Filovirus Laboratory, INSERM U758, Human Virology Department, Claude Bernard Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
J Infect Dis. 2011 Nov;204 Suppl 3:S884-91. doi: 10.1093/infdis/jir359.
The matrix protein VP40 is essential for Ebola virus (EBOV) and Marburg virus assembly and budding at the plasma membrane. In this study we have investigated the effect of single amino acid substitutions in a conserved proline-rich region of the EBOV VP40 located in the carboxy-terminal part of the protein. We demonstrate that substitutions within this region result in an alteration of intracellular VP40 localization and also cause a reduction or a complete block of virus-like particle budding, a benchmark of VP40 function. Furthermore, some mutated VP40s revealed an enhanced binding with cellular Sec24C, a part of the coat protein complex II (COPII) vesicular transport system. Analysis of the 3-dimensional structure of VP40 revealed the spatial proximity of the proline-rich region and an earlier identified site of interaction with Sec24C, thus allowing us to hypothesize that the altered intracellular localization of the VP40 mutants is a consequence of defects in their interaction with COPII-mediated vesicular transport.
基质蛋白 VP40 对于埃博拉病毒（EBOV）和马尔堡病毒在质膜处的组装和出芽是必需的。在这项研究中，我们研究了位于蛋白质羧基端的 EBOV VP40 保守脯氨酸丰富区单个氨基酸取代的影响。我们证明，该区域内的取代导致细胞内 VP40 定位的改变，并且还导致病毒样颗粒出芽的减少或完全阻断，这是 VP40 功能的一个基准。此外，一些突变的 VP40 与细胞 Sec24C 的结合增强，Sec24C 是衣壳蛋白复合物 II（COPII）囊泡运输系统的一部分。VP40 的三维结构分析揭示了富含脯氨酸的区域与先前鉴定的与 Sec24C 相互作用位点的空间接近性，从而使我们假设 VP40 突变体的细胞内定位改变是其与 COPII 介导的囊泡运输相互作用缺陷的结果。
