Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport.

Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport.
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DOI:
10.1016/j.chom.2008.02.001
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发表时间:
2008-03
影响因子:
30.3
通讯作者:
S. Yamayoshi;T. Noda;H. Ebihara;H. Goto;Y. Morikawa;I. Lukashevich;G. Neumann;H. Feldmann;Y. Kawaoka
S. Yamayoshi;T. Noda;H. Ebihara;H. Goto;Y. Morikawa;I. Lukashevich;G. Neumann;H. Feldmann;Y. Kawaoka
中科院分区:
医学1区
文献类型:
--
作者:
S. Yamayoshi;T. Noda;H. Ebihara;H. Goto;Y. Morikawa;I. Lukashevich;G. Neumann;H. Feldmann;Y. Kawaoka

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埃博拉病毒基质蛋白VP40在病毒体形成和病毒从细胞中排出中起重要作用。然而,宿主细胞蛋白和机制负责细胞内运输的VP40之前,它的贡献病毒粒子的形成仍有待阐明。因此,我们使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,Sec24C,主机COPII囊泡转运系统的一个组成部分,通过VP40氨基酸303至307与VP40特异性相互作用。免疫共沉淀和显性阴性突变体研究表明,COPII转运系统在VP40细胞内转运到质膜中起着关键作用。马尔堡病毒VP40也显示使用COPII转运系统进行细胞内转运。这些发现确定了宿主途径和丝状病毒复制之间的保守交叉点,这种交叉点可以在开发新的抗病毒药物时成为目标。
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.