Characteristics of polyomavirus BK (BKPyV) infection in primary human urothelial cells

Characteristics of polyomavirus BK (BKPyV) infection in primary human urothelial cells
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DOI:
10.1016/j.virol.2013.01.024
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发表时间:
2013-05-25
期刊:
影响因子:
3.7
通讯作者:
Rinaldo, Christine Hanssen
Rinaldo, Christine Hanssen
中科院分区:
医学3区
文献类型:
--
作者:
Li, Ruomei;Sharma, Biswa Nath;Rinaldo, Christine Hanssen

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尿路上皮细胞中高水平的多瘤病毒BK(BKPyV)复制是多瘤病毒相关出血性膀胱炎(PyVHC)的标志,这是一种影响骨髓移植受者的疼痛状况。在肾移植受者中,肾小管上皮细胞中的复制与明显的疾病相关,而高水平的尿路上皮复制在临床上是沉默的。我们表征了BKPyV在原代人尿路上皮细胞(HUCs)中的复制,并将其与在肾小管上皮细胞(RPTEC)中的复制进行比较。HUCs很容易感染,表现为T抗原、VP 1 -3和未知蛋白的表达,以及核内病毒粒子的产生。与RPTEC相比,子代释放延迟>= 24 h并减少。BKPyV感染的HUCs像“诱饵细胞”一样聚集,并在没有坏死的情况下分离,如延迟的细胞角蛋白-18释放、实时活力监测和成像所示。数据显示,HUCs和RPTEC的BKV感染显著不同,并支持PyVHC发病机制不仅仅是由于BKPyV复制,而且可能需要尿毒性和免疫辅助因子的观点。(C)2013 Elsevier Inc. All rights reserved.
High-level polyomavirus BK (BKPyV) replication in urothelial cells is a hallmark of polyomavirus-associated hemorrhagic cystitis (PyVHC), a painful condition affecting bone marrow transplant recipients. In kidney transplant recipients, replication in tubular epithelial cells is associated with overt disease whereas high-level urothelial replication is clinically silent. We characterized BKPyV replication in primary human urothelial cells (HUCs) and compared it to replication in renal tubular epithelial cells (RPTECs). HUCs were easily infected, as shown by expression of T-antigens, VP1-3, and agnoprotein, and intranuclear virion production. Compared to RPTECs, progeny release was delayed by >= 24 h and reduced. BKPyV-infected HUCs rounded up like "decoy cells" and detached without necrosis as shown by delayed cytokeratin-18 release, real-time viability monitoring and imaging. The data show that BKV infection of HUCs and RPTECs is significantly different and support the notion that PyVHC pathogenesis is not solely due to BKPyV replication, but likely requires urotoxic and immunological cofactors. (C) 2013 Elsevier Inc. All rights reserved.