The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress.
The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress.
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DOI：
10.1038/srep19125
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发表时间：
2016-01-12
影响因子：
4.6
通讯作者：
Stahelin RV
中科院分区：
文献类型：
--
作者：
Johnson KA;Taghon GJ;Scott JL;Stahelin RV
VP40是埃博拉病毒（EBOV）编码的八种蛋白之一，作为初级基质蛋白，在不需要其他EBOV蛋白的情况下从哺乳动物细胞形成病毒样颗粒（VLPs）。虽然VP40是病毒在感染期间从宿主细胞组装和出芽所必需的，但将VP40靶向质膜的机制尚不清楚。磷脂酰丝氨酸是VP40质膜结合、VP40六聚体形成和VLP出口所必需的，然而，PS也暴露在VP40出芽部位的外膜小叶上，这就提出了当PS翻转到相反方向时VP40如何与质膜内小叶保持相互作用的问题。为了解决这个问题，我们采用细胞和体外实验来确定磷酸肌苷对VP40在质膜上的有效定位是否重要。细胞研究表明，PI(4,5)P2是VP40在质膜上组装和随后的病毒样颗粒形成的重要组成部分。此外，PI(4,5)P2是VP40广泛低聚物形成所必需的，这表明PS和PI(4,5)P2在VP40组装中具有不同的作用，其中PS调节VP40二聚体形成六聚体，而PI(4,5)P2稳定和/或诱导质膜上VP40的广泛低聚。
VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation, and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P2 was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P2 was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P2 have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P2 stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane.