Hannover Medical School, Institute of Virology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.
Hannover Medical School, Department of Nephrology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
J Clin Virol. 2014 Feb;59(2):120-5. doi: 10.1016/j.jcv.2013.11.009. Epub 2013 Dec 1.
BK virus associated nephropathy (BKVN) leads to renal allograft dysfunction and loss. However, it is still unclear whether BKV replication in the transplant recipient is a result of reactivation in the recipient's native kidneys or whether BKV originates from the donor kidney.
Urine of 249 donor/recipient pairs was investigated for the presence of BKV-DNA by qPCR before living transplantation (Tx) and consecutively after Tx. In BKV positive samples, the VP1 typing region (TR) and, in case of the presence of sufficient amount of DNA, the complete VP1 gene, the NCCR and a fragment of the Large T-antigen were sequenced and compared between donors and corresponding recipients before and after Tx.
In 20 pairs, sequencing of the BKV TR succeeded in donors and corresponding recipients after Tx. The derived sequences were completely identical in donor and post-Tx recipient samples. For comparison, identical TR sequences were detected in only 24% of 1068 randomly assembled pairs. This difference was statistically highly significant (p<0.0001, Fisher's exact test). Furthermore, all VP1, Large T-antigen and NCCR BKV sequences were also identical between donors and corresponding post-Tx recipients. In two of the 20 donor/recipient pairs, VP1 TR sequencing was also successful from the recipient before Tx. In both cases the sequence differed from the sequence detected in donor and recipient after Tx giving further evidence that recipient BKV was replaced by donor BKV after Tx.
Our study for the first time provides evidence of BKV donor origin in renal transplant recipients.
BK 病毒相关性肾病(BKVN)可导致肾移植功能障碍和丧失。然而,目前尚不清楚移植受者中的 BKV 复制是受者自身肾脏内的再激活所致,还是源自供体肾脏。
在活体移植(Tx)前和 Tx 后连续采集 249 对供体/受者的尿液,通过 qPCR 检测 BKV-DNA 的存在。在 BKV 阳性样本中,对 VP1 型区(TR)进行测序,并在有足够 DNA 量的情况下,对完整的 VP1 基因、NCCR 和大 T 抗原的一个片段进行测序,并比较 Tx 前后供体和相应受者之间的序列。
在 20 对中,成功对 Tx 后供体和相应受者的 BKV TR 进行了测序。衍生序列在供体和 Tx 后受者样本中完全相同。相比之下,在 1068 对随机组装的样本中,只有 24%检测到相同的 TR 序列。这一差异具有统计学显著性(p<0.0001,Fisher 精确检验)。此外,供体和相应 Tx 后受者之间的所有 VP1、大 T 抗原和 NCCR BKV 序列也完全相同。在 20 对供体/受者对中的 2 对中,也成功对 Tx 前受者的 VP1 TR 进行了测序。在这两种情况下,序列与 Tx 后供体和受者检测到的序列不同,进一步证明 Tx 后受者的 BKV 被供体的 BKV 取代。
本研究首次提供了肾移植受者中 BKV 供体起源的证据。