Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers
Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers
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DOI：
10.1016/j.virol.2007.10.016
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发表时间：
2008-03-01
期刊：
影响因子：
3.7
通讯作者：
Kunz, Stefan
中科院分区：
文献类型：
--
作者：
Lee, Andrew M.;Rojek, Jillian M.;Kunz, Stefan
原型沙粒病毒淋巴细胞性脉络丛脑膜炎病毒（LCMV）为研究沙粒病毒的基本病毒学和发病机制提供了一个强有力的实验模型。在本研究中，我们使用LCMV模型来评估磷硫寡核苷酸对沙粒病毒的抗病毒潜力。我们的研究结果表明，两亲性DNA聚合物（APs）是一系列IC50在低纳摩尔范围内的LCMV分离株感染的有效抑制剂。APs靶向LCMV的表面糖蛋白（GP），阻断病毒进入和病毒的细胞-细胞繁殖，而不影响感染细胞复制或释放子代病毒的后续步骤。ap的抗病毒作用依赖于序列，但主要依赖于它们的大小和疏水性。从机制上讲，我们提供的证据表明，APs破坏LCMVGP与其细胞受体α -歧化聚糖之间的相互作用。LCMV暴露于APs不会影响GP病毒粒子突刺的稳定性，也不会影响中和抗体表位的构象，这表明病毒GP的构象和/或构象动力学发生了相当微妙的变化。(C) 2007爱思唯尔公司版权所有。
The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) represents a powerful experimental model for the study of the basic virology and pathogenesis of arenaviruses. In the present study, we used the LCMV model to evaluate the anti-viral potential of phosphorothioate oligonucleotides against arenaviruses. Our findings indicate that amphipathic DNA polymers (APs) are potent inhibitors of infection with a series of LCMV isolates with IC50 in the low nanomolar range. APs target the surface glycoprotein (GP) of LCMV and block viral entry and cell-cell propagation of the virus, without affecting later steps in replication or release of progeny virus from infected cells. The anti-viral action of APs is sequence-in dependent but is critically dependent on their size and hydrophobicity. Mechanistically, we provide evidence that APs disrupt the interaction between LCMVGP and its cellular receptor, alpha-dystroglycan. Exposure of LCMV to APs does not affect the stability of the GP virion spike and has no effect on the conformation of a neutralizing antibody epitope, suggesting rather subtle changes in the conformation and/or conformational dynamics of the viral GP. (C) 2007 Elsevier Inc. All rights reserved.