Takada A, Watanabe S, Ito H, Okazaki K, Kida H, Kawaoka Y
Laboratory of Microbiology, Graduate School of Veterinary Medicine, Sapporo, 060-0818, Japan.
Virology. 2000 Dec 5;278(1):20-6. doi: 10.1006/viro.2000.0601.
Filoviruses, including Ebola virus, are cytotoxic. To investigate the role of the Ebola virus glycoprotein (GP) in this cytopathic effect, we transiently expressed the GP in human kidney 293T cells. Expression of wild-type GP, but not the secretory form of the molecule lacking a membrane anchor, induced rounding and detachment of the cells, as did a chimeric GP containing its ectodomain and influenza virus hemagglutinin transmembrane-cytoplasmic domain. These results indicate that the GP ectodomain and its anchorage to the membrane are required for GP-induced morphologic changes in host cells. Since cell rounding and detachment could be associated with reduced levels of cell adhesion molecules, we also studied the expression of integrins, which are major molecules for adhesion to extracellular matrices, and found that the beta1 integrin group is downregulated by the GP. This result was further extended by experiments in which anti-beta1 monoclonal antibodies or purified integrins inhibited the infectivity of vesicular stomatitis virus pseudotyped with the GP. We suggest that integrins, especially the beta1 group, might interact with the GP and perhaps be involved in Ebola virus entry into cells.
包括埃博拉病毒在内的丝状病毒具有细胞毒性。为了研究埃博拉病毒糖蛋白（GP）在这种细胞病变效应中的作用，我们在人肾293T细胞中瞬时表达了GP。野生型GP的表达，而非缺乏膜锚定的分子分泌形式，诱导了细胞变圆和脱离，含有其胞外域和流感病毒血凝素跨膜 - 胞质域的嵌合GP也有同样的作用。这些结果表明，GP诱导宿主细胞形态变化需要GP胞外域及其与膜的锚定。由于细胞变圆和脱离可能与细胞粘附分子水平降低有关，我们还研究了整合素的表达，整合素是与细胞外基质粘附的主要分子，发现β1整合素组被GP下调。用抗β1单克隆抗体或纯化的整合素抑制以GP为假型的水疱性口炎病毒感染性的实验进一步扩展了这一结果。我们认为整合素，尤其是β1组，可能与GP相互作用，并且可能参与埃博拉病毒进入细胞的过程。
