Wijesinghe Kaveesha J, Stahelin Robert V
Department of Chemistry and Biochemistry, Eck Institute for Global Health, and Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, USA.
Department of Chemistry and Biochemistry, Eck Institute for Global Health, and Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, USA Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, Indiana, USA
J Virol. 2015 Dec 30;90(6):3074-85. doi: 10.1128/JVI.02607-15.
Marburg virus (MARV), which belongs to the virus family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates that is often fatal. MARV is a lipid-enveloped virus that during the replication process extracts its lipid coat from the plasma membrane of the host cell it infects. MARV carries seven genes, one of which encodes its matrix protein VP40 (mVP40), which regulates the assembly and budding of the virions. Currently, little information is available on mVP40 lipid binding properties. Here, we have investigated the in vitro and cellular mechanisms by which mVP40 associates with lipid membranes. mVP40 associates with anionic membranes in a nonspecific manner that is dependent upon the anionic charge density of the membrane. These results are consistent with recent structural determination of mVP40, which elucidated an mVP40 dimer with a flat and extensive cationic lipid binding interface.
Marburg virus (MARV) is a lipid-enveloped filamentous virus from the family Filoviridae. MARV was discovered in 1967, and yet little is known about how its seven genes are used to assemble and form a new viral particle in the host cell it infects. The MARV matrix protein VP40 (mVP40) underlies the inner leaflet of the virus and regulates budding from the host cell plasma membrane. In vitro and cellular assays in this study investigated the mechanism by which mVP40 associates with lipids. The results demonstrate that mVP40 interactions with lipid vesicles or the inner leaflet of the plasma membrane are electrostatic but nonspecific in nature and are dependent on the anionic charge density of the membrane surface. Small molecules that can disrupt lipid trafficking or reduce the anionic charge of the plasma membrane interface may be useful in inhibiting assembly and budding of MARV.
马尔堡病毒（MARV）属于丝状病毒科，可导致人类和非人类灵长类动物出现出血热，且往往致命。MARV是一种包膜病毒，在复制过程中从其感染的宿主细胞的质膜中获取脂质包膜。MARV携带七个基因，其中一个编码其基质蛋白VP40（mVP40），该蛋白调节病毒粒子的组装和出芽。目前，关于mVP40脂质结合特性的信息很少。在这里，我们研究了mVP40与脂质膜结合的体外和细胞机制。mVP40以非特异性方式与阴离子膜结合，这取决于膜的阴离子电荷密度。这些结果与最近对mVP40的结构测定一致，该测定阐明了具有平坦且广泛的阳离子脂质结合界面的mVP40二聚体。
马尔堡病毒（MARV）是一种来自丝状病毒科的包膜丝状病毒。MARV于1967年被发现，但对于其七个基因如何用于在其感染的宿主细胞中组装和形成新的病毒颗粒，人们知之甚少。MARV基质蛋白VP40（mVP40）位于病毒的内小叶下方，调节从宿主细胞质膜出芽。本研究中的体外和细胞试验研究了mVP40与脂质结合的机制。结果表明，mVP40与脂质囊泡或质膜内小叶的相互作用本质上是静电的但非特异性的，并且取决于膜表面的阴离子电荷密度。能够破坏脂质运输或降低质膜界面阴离子电荷的小分子可能有助于抑制MARV的组装和出芽。
