埃博拉病毒基质蛋白VP40利用COPII转运系统进行细胞内运输。
Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport.
作者信息
Yamayoshi Seiya, Noda Takeshi, Ebihara Hideki, Goto Hideo, Morikawa Yuko, Lukashevich Igor S, Neumann Gabriele, Feldmann Heinz, Kawaoka Yoshihiro
机构信息
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Tokyo 108-8639, Japan.
出版信息
Cell Host Microbe. 2008 Mar 13;3(3):168-77. doi: 10.1016/j.chom.2008.02.001.
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.
埃博拉病毒基质蛋白VP40在病毒粒子形成以及病毒从细胞中释放的过程中发挥着重要作用。然而，在VP40对病毒粒子形成产生作用之前，负责其细胞内运输的宿主细胞蛋白和机制仍有待阐明。因此，我们利用免疫共沉淀和质谱分析来鉴定与VP40相互作用的宿主蛋白。我们发现，宿主COPII囊泡运输系统的一个组成部分Sec24C通过VP40的303至307位氨基酸与VP40特异性相互作用。免疫共沉淀和显性负性突变体研究表明，COPII运输系统在VP40向质膜的细胞内运输中起关键作用。马尔堡病毒VP40也被证明利用COPII运输系统进行细胞内运输。这些发现确定了宿主途径与丝状病毒复制之间的一个保守交叉点，这一交叉点可作为开发新型抗病毒药物的靶点。
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