Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Virol. 2010 May;84(9):4816-20. doi: 10.1128/JVI.00010-10. Epub 2010 Feb 17.
The Ebolavirus matrix protein VP40 is essential for virion assembly and egress. Recently, we reported that the coat protein complex II (COPII) transport system plays an important role in the transport of VP40 to the plasma membrane. Here, we show that dominant-negative mutants of the GTPase Rab1b interfere with VP40-mediated particle formation. Rab1b activates GBF1 (Golgi-specific BFA [brefeldin A] resistance factor 1), a critical factor in the assembly of COPI vesicles. Activated GBF1 stimulates ARF1 (ADP ribosylation factor 1), which recruits coat protein to cellular membranes for the assembly of COPI vesicles. Here, we demonstrate that GBF1 and ARF1 are involved in Ebolavirus virion formation, suggesting that both the COPII and COPI transport systems play a role in Ebolavirus VP40-mediated particle formation. These findings provide new insights into the cellular pathways employed for Ebolavirus virion formation.
埃博拉病毒基质蛋白 VP40 对于病毒粒子的组装和出芽是必不可少的。最近,我们报道称,衣壳蛋白复合物 II(COPII)运输系统在 VP40 向质膜的运输中起着重要作用。在这里,我们表明,GTPase Rab1b 的显性负突变体干扰 VP40 介导的颗粒形成。Rab1b 激活 GBF1(高尔基特异性 BFA [布雷菲德菌素 A]抗性因子 1),这是 COPI 囊泡组装的关键因素。激活的 GBF1 刺激 ARF1(ADP 核糖基化因子 1),它将衣壳蛋白募集到细胞膜上,用于 COPI 囊泡的组装。在这里,我们证明 GBF1 和 ARF1 参与埃博拉病毒病毒粒子的形成,这表明 COPII 和 COPI 运输系统都在埃博拉病毒 VP40 介导的颗粒形成中发挥作用。这些发现为埃博拉病毒病毒粒子形成所利用的细胞途径提供了新的见解。