Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
Sci Rep. 2017 Aug 9;7(1):7698. doi: 10.1038/s41598-017-08167-8.
Ebola virus causes devastating hemorrhagic fever outbreaks for which no approved therapeutic exists. The viral nucleocapsid, which is minimally composed of the proteins NP, VP35, and VP24, represents an attractive target for drug development; however, the molecular determinants that govern the interactions and functions of these three proteins are still unknown. Through a series of mutational analyses, in combination with biochemical and bioinformatics approaches, we identified a region on VP24 that was critical for its interaction with NP. Importantly, we demonstrated that the interaction between VP24 and NP was required for both nucleocapsid assembly and genome packaging. Not only does this study underscore the critical role that these proteins play in the viral replication cycle, but it also identifies a key interaction interface on VP24 that may serve as a novel target for antiviral therapeutic intervention.
埃博拉病毒会引起致命的出血热疫情，但目前尚无获得批准的治疗方法。病毒核衣壳由 NP、VP35 和 VP24 三种蛋白组成，是药物研发的一个有吸引力的靶点；然而，调控这三种蛋白相互作用和功能的分子决定因素尚不清楚。通过一系列的突变分析，结合生化和生物信息学方法，我们确定了 VP24 上的一个区域对于其与 NP 的相互作用至关重要。重要的是，我们证明了 VP24 与 NP 之间的相互作用对于核衣壳组装和基因组包装都是必需的。这项研究不仅强调了这些蛋白在病毒复制周期中所起的关键作用，还确定了 VP24 上的一个关键相互作用界面，它可能成为抗病毒治疗干预的一个新靶点。
