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恶性疟原虫感染无性阶段中STEVOR的表达动态及生理相关功能研究

Expression dynamics and physiologically relevant functional study of STEVOR in asexual stages of Plasmodium falciparum infection.

作者信息

Singh Himanshu, Madnani Kripa, Lim Ying Bena, Cao Jianshu, Preiser Peter R, Lim Chwee Teck

机构信息

Department of Biomedical Engineering, National University of Singapore, Singapore.

Infectious Diseases IRG, Singapore-MIT Alliance for Research and Technology, Singapore.

出版信息

Cell Microbiol. 2017 Jun;19(6). doi: 10.1111/cmi.12715. Epub 2017 Jan 24.

DOI:10.1111/cmi.12715
PMID:28030753
Abstract

The extensive modification of Plasmodium falciparum-infected erythrocytes by variant surface antigens plays a major role in immune evasion and malaria-induced pathology. Here, using high-resolution microscopy, we visualize the spatio-temporal expression dynamics of STEVOR, an important variant surface antigens family, in a stage-dependent manner. We demonstrate that it is exported to the cell surface where protein molecules cluster and preferentially localize in proximity to knobs. Quantitative evidence from our force measurements and microfluidic assays reveal that STEVOR can effectively mediate the formation of stable, robust rosettes under static and physiologically relevant flow conditions. Our results extend previously published studies in P. falciparum and emphasize the role of STEVOR in rosetting, an important contributor to disease pathology.

摘要

恶性疟原虫感染的红细胞被可变表面抗原广泛修饰,这在免疫逃避和疟疾诱发的病理过程中起主要作用。在此,我们使用高分辨率显微镜,以阶段依赖的方式可视化了重要的可变表面抗原家族STEVOR的时空表达动态。我们证明它被转运到细胞表面,在那里蛋白质分子聚集并优先定位在凸起附近。我们的力测量和微流控分析的定量证据表明,在静态和生理相关流动条件下,STEVOR可以有效地介导稳定、坚固的玫瑰花结的形成。我们的结果扩展了先前发表的关于恶性疟原虫的研究,并强调了STEVOR在玫瑰花结形成中的作用,玫瑰花结形成是疾病病理的一个重要因素。

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