Bavari Sina, Bosio Catharine M, Wiegand Elizabeth, Ruthel Gordon, Will Amy B, Geisbert Thomas W, Hevey Michael, Schmaljohn Connie, Schmaljohn Alan, Aman M Javad
Dept. of Cell Biology and Biochemistry, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA.
J Exp Med. 2002 Mar 4;195(5):593-602. doi: 10.1084/jem.20011500.
Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses.
丝状病毒进入和释放的时空特征目前还知之甚少。脂筏作为多种细胞信号传导和运输过程的功能平台。在此，我们报道了埃博拉病毒和马尔堡病毒蛋白在病毒组装和出芽过程中在脂筏内的区室化。从感染细胞释放的丝状病毒掺入了与脂筏相关的分子，这表明病毒的释放发生在脂筏处。埃博拉病毒基质蛋白和糖蛋白的异位表达支持丝状病毒样颗粒（VLP）依赖脂筏的释放，通过电子显微镜观察发现其与活病毒极为相似。我们的研究结果还表明，丝状病毒的进入需要功能性脂筏，确定脂筏为病毒攻击的位点。将脂筏鉴定为丝状病毒进入和退出的通道以及VLP依赖脂筏的产生，对于开发针对埃博拉病毒和马尔堡病毒感染的治疗方法和疫苗接种策略具有重要意义。
