Overrepresentation of point mutations in the Sp1 site of the non-coding control region of BK virus in bone marrow transplanted patients with haemorrhagic cystitis

Background: Haemorrhagic cystitis (HC) in allogeneic bone marrow transplant ed (BMT) patients is associated with reactivation of BK virus (BKV) manifes ted as BK viruria. However, it has been suggested that BKV reactivation alo ne is not responsible for HC, since BKV can be detected in the urine of 50- 90% of all adult BMT patients. Objectives: In the present study, we analyse d if BK viruses with specific mutations in the non-coding control region (N CCR) or in the region encoding the major capsid protein (VP1) were more fre quently associated to the appearance of HC in BMT patients. Study design: T he NCCR and the region encoding VPI of BKV excreted in the urine from 25 BM T patients, 16 with and nine without HC. were sequenced by an ABI Prism Big Dye terminator cycle sequencing ready reaction kit. Results tmd Conclusion s: A statistically significant (P = 0.019) overrepresentation of C to G mut ations within the NCCR Spl binding site was observed in 7/16 (43%) patients with HC (six cases at position 249 (P = 0.035) and one case at position 25 1), as compared with 0/9 (0%) of the patients without HC. Major differences were not observed in the VP1 sequences of patients with and without HC. BK V WW and WWT-variants as well as BKV subtype I were most commonly encounter ed in both groups of patients. In conclusion. C to G point mutations, withi n the BKV NCCR Spl binding site, were significantly more common in patients with HC, suggesting that these mutations may be indicative for the clinica l diagnosis of HC and could influence the virulence of the virus. (C) 2001 Elsevier Science B.V. All rights reserved.