Genetic variability in BK Virus regulatory regions in urine and kidney biopsies from renal-transplant patients.

The human Polyomavirus BK (BKV) contains a hypervariable non-coding control region (NCCR), which regulates DNA replication and RNA transcription. The aim of this study was to characterize BKV NCCR-variants in kidney biopsies and urine samples from renal-transplant patients and to see whether there is any association between NCCR variability and BKV-nephropathy. Kidney biopsies and urine samples were examined from 11 patients with elevated serum creatinine and >5,000 genomic BKV copies per ml of urine. BKV-nephropathy was diagnosed in seven patients. Using PCR, BKV NCCR was amplified from urine from all BKV-nephropathy patients. The dominant NCCR corresponded to the archetype (WWT). In addition, a total of 14 non-archetype NCCR-variants were detected. Thirteen of these NCCR-variants were found in urine from one single BKV-nephropathy patient also suffering from hepatitis C. The NCCR of BKV was amplified from kidney biopsies of six BKV-nephropathy patients. Three patients demonstrated WWT NCCR, while three other patients harbored rearranged NCCR variants. The WWT NCCR was also detected in urine from control patients, except for one patient who harbored two non-archetypal NCCR variants. However, these variants were not resulting from complex rearrangements but instead had a linear NCCR anatomy with deletion(s) in the P-block. No BKV DNA was detected in biopsies from control patients. The results indicate that rearranged BKV NCCR is associated with BKV-nephropathy.