一种可中和1型人类免疫缺陷病毒R5毒株的适配体可阻断gp120与CCR5的相互作用。
An aptamer that neutralizes R5 strains of human immunodeficiency virus type 1 blocks gp120-CCR5 interaction.
作者信息
Dey Antu K, Khati Makobetsa, Tang Min, Wyatt Richard, Lea Susan M, James William
机构信息
Laboratory of Molecular Biophysics, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
出版信息
J Virol. 2005 Nov;79(21):13806-10. doi: 10.1128/JVI.79.21.13806-13810.2005.
Abstract
We recently described the isolation and structural characterization of 2'-fluoropyrimidine-substituted RNA aptamers that bind to gp120 of R5 strains of human immunodeficiency virus type 1 and thereby potently neutralize the infectivity of phylogenetically diverse R5 strains. Here we investigate the physical basis of their antiviral action. We show that both N-linked oligosaccharides and the variable loops V1/V2 and V3 are not required for binding of one aptamer, B40, to gp120. Using surface plasmon resonance binding analyses, we show that the aptamer binds to the CCR5-binding site on gp120 in a relatively CD4-independent manner, providing a mechanistic explanation for its neutralizing potency.
摘要
我们最近描述了2'-氟嘧啶取代的RNA适配体的分离和结构表征，这些适配体与人类免疫缺陷病毒1型R5株的gp120结合，从而有效地中和系统发育上不同的R5株的感染性。在此，我们研究了它们抗病毒作用的物理基础。我们表明，对于一种适配体B40与gp120的结合，N-连接寡糖以及可变环V1/V2和V3并非必需。通过表面等离子体共振结合分析，我们表明该适配体以相对不依赖CD4的方式与gp120上的CCR5结合位点结合，为其中和效力提供了一个机理解释。
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