The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus.
The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus.
复制标题
DOI：
10.3390/v8100295
复制
发表时间：
2016-10-24
期刊：
影响因子：
--
通讯作者：
Tortorella D
中科院分区：
文献类型：
--
作者：
Cohen T;Schwarz TM;Vigant F;Gardner TJ;Hernandez RE;Lee B;Tortorella D
人巨细胞病毒是一种普遍存在的β-疱疹病毒，其通过与细胞表面受体的初始结合，随后在细胞膜或内吞囊泡处发生融合事件来感染许多不同的细胞类型。最近的一项高通量筛选，以确定化合物，阻断病毒基因表达前的一个步骤，确定podofilox作为一个有效的和无毒的抑制剂。加入时间研究结合定量PCR分析表明，podofilox限制了病毒进入细胞表面的早期步骤。Podofilox还能够显著降低单纯疱疹1型（一种α-疱疹病毒，其进入过程与CMV非常相似）的感染。在融合样纽卡斯尔病毒、仙台病毒和甲型流感病毒或通过内吞作用进入的病毒（如水泡性口炎病毒和临床样CMV毒株）之前，Podofilox通过单步结合过程降低了对病毒感染的最大平台期抑制。这些结果表明，微管似乎参与了病毒进入的后结合步骤，包括前和后穿透事件。调节质膜是促进疱疹病毒进入所必需的，并且与秋水仙碱或诺考达唑不同，podofilox能够优先靶向质膜上的微管网络。
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface. Podofilox was also able to drastically reduce infection by herpes simplex 1, an α-herpesvirus with a very similar entry process to CMV. Podofilox caused a reduced maximal plateau inhibition of infection by viruses with single step binding processes prior to fusion-like Newcastle disease virus, Sendai virus, and influenza A virus or viruses that enter via endocytosis like vesicular stomatitis virus and a clinical-like strain of CMV. These results indicate that microtubules appear to be participating in the post-binding step of virus entry including the pre- and post-penetration events. Modulation of the plasma membrane is required to promote virus entry for herpesviruses, and that podofilox, unlike colchicine or nocodazole, is able to preferentially target microtubule networks at the plasma membrane.
登录
查看更多内容
影响因子：
7.6
作者：
Gardner, Thomas J.;Cohen, Tobias;Redmann, Veronika;Lau, Zerlina;Felsenfeld, Dan;Tortorella, Domenico
通讯作者：
Tortorella, Domenico
影响因子：
3.8
作者：
Cantin, Celia;Holguera, Javier;Munoz-Barroso, Isabel
通讯作者：
Munoz-Barroso, Isabel
影响因子：
4
作者：
Hoffmann, Christine;Berking, Anne;Hauck, Christof R.
通讯作者：
Hauck, Christof R.
影响因子：
8.9
作者：
Delgado, Juan F.;Garcia Reyne, Ana;Lumbreras, Carlos
通讯作者：
Lumbreras, Carlos
DOI：
10.1073/pnas.0406821101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Feire, AL;Koss, H;Compton, T
通讯作者：
Compton, T