Department of Chemistry, Pittsburg State University, 1701 S. Broadway Street, Pittsburg, KS, 66762, USA.
Sci Rep. 2017 Aug 7;7(1):7377. doi: 10.1038/s41598-017-07620-y.
The aim of this research is twofold: 1) to shed light on zika's binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time. In addition, the role of crizotinib as a potential binding inhibitor is demonstrated and the possibility of ligand-independent phosphatidylserine-mediated binding is explored. Our findings suggest that while the extracellular domain of AXL has the highest affinity for ZENV; HSP70, TIM-1, and phosphatidylserine might also play active roles in zika tropism, which offers a potential explanation for the variety of zika-associated symptoms. This is, to our knowledge, the first time that MRNPs have been used to examine and quantify host-zika interactions. Our magnetic relaxation platform allows for timely and sensitive analysis of these intricate binding relationships, and it is easily customizable for further examination of additional host-pathogen interactions.
1)阐明寨卡病毒的结合和进入机制,2)展示我们的磁共振弛豫平台实现这一目标的有效性。我们创新性地使用磁共振弛豫敏感纳米颗粒(MRNPs)来分析寨卡包膜蛋白(ZENV)与潜在宿主细胞受体(AXL、HSP70 和 TIM-1)之间的结合相互作用。我们还首次利用计算分析来研究这些结合相互作用。此外,我们还证明了克唑替尼作为一种潜在结合抑制剂的作用,并探讨了配体非依赖性磷脂酰丝氨酸介导结合的可能性。我们的研究结果表明,尽管 AXL 的细胞外结构域与 ZENV 具有最高的亲和力;但 HSP70、TIM-1 和磷脂酰丝氨酸也可能在寨卡病毒嗜性中发挥积极作用,这为寨卡病毒相关症状的多样性提供了潜在解释。据我们所知,这是首次使用 MRNPs 来检测和量化宿主-寨卡病毒相互作用。我们的磁共振弛豫平台允许对这些复杂的结合关系进行及时和敏感的分析,并且易于定制,以进一步研究其他宿主-病原体相互作用。