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 transplanted (BMT) patients is associated with reactivation of BK virus (BKV) manifested as BK viruria. However, it has been suggested that BKV reactivation alone is not responsible for HC, since BKV can be detected in the urine of 50-90% of all adult BMT patients.


OBJECTIVE
In the present study, we analysed if BK viruses with specific mutations in the non-coding control region (NCCR) or in the region encoding the major capsid protein (VP1) were more frequently associated to the appearance of HC in BMT patients.


METHODS
The NCCR and the region encoding VP1 of BKV excreted in the urine from 25 BMT patients, 16 with and nine without HC, were sequenced by an ABI Prism Big Dye terminator cycle sequencing ready reaction kit.


CONCLUSIONS
A statistically significant (P=0.019) overrepresentation of C to G mutations within the NCCR Sp1 binding site was observed in 7/16 (43%) patients with HC (six cases at position 249 (P=0.035) and one case at position 251), 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. BKV WW and WWT-variants as well as BKV subtype I were most commonly encountered in both groups of patients. In conclusion, C to G point mutations, within the BKV NCCR Sp1 binding site, were significantly more common in patients with HC, suggesting that these mutations may be indicative for the clinical diagnosis of HC and could influence the virulence of the virus.
Priftakis
P
P
Department of Oncology-Pathology, Cancer Centre Karolinska, Karolinska Institute, R 8:01, 17176 Stockholm, Sweden. peter.priftakis@cck.ki.se
Bogdanovic
G
G
Kalantari
M
M
Dalianis
T
T
D001739:BK Virus / Q000235:genetics*; D001665:Binding Sites; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002213:Capsid / Q000235:genetics; D003556:Cystitis / Q000150:complications / Q000652:urine / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D005814:Genes, Viral; D006417:Hematuria / Q000150:complications; D006470:Hemorrhage / Q000150:complications / Q000628:therapy; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications / Q000652:urine / Q000821:virology*; D017354:Point Mutation; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014412:Tumor Virus Infections / Q000150:complications / Q000652:urine / Q000821:virology*
D004279:DNA, Viral; D016329:Sp1 Transcription Factor