Unique BK virus non-coding control region (NCCR) variants in hematopoietic stem cell transplant recipients with and without hemorrhagic cystitis.
Hematopoietic stem cell transplant recipients frequently develop BK virus (BKV)-associated hemorrhagic cystitis, which coincides with BK viruria. However, the precise role of BKV in the etiology of hemorrhagic cystitis in hematopoietic stem cell transplant recipients remains unclear, since approximately 50% of all such adult transplant recipients excrete BKV, yet do not develop this clinical condition. In the present study, BKV were analyzed to determine if mutations in the non-coding control region (NCCR), and specific BKV sub-types defined by sequence analysis of major capsid protein VP1, were associated with development of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. The regions encoding VP1 and NCCRs of BKV in urine samples collected from 15 hematopoietic stem cell transplant recipients with hemorrhagic cystitis and 20 without this illness were amplified and sequenced. Sequence variations in the NCCRs of BKV were identified in urine samples from those with and without hemorrhagic cystitis. Furthermore, five unique sequence variations within transcription factor binding sites in the canonical NCCR, O-P-Q-R-S, were identified, representing new BKV variants from a population of cloned quasi-species obtained from patients with and without hemorrhagic cystitis. Thirty-five BKV VP1 sequences were analyzed by phylogenetic analysis but no specific BKV sub-type was associated with hemorrhagic cystitis. Five previously unrecognized naturally occurring variants of the BKV are described which involve amplifications, deletions, and rearrangements of the archetypal BKV NCCRs in individuals with and without hemorrhagic cystitis. Architectural rearrangements in the NCCRs of BKV did not appear to be a prerequisite for development of hemorrhagic cystitis in hematopoietic stem cell transplant recipients.
Department of Clinical Microbiology, Trinity Centre for Health Sciences, University of Dublin, Trinity College, St. James's Hospital, Dublin, Ireland.
Michael J
MJ
Carr
Grace P
GP
McCormack
Ken J
KJ
Mutton
Brendan
B
Crowley
D000293:Adolescent; D000328:Adult; D001739:BK Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics*; D003556:Cystitis / Q000150:complications / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004742:Enhancer Elements, Genetic; D005260:Female; D014644:Genetic Variation; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006470:Hemorrhage / Q000150:complications / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D027601:Polyomavirus Infections / Q000150:complications / Q000821:virology*; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology*; D014556:Urine / Q000821:virology
D036022:Capsid Proteins; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus