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

Abstract

BK polyomavirus (BKPyV) is a human DNA virus that resides latent in the host’s renal tissue. Reactivation occurs occasionally and in case of kidney transplantation, it can lead to polyomavirus-associated nephropathy (PVAN). Due to the lack of specific antivirals for BKPyV and despite the risk of allograft rejection, reduction of immunosuppression remains the main approach for treating PVAN. Current data suggests that mutations can accumulate over time in the major capsid protein VP1 and can lead to neutralization escape in kidney transplant recipients. Herein, we show that mutations occur throughout the entire BKPyV genome, including in VP1. Changes were identified by per-patient comparison of viral genome sequences obtained in samples from 32 kidney recipients with persistent viremia collected at different post-transplant time-points. Amino acid changes were observed in both earlier and later post-transplant samples, although some of them were only found in later samples. Changes in VP1 mainly consisted in the introduction of a new amino acid. A switch back to the conservative amino acid was also observed. This should be considered in future approaches for treating BKPyV infection in kidney transplant recipients.

Acute Kidney Injury and BK Polyomavirus in Urine Sediment Cells

“…This part of the BKV genome does not appear to be as polymorphic, and PCR will not miss rare genotypes. However, it has recently been shown that this protein can also undergo mutations in rare cases [30]. Despite this potential ambiguity of their test, previous authors have already provided proof of concept by demonstrating high test specificity and sensitivity of over 90% for the diagnostics of BKPyVAN in their test setup [16].…”

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 and the lack of specific antivirals for the BK virus. 75 Solomyannyi et al synthesized imidazo[1,2- c ]pyrimidine derivatives and evaluated them against BK polyomavirus for their anticancer potential. Compound 33 , 6-benzyl-8-(methylsulfonyl)-2,6-dihydroimidazo[1,2- c ]pyrimidin-5(3 H )-one, was found to be the most potent molecule of the series with an EC 50 of 0.66 μM [Table 9].…”

Prevalence of IgG antibodies against Malawi polyomavirus in patients with autoimmune diseases and lymphoproliferative disorders subjected to bone marrow transplantation

“…It has been reported that HPyVs may infect asymptomatic subjects during early childhood, followed by a latency stage. In a peculiar condition of the host, such as immunosuppressive status, HPyVs may reactivate ( 3 , 9 , 10 ). HPyV6, HPyV7, and TSPyV have been associated with rare skin lesions in immunosuppressed patients ( 11 ).…”