BK Polyomavirus Genetic Diversity and Evolution in Kidney Transplant Recipients With Viral Nephropathy According to...

Among kidney transplant recipients (KTRs) with BK polyomavirus (BKPyV)-associated nephropathy (BKPyVN), the dynamics of BKPyV replication are not well established. We aim to investigate BKPyV genetic diversity and evolution following kidney transplant.

We retrospectively analyzed 32 KTRs with a biopsy-proven diagnosis of BKPyVN. Stored plasma and kidney biopsies were tested for BKPyV viral load, and BKPyV whole genome sequencing was performed on BKPyV-positive samples.

A total of 104 samples positive for BKPyV DNA detection were sequenced, among which 83 were included in the analysis. BKPyV-I was the most frequent genotype detected, followed by BKPyV-IVc2 and BKPyV-II. At BKPyVN diagnosis (median [IQR], 12 [8-17] months posttransplant), whole genome sequencing identified the same BKPyV subtype in the plasma and kidney biopsy for all patients but one. Alignment of BKPyV consensus sequences between the 2 compartments at the time of BKPyVN showed similarity >99% but identified single-nucleotide polymorphisms in 13 of 23 cases, including 25% APOBEC-associated mutations. Among the 16 KTRs with ≥2 consecutive BKPyV-positive samples available for analysis, consensus sequence showed a different BKPyV subtype in pre-BKPyVN kidney biopsies as compared with BKPyVN in 9 patients. Before BKPyVN diagnosis, minority variants on the VP1 sequence were identified in 10 of 11 kidney biopsy samples and 5 of 10 plasma samples.

Among KTRs with BKPyVN, we show that BKPyV viral populations change over time, with the coexistence of several viral populations in early samples as compared with BKPyVN, as a result of APOBEC-mediated editing and replication-driven diversification within the kidney allograft.