Mutations in the external loops of BK virus VP1 and urine viral load in renal transplant recipients.
Polyomavirus-associated nephropathy (PVAN) is a major complication that occurs after renal transplantation and is induced by reactivation of the human polyomavirus BK (BKV). The structure of the viral capsid protein 1 (VP1) is characterized by the presence of external loops, BC, DE, EF, GH, and HI, which are involved in receptor binding. The pathogenesis of PVAN is not well understood, but viral risk factors are thought to play a crucial role in the onset of this pathology. In an attempt to better understand PVAN pathogenesis, the BKV-VP1 coding region was amplified, cloned, and sequenced from the urine of kidney transplant recipients who did, and did not, develop the pathology. Urine viral loads were determined by using real time quantitative PCR (Q-PCR). Amino acid substitutions were detected in 6/8 patients, and 6/7 controls. The BC and EF loop regions were most frequently affected by mutations, while no mutations were found within the GH and HI loops of both patients and controls. Some mutations, that were exclusively detected in the urine of PVAN patients, overlapped with previously reported mutations, although a correlation between changes in amino acids and the development of PVAN was not found. Urine viral loads were higher than that of the proposed cut-off loads for identification of patients that are at a high risk of developing PVAN (10(7) copies/ml), both in the PVAN and control groups, thus confirming that urine viral load is not a useful predictive marker for the development of PVAN.
Department of Public Health-Microbiology-Virology, University of Milan, Milan, Italy.
Sara
S
Tremolada
Serena
S
Delbue
Lorenzo
L
Castagnoli
Sara
S
Allegrini
Umberto
U
Miglio
Renzo
R
Boldorini
Francesca
F
Elia
Jennifer
J
Gordon
Pasquale
P
Ferrante
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001739:BK Virus / Q000235:genetics* / Q000302:isolation & purification; D016022:Case-Control Studies; D016384:Consensus Sequence; D003710:Demography; D005260:Female; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D027601:Polyomavirus Infections / Q000652:urine* / Q000821:virology*; D017433:Protein Structure, Secondary; D019562:Viral Load; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*
D014764:Viral Proteins