Laboratory of Virology and Chemotherapy, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000, Leuven, Belgium.
Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000, Leuven, Belgium.
Sci Rep. 2023 Aug 19;13(1):13534. doi: 10.1038/s41598-023-40714-4.
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.
BK 多瘤病毒（BKPyV）是一种潜伏在宿主肾脏组织中的人类 DNA 病毒。偶尔会发生病毒激活，在肾移植的情况下，可能导致多瘤病毒相关性肾病（PVAN）。由于缺乏针对 BKPyV 的特定抗病毒药物，并且存在移植物排斥的风险，因此降低免疫抑制仍然是治疗 PVAN 的主要方法。目前的数据表明，VP1 主要衣壳蛋白中的突变可以随着时间的推移而积累，并导致肾移植受者的中和逃逸。在此，我们展示了突变发生在整个 BKPyV 基因组中，包括 VP1 区域。通过对 32 名持续性病毒血症的肾移植受者在不同移植后时间点采集的样本中的病毒基因组序列进行逐个患者比较，确定了突变的存在。在早期和晚期移植后样本中均观察到氨基酸变化，但其中一些仅在晚期样本中发现。VP1 中的变化主要包括引入新的氨基酸。还观察到回落到保守氨基酸的突变。在未来治疗肾移植受者 BKPyV 感染的方法中，应考虑到这一点。
