BACKGROUND BKPyV is associated with polyomavirus-associated nephropathy (PVAN), a major cause of graft rejection in kidney transplant recipients (KTRs). Mutations occur in the transcriptional control region (TCR) of BKPyV, but whether they are required for the development of PVAN is not completely understood. To this end, we characterized BKPyV TCRs from KTRs to assess whether TCR mutations are associated with PVAN. STUDY DESIGN We analyzed urine and plasma samples of fifteen KTRs with biopsy-confirmed PVAN, presumptive PVAN, or probable PVAN in order to explore the contents of the BKPyV virome. BKPyV TCRs were amplified and deep sequenced to characterize the viral strains. Alterations in block structures and transcription factor binding sites were investigated. RESULTS The majority of sequences in both urine and plasma samples represented archetype BKPyV TCR. Minor populations harboring rearranged TCRs were detected in all patient groups. In one biopsy-confirmed PVAN patient rearranged TCRs predominated, and in another patient half of all reads represented rearranged sequences. CONCLUSIONS Although archetype BKPyV predominated in most patients, highest proportions and highest numbers of rearranged strains were detected in association with PVAN. TCR mutations seem not necessary for the development of PVAN, but immunosuppression may allow increased viral replication giving rise to TCR variants with enhanced replication efficiency.

中文翻译：

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下一代测序显示出BK多瘤病毒明显的重排，有利于但不是多瘤病毒相关性肾病所必需的。

背景技术BKPyV与多瘤病毒相关性肾病（PVAN）相关，后者是肾移植受者（KTR）移植排斥的主要原因。突变发生在BKPyV的转录控制区（TCR）中，但尚未完全了解PVAN的发育是否需要突变。为此，我们从KTRs中鉴定了BKPyV TCRs，以评估TCR突变是否与PVAN相关。研究设计我们通过活检确认的PVAN，推定性PVAN或可能的PVAN分析了15个KTR的尿液和血浆样本，以研究BKPyV病毒体的含量。BKPyV TCRs被扩增并进行深度测序以表征病毒株。研究了嵌段结构和转录因子结合位点的变化。结果尿液和血浆样品中的大多数序列均代表原型BKPyV TCR。在所有患者组中均发现了携带重排TCR的少数人群。在一位活检证实的PVAN患者中，重排的TCR占主导地位，在另一位患者中，所有读数的一半代表重排的序列。结论尽管大多数患者中原型BKPyV占主导地位，但与PVAN相关的重排菌株的比例最高且数量最高。TCR突变对于PVAN的发展似乎不是必需的，但是免疫抑制可以使病毒复制增加，从而产生具有增强复制效率的TCR变异体。在另一位患者中，所有读数的一半代表重新排列的序列。结论尽管大多数患者中原型BKPyV占主导地位，但与PVAN相关的重排菌株的比例最高且数量最高。TCR突变对于PVAN的发展似乎不是必需的，但是免疫抑制可以使病毒复制增加，从而产生具有增强复制效率的TCR变异体。在另一位患者中，所有读数的一半代表重新排列的序列。结论尽管大多数患者中原型BKPyV占主导地位，但与PVAN相关的重排菌株的比例最高且数量最高。TCR突变对于PVAN的发展似乎不是必需的，但是免疫抑制可以使病毒复制增加，从而产生具有增强复制效率的TCR变异体。