants , severe reactions as a result of BKV infection may occur. The infection presents itself in the clinic as renal dysfunction and abnormal urinalysis. If the BK virus replicates within the new graft, BK-associated nephropathy (BKVAN) may arise . BKVAN is thought to occur as a result of high doses of immunosuppressants administered to transplant patients that also have BKV infections (1-10% of kidney transplant patients). The devastating consequence of BKVAN is graft rejection, which occurs in up to 80% of infected patients. Therefore, in order to determine an optimal immunosuppressant dosing regimen, accurate measurement of BK viral load in transplant patients is needed.
JCV also arises in immunocompromised patients: AIDS, transplant, those undergoing treatment for cancer, MS, psoriasis, or those with Hodgkin’s Lymphoma. JCV can cause progressive multifocal leukoencephalopathy (PML), a progressive, demyelinating disease that often becomes fatal. Currently, there is no therapy for JCV and labs monitor viral load and adjust immunosuppressant dose.Providing a DNA reference material for BK virus will not only allow this, but also enable commutability of measurements among laboratories across the world.
 Gardner SD, et al, 1971. "New human papovavirus (B.K.) isolated from urine after renal transplantation". Lancet. 1 (7712): 1253-7.
 Egli A, et al, 2009. "Prevalence of Polyomavirus BK and JC Infection and Replication in 400 Healthy Blood Donors". Journal of Infectious Disease. 199: 837-46. Gupta, G, et al, 2006. “Low Incidence of BK Virus nephropathy after simultaneous kidney pancreas transplantation”. Transplantation. 82 (3): 382-8.
 Fishman, JA, 2002. "BK Virus Nephropathy - Polyomavirus Adding to Injury". New England Journal of Medicine. 347 (7) 527-530.
 Kean, Jaime M., et. al, 2009. "Seroepidemiology of Human Polyomaviruses". PLoS Pathogens. 5 (3): e1000363.
 Egli, Adrian, et. al, 2009. "Prevalence of Polyomavirus BK and JC Infection and Replication in 400 Healthy Blood Donors". The Journal of Infectious Diseases. 199 (6): 837–46.
The goal of this project is to provide an SI-traceable reference material for use by calibrant and reagent manufacturers in production of their own calibrants and standards. Clinical laboratories with in-house methods will be able to use the reference material for production of their own quality control materials, which will be traceable to a NIST standard.
Whole BKV or JCV virus genomes will be inserted into a cloning vector, propagated in Escherichia coli, extracted, linearized, and certified for number of copies of the genome per volume (e.g. copies per microliter). The DNA will be sequenced and provided as information value in the certificate of analysis.
Start Date:December 1, 2010
Lead Organizational Unit:mml
Viral testing manufacturers, clinical testing community
Organizations: Quality Control for Molecular Diagnostics, Association for Molecular Pathology, National Institute of Biological Standards and Control (UK), University of Washington, Genewiz.
Dr. Peter M. Vallone