Human polyoma JC virus minor capsid proteins, VP2 and VP3, enhance large T antigen binding to the origin of viral DNA replication: evidence for their involvement in regulation of the viral DNA replication.
Human polyoma JC virus minor capsid proteins, VP2 and VP3, enhance large T antigen binding to the origin of viral DNA replication: evidence for their involvement in regulation of the viral DNA replication.
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DOI：
10.1016/j.virol.2013.10.031
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发表时间：
2014-01-20
期刊：
影响因子：
3.7
通讯作者：
Safak, Mahmut
中科院分区：
文献类型：
--
作者：
Saribas, A. Sami;Mun, Sarah;Johnson, Jaslyn;El-Hajmoussa, Mohammad;White, Martyn K.;Safak, Mahmut
关键词：
JC病毒（JCV）可溶解性感染免疫功能低下患者中枢神经系统中的少突胶质细胞，并导致脱髓鞘疾病，即进行性多灶性白质脑病。JCV在细胞核中复制并组装成感染性病毒体。然而，了解其病毒粒子生物发生的分子机制仍然是难以捉摸的。在这份报告中，我们试图通过研究大T抗原（LT-Ag），热休克蛋白70和次要衣壳蛋白，VP 2/VP 3之间的分子相互作用来阐明这一过程。我们证明了Hsp 70与VP 2/VP 3和LT-Ag相互作用，并在感染细胞的细胞核中大量积累。我们还发现，VP 2/VP 3通过其DNA结合结构域与LT-Ag缔合，导致LT-Ag DNA与Ori的结合增强并诱导病毒DNA复制。总而言之，我们的结果表明VP 2/VP 3和Hsp 70积极参与JCV DNA复制，并可能在病毒DNA复制与病毒粒子衣壳化的偶联中发挥关键作用。
JC virus (JCV) lytically infects the oligodendrocytes in the central nervous system in a subset of immunocompromized patients and causes the demyelinating disease, progressive multifocal leukoencephalopathy. JCV replicates and assembles into infectious virions in the nucleus. However, understanding the molecular mechanisms of its virion biogenesis remains elusive. In this report, we have attempted to shed more light on this process by investigating molecular interactions between large T antigen (LT-Ag), Hsp70 and minor capsid proteins, VP2/VP3. We demonstrated that Hsp70 interacts with VP2/VP3 and LT-Ag; and accumulates heavily in the nucleus of the infected cells. We also showed that VP2/VP3 associates with LT-Ag through their DNA binding domains resulting in enhancement in LT-Ag DNA binding to Ori and induction in viral DNA replication. Altogether, our results suggest that VP2/VP3 and Hsp70 actively participate in JCV DNA replication and may play critical roles in coupling of viral DNA replication to virion encapsidation.
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影响因子：
10.5
作者：
Campbell, KS;Mullane, KP;DeCaprio, JA
通讯作者：
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DOI：
10.1007/bf00446910
发表时间：
1977-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
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作者：
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