Polyomavirus BK Genome Comparison Shows High Genetic Diversity in Kidney Transplant Recipients Three Months after Transplantation

Abstract

BK polyomavirus (BKPyV) is a human DNA virus generally divided into twelve subgroups based on the genetic diversity of Viral Protein 1 (VP1). BKPyV can cause polyomavirus-associated nephropathy (PVAN) after kidney transplantation. Detection of BKPyV DNA in blood (viremia) is a source of concern and increase in plasma viral load is associated with a higher risk of developing PVAN. In this work, we looked for possible associations of specific BKPyV genetic features with higher plasma viral load in kidney transplant patients. We analyzed BKPyV complete genome in three-month samples from kidney recipients who developed viremia during their follow-up period. BKPyV sequences were obtained by next-generation sequencing and were de novo assembled using the new BKAnaLite pipeline. Based on the data from 72 patients, we identified 24 viral groups with unique amino acid sequences: three in the VP1 subgroup IVc2, six in Ib1, ten in Ib2, one in Ia, and four in II. In none of the groups did the mean plasma viral load reach a statistically significant difference from the overall mean observed at three months after transplantation. Further investigation is needed to better understand the link between the newly described BKPyV genetic variants and pathogenicity in kidney transplant recipients.

Time-dependent variations in BK polyomavirus genome from kidney transplant recipients with persistent viremia

“…We first characterized viral sequences based on the VP1 gene (BKPyV subtype/subgroup), the NCCR and the entire protein-coding region. After, we compared viral sequences with those previously obtained in three-month post-transplant samples from the same patients 35 . For BKPyV, we had 30 (whole or partial) genome consensus sequences obtained in urine samples and 21 obtained in plasma samples available for comparison.…”

“…The study enrolled 85 kidney transplant recipients with viremia (BKPyV/JCPyV quantitative PCR; quantification range 2.7–7.7 log10 copies/mL) from our previous retrospective cohort study 35 . Samples were taken from patients with at least one qPCR positive plasma sample (≥ 2.7 log 10 copies/mL) detected at 250 days or more after the patient’s first positive plasma event (48 patients).…”

“…BKPyV complete genome consensus sequences were generated using the recently developed BKAnaLite bioinformatics pipeline 35 and submitted into GenBank under accession numbers OQ230834–OQ230874 (n = 41). The JCPyV genome sequence was obtained using the CLC Genomics Workbench v12.0.3 software package (Qiagen Benelux, The Netherlands).…”

“…In the present study, we aim at better understanding changes over time in the BKPyV genome in kidney transplant recipients. Building upon our previous analysis of BKPyV (and JCPyV) genome in three-month post-transplant samples from kidney recipients with viremia 35 , we characterized viral genomes from patients with persisting viremia over a longer period. We compared the viral genomes pairs of each patient and identified the changes that occurred over time, also in relation to cidofovir.…”

Imidazopyrimidine: from a relatively exotic scaffold to an evolving structural motif in drug discovery

“…Reducing immunosuppression is still the primary treatment strategy for PVAN, despite the danger of allograft rejection the lack of specific antivirals for the BK virus. 75 9]. 76 6.…”