title: BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist.
abstract: BACKGROUND
  Hemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with BK virus (BKV) reactivation manifested as BK viruria. However, since 77-90% of all adult BMT patients excrete BKV, viral reactivation alone cannot be responsible for HC. Recently, a significant overrepresentation of C-->G mutations in the Sp1 binding site in the non-coding control region (NCCR) of BKV was shown to be present in HC patients and absent in non-HC patients.
  
  
  OBJECTIVE
  We aimed to investigate if this mutation resulted in excessive BKV excretion in HC patients.
  
  
  METHODS
  A Real-Time PCR was developed and used to quantify BKV in urine samples from 21 patients with HC, with and without the mutations, as well as from patients without HC.
  
  
  RESULTS
  Quantification of BKV was successful in 18 of 21 urine patients (six with and six without C-->G mutations) and six patients without HC. A mean of 3.0 x 10(6) BKV copies/microl was detected in urine samples of HC patients with C-->G mutations, compared to a mean of 1.5 x 10(6) BKV copies/microl in HC patients without C-->G mutations and a mean of 1.0 x 10(6) BKV copies/microl in patients without HC. The obtained differences were however not statistically significant, due to one individual non-HC patient with an extremely high BKV copy number. Nevertheless, while 50% of the samples in the HC groups expressed 1 x 10(6) copies/microl or more, only one of the samples in the non-HC group contained a virus quantity higher than 5 x 10(5) copies.
  
  
  CONCLUSIONS
  Although we could not confirm that the C-->G mutations in the Sp1 site of BKV were responsible for an increased viral load in patients with HC, our data suggest that levels of BKV above 10(4) copies/microl may indicate a risk for HC.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Cancer Center Karolinska, CCK R8:01, 171 76 Stockholm, Sweden. peter.priftakis@cck.ki.se
authors.forename: Peter
authors.initials: P
authors.lastname: Priftakis
authors.forename: Gordana
authors.initials: G
authors.lastname: Bogdanovic
authors.forename: Parviz
authors.initials: P
authors.lastname: Kokhaei
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
mesh_terms: D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification*; D001665:Binding Sites / Q000235:genetics; D016026:Bone Marrow Transplantation; D003199:Computer Systems; D003556:Cystitis / Q000175:diagnosis / Q000821:virology*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000652:urine*; D006470:Hemorrhage / Q000821:virology; D006801:Humans; D016867:Immunocompromised Host; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000652:urine* / Q000821:virology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014184:Transplantation, Homologous; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000652:urine* / Q000821:virology; D014556:Urine / Q000821:virology; D014775:Virus Activation
chemical_list: D004279:DNA, Viral; D016329:Sp1 Transcription Factor