埃博拉病毒实现胞内迁移的工具

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埃博拉病毒的基质蛋白VP40对病毒的组装和释放发挥着关键作用。早在病毒产生之前，VP40蛋白就转移至细胞膜，在质膜上释放埃博拉病毒。

在最新研究中，Yamayoshi等人发现，VP40蛋白利用宿主COPII的机械传输运动，通过与Sec24C（COPII的一个组成部分）相互作用而达到细胞内迁移。封面的照片显示了细胞表达VP40的扫描电镜照片。释放丝状埃博拉病毒样的颗粒从细胞表面凸现。

埃博拉病毒的基质蛋白VP40在病毒体形成与病毒的释放过程中发挥着重要的作用。然而，宿主细胞与病毒蛋白VP40的作用，以及VP40在病毒胞内运输与病毒颗粒形成过程中的作用还不清楚。为此，Yamayoshi等运用免疫沉淀反应和质谱等分析方法研究了宿主蛋白与VP40的相互作用。

结果表明，宿主COPII泡状传输系统的组成部分——Sec24C，特异性地结合VP40的303与307号氨基酸，从而达到与VP40结合的目的。免疫沉淀反应和显性负突变体的实验显示，COPII传输系统对于VP40从胞内迁移至细胞质膜的过程中起着关键作用。同时，马尔堡病毒VP40也显示了COPII运输系统在病毒胞内转移中发挥的作用。

该研究确定了宿主和纤丝病毒复制之间的相互作用位点，据此人们可以有针对性地开发新的抗病毒药物。相关论文发表在3月13日的《细胞—宿主与微生物》上。


（Cell Host & Microbe），Vol 3, 168-177, 13 March 2008，Seiya Yamayoshi, Yoshihiro Kawaoka

Ebola Virus Matrix Protein VP40 Uses the COPII Transport System for Its Intracellular Transport
Seiya Yamayoshi,1,2 Takeshi Noda,2,3 Hideki Ebihara,2,3,4 Hideo Goto,1,2 Yuko Morikawa,5 Igor S. Lukashevich,6 Gabriele Neumann,7 Heinz Feldmann,4 and Yoshihiro Kawaoka1,2,3,7,

1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
2 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan
3 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
4 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
5 Kitasato Institute for Life Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan
6 Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA
7 Department of Pathological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA


Corresponding author

Summary


The Ebola virus matrix protein VP40 plays an important role in virion formation and viral egress from cells. However, the host cell proteins and mechanisms responsible for intracellular transport of VP40 prior to its contribution to virion formation remain to be elucidated. Therefore we used coimmunoprecipitation and mass spectrometric analyses to identify host proteins interacting with VP40. We found that Sec24C, a component of the host COPII vesicular transport system, interacts specifically with VP40 via VP40 amino acids 303 to 307. Coimmunoprecipitation and dominant-negative mutant studies indicated that the COPII transport system plays a critical role in VP40 intracellular transport to the plasma membrane. Marburg virus VP40 was also shown to use the COPII transport system for intracellular transport. These findings identify a conserved intersection between a host pathway and filovirus replication, an intersection that can be targeted in the development of new antiviral drugs.