Roy Sanjeet, Mieczkowski Piotr A, Weida Carol, Huo Jeffrey, Roehrs Philip, Singh Harsharan K, Nickeleit Volker
Division of Nephropathology, The University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Department of Genetics, The University of North Carolina, Chapel Hill, NC, USA.
Transpl Infect Dis. 2020 Apr;22(2):e13269. doi: 10.1111/tid.13269. Epub 2020 Mar 14.
BK polyomavirus (BKPyV) infections with multi-organ involvement are rare. Here, we report for the first time whole genome sequencing data from a patient with systemic BKPyV disease. She presented post stem cell transplantation with graft-vs-host disease, suffered from profound immunosuppression, and developed fatal BKPyV disease of kidneys, lungs, and pancreas. The lytic infection was caused by an episomal BKPyV-Ib strain with canonical structural and receptor encoding gene sequences. However, DNA from all infected tissue sites showed diverse BKPyV-NCCR rearrangements (rr-NCCR) involving the P, Q, and R domains, while largely sparing O and S, carrying initiation sites for early and late BKPyV gene transcripts crucial for viral replication and assembly. Common to all rr-NCCR variants was a break point in Q (position 17-27) that can form the nidus for double DNA strand break formation and gene rearrangements. Metastatic clonal BKPyV spread from kidneys to other organs was not detected. We hypothesize that lack of immune surveillance and a specific NCCR break point promote profound gene rearrangements of NCCR-P, Q, and R with alterations of regulatory feedback loops. As a result, viral replication and pathogenicity are enhanced leading to severe, often fatal systemic disease not caused by the common archetypical BKPyV strains.
BK多瘤病毒（BKPyV）感染累及多器官的情况较为罕见。在此，我们首次报告了一名全身性BKPyV疾病患者的全基因组测序数据。她在干细胞移植后出现移植物抗宿主病，处于深度免疫抑制状态，并发展为累及肾脏、肺和胰腺的致命性BKPyV疾病。溶细胞性感染由具有典型结构和受体编码基因序列的游离型BKPyV-Ib毒株引起。然而，所有感染组织部位的DNA均显示出涉及P、Q和R结构域的多样的BKPyV非编码控制区重排（rr-NCCR），而O和S结构域基本未受影响，这些结构域携带了对病毒复制和组装至关重要的早期和晚期BKPyV基因转录起始位点。所有rr-NCCR变体的共同之处在于Q结构域（第17 - 27位）存在一个断点，该断点可形成双链DNA断裂形成和基因重排的核心位点。未检测到BKPyV从肾脏转移至其他器官的克隆性播散。我们推测，免疫监视的缺失和特定的非编码控制区断点会促进NCCR的P、Q和R结构域发生深度基因重排，并改变调节反馈环。结果，病毒复制和致病性增强，导致严重的、通常致命的全身性疾病，而这并非由常见的原型BKPyV毒株引起。
