Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation
Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation
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DOI：
10.1016/j.virol.2007.08.034
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发表时间：
2008-01-05
期刊：
影响因子：
3.7
通讯作者：
Sawa, Hirofumi
中科院分区：
文献类型：
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作者：
Orba, Yasuko;Sunden, Yuji;Sawa, Hirofumi
人类多瘤病毒JC病毒(JCV)利用细胞蛋白在宿主细胞核内复制和转录病毒。这些细胞蛋白是抗JCV药物的潜在靶点。在这项研究中，我们研究了药物周期蛋白依赖激酶(CDK)抑制剂R-rocovitine的抗病毒作用，它已被证明对其他病毒具有抗病毒活性。我们发现，在JCV感染的细胞系中，罗斯科维汀显著抑制JCV的病毒产生和细胞病变效应。罗索维汀减弱JCV晚期基因的转录活性，但不减弱早期基因的转录活性，并通过抑制病毒早期蛋白大T抗原的磷酸化来阻止病毒复制。这些数据表明，JCV需要CDK转录晚期基因并复制自己的DNA。罗可维汀在JCV感染的细胞中显示出抗病毒活性，这表明罗可维汀可能在治疗进行性多灶性白质脑病(PML)中具有治疗作用。(C)2007 Elsevier Inc.保留所有权利。
The human Polyomavirus JC virus (JCV) utilizes cellular proteins for viral replication and transcription in the host cell nucleus. These cellular proteins represent potential targets for antiviral drugs against the JCV. In this study, we examined the antiviral effects of the pharmacological cyclin-dependent kinase (cdk) inhibitor R-Roscovitine, which has been shown to have antiviral activity against other viruses. We found that Roscovitine significantly inhibited the viral production and cytopathic effects of the JCV in a JCV-infected cell line. Roscovitine attenuated the transcriptional activity of JCV late genes, but not early genes, and also prevented viral replication via inhibiting phosphorylation of the viral early protein, large T antigen. These data suggest that the JCV requires cdks to transcribe late genes and to replicate its own DNA. That Roscovitine exhibited antiviral activity in JCV-infected cells suggests that Roscovitine might have therapeutic utility in the treatment of progressive multifocal leukoencephalopathy (PML). (c) 2007 Elsevier Inc. All rights reserved.