Proteasome inhibitor MG132 blocks viral DNA replication and assembly of human cytomegalovirus
Proteasome inhibitor MG132 blocks viral DNA replication and assembly of human cytomegalovirus
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DOI：
10.1016/j.febslet.2008.01.040
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发表时间：
2008-03-05
期刊：
影响因子：
3.5
通讯作者：
Bogner, Elke
中科院分区：
文献类型：
--
作者：
Kaspari, Marion;Tavalai, Nina;Bogner, Elke
这项研究提供的证据表明，蛋白酶体的活性是需要在多个步骤在人类巨细胞病毒复制。电子显微镜显示，没有病毒颗粒组装蛋白酶体抑制剂MG132的存在下。使用MG132的免疫荧光和Western印迹分析表明，立即早期基因表达在低MOI下被抑制，但在高MOI下不被抑制。与此相反，晚期蛋白的表达被完全阻断独立于MOI。此外，脉冲场凝胶电泳证明MG 132干扰HCMV DNA的切割。溴去氧尿苷掺入研究表明，在MG 132的存在下，病毒DNA的从头合成减少。此外，与先前的假设相反，我们证明了ND10组分PML和hDaxx或NF κ B活化都不代表MG 132的靶点。(C)2008年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
This study provides evidence that proteasomal activity is required at multiple steps in human cytomegalovirus replication. Electron microscopy revealed that no viral particles were assembled in the presence of proteasome inhibitor MG132. Immunofluorescence and Western blot analyses using MG132 demonstrated that immediate early gene expression was suppressed at low but not high MOI. In contrast, expression of late proteins was completely blocked independent of MOI. Additionally, pulsed-field gel electrophoresis demonstrated that MG132 interferes with cleavage of HCMV DNA. Bromodeoxyuridine incorporation studies showed that de novo viral DNA synthesis is reduced in the presence of MG132. Furthermore, in contrast to previous hypotheses we demonstrated that neither the ND10 components PML and hDaxx nor NF kappa B activation represent the target for MG132. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.