Do BKPyV genomic features underlie clinical divergence between kidney and hematopoietic transplant recipients?

BK polyomavirus (BKPyV) persists in the renourinary tract of most adults and can replicate under immunosuppression. In kidney transplant recipients (KTR), it may cause BKPyV-associated nephropathy (BKPyVAN), while in hematopoietic stem cell transplant recipients (HSCT), it is more often linked to hemorrhagic cystitis (HC). These clinical differences are generally attributed to the type of graft and immunosuppressive regimen. However, viral factors such as genotype or mutations might also influence tissue tropism and pathogenesis. This study aimed to compare the virological features of BKPyV between KTR and HSCT recipients and to explore possible associations with clinical manifestations. This retrospective study included 101 transplanted patients (66 KTR, 35 HSCT) at Amiens-Picardie University Hospital (France) between 2019 and 2023, with at least one episode of BKPyV DNAuria during post-allograft follow-up. Viral genotyping was performed by Sanger sequencing, while NGS (Next-generation Sequencing) provided complete coding genome sequences for 51 patients. Genotype distribution was similar in both groups, with Ib2 as the most frequent subtype. No genotype or mutation was associated with a specific graft type or complication, except for the small t antigen gene, which appeared to be more frequently mutated in KTRs. Viral replication occurred earlier and at higher levels in HSCT patients (mean peak DNAuria: 9.3 log10 vs 7.4 log10 copies/mL in KTR; p < 0.0001). In KTRs, patients with presumptive BKPyVAN were significantly older than those with asymptomatic replication. These findings suggest that viral genetic determinants play a lesser role in BKPyV replication and its clinical consequences compared to host-related factors.