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肝素的 O-硫酸基团对于肝素抑制嗜性鼠白血病病毒感染至关重要。

O-sulfate groups of heparin are critical for inhibition of ecotropic murine leukemia virus infection by heparin.

机构信息

Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan.

出版信息

Virology. 2012 Mar 1;424(1):56-66. doi: 10.1016/j.virol.2011.11.030. Epub 2012 Jan 9.

Abstract

There is increasing evidence that soluble glycosaminoglycans such as heparin can interfere with the infectivity of various viruses, including ecotropic murine leukemia viruses (MLVs). The ecotropic MLV, Friend MLV (F-MLV) and the neuropathogenic variants A8 MLV and PVC-211 MLV, were susceptible to heparin-mediated inhibition of infection of NIH 3T3 cells. To investigate the interaction between the envelope glycoprotein (Env) of MLV and heparin, we prepared vesicular stomatitis virus-based pseudotyped viruses carrying the Env of F-, A8, or PVC-211 MLVs. Surface plasmon resonance analyses indicated that the Env of A8 and PVC-211 MLVs had a higher binding activity to heparin than that of F-MLV. We examined the influence of N- or O-sulfation of heparin on binding activity to Env and on the inhibition of the infectivity of MLV and pseudotyped viruses carrying Env. This analysis indicated that the O-sulfate groups of heparin play a major role in determining Env-dependent inhibitory effects.

摘要

越来越多的证据表明,硫酸乙酰肝素等可溶性糖胺聚糖可以干扰多种病毒的感染性,包括嗜性鼠白血病病毒(MLV)。嗜性 MLV、Friend MLV(F-MLV)和神经致病性变异株 A8 MLV 和 PVC-211 MLV 都容易受到肝素介导的 NIH 3T3 细胞感染抑制。为了研究 MLV 包膜糖蛋白(Env)与肝素之间的相互作用,我们制备了基于水疱性口炎病毒的假型病毒,携带 F-MLV、A8 或 PVC-211 MLV 的 Env。表面等离子体共振分析表明,A8 和 PVC-211 MLV 的 Env 与肝素的结合活性高于 F-MLV。我们研究了肝素的 N-或 O-硫酸化对与 Env 结合活性以及对 MLV 和携带 Env 的假型病毒感染性的抑制的影响。该分析表明,肝素的 O-硫酸基团在决定 Env 依赖性抑制作用方面起着主要作用。

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