Mutations in the BC-loop of the BKV VP1 region do not influence viral load in renal transplant patients.
The reactivation and replication of the BK polyomavirus (BKV) leading to BKV-associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I-IV) based on genotype variations within the VP1-coding region. The type-specific amino acid differences cluster within the BC-loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC-loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC-loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC-loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC-loops.
Krautkrämer
Ellen
E
Department of Nephrology, University of Heidelberg, Heidelberg, Germany. ellen_krautkraemer@med.uni-heidelberg.de
Klein
Theresa M
TM
Sommerer
C
C
Schnitzler
Paul
P
Zeier
Martin
M
D001739:BK Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D036022:Capsid Proteins / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D027601:Polyomavirus Infections / Q000821:virology*; D017422:Sequence Analysis, DNA; D014556:Urine / Q000821:virology; D019562:Viral Load; D014779:Virus Replication
D036022:Capsid Proteins; D004279:DNA, Viral