The VP1 subunit of JC polyomavirus recapitulates early events in viral trafficking and is a novel tool to study polyomavirus entry

The VP1 subunit of JC polyomavirus recapitulates early events in viral trafficking and is a novel tool to study polyomavirus entry
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DOI:
10.1016/j.virol.2012.03.014
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发表时间:
2012-06-20
期刊:
影响因子:
3.7
通讯作者:
Atwood, Walter J.
Atwood, Walter J.
中科院分区:
医学3区
文献类型:
--
作者:
Nelson, Christian D. S.;Derdowski, Aaron;Atwood, Walter J.

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JC多瘤病毒(JC polyomavirus,JCV)是一种重要的人类病原体,可引起致死性脱髓鞘疾病进行性多灶性白质脑病(progressive multifocal leukoencephalopathy,PML)。在这项研究中,我们进一步描绘了人类神经胶质细胞中JCV进入的早期事件,并证明了病毒衣壳的五聚体亚基能够重演病毒运输的早期事件。我们表明,JCV交通内质网(ER)的6小时后感染,和VP1五聚体到达ER具有相似的动力学。此外,这种JCV定位于ER对于感染是关键的,因为用阻止ER运输、ER功能或ER质量控制的试剂处理细胞会降低JCV的感染性。这些五聚体代表了研究多瘤病毒进入的新工具,并且在研究最近鉴定的难以繁殖的多瘤病毒中将特别有用。(C)2012 Elsevier Inc. All rights reserved.
JC polyomavirus (JCV) is an important human pathogen that causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In this study we further delineate the early events of JCV entry in human glial cells and demonstrate that a pentameric subunit of the viral capsid is able to recapitulate early events in viral trafficking. We show that JCV traffics to the endoplasmic reticulum (ER) by 6 h post infection, and that VP1 pentamers arrive at the ER with similar kinetics. Further, this JCV localization to the ER is critical for infection, as treatment of cells with agents that prevent ER trafficking, ER function, or ER quality control reduce JCV infectivity. These pentamers represent a new tool to study polyomavirus entry, and will be particularly useful in studying recently identified polyomaviruses that are difficult to propagate. (C) 2012 Elsevier Inc. All rights reserved.