埃博拉病毒的基質(zhì)蛋白VP40對病毒的組裝和釋放發(fā)揮著關(guān)鍵作用。早在病毒產(chǎn)生之前,，VP40蛋白就轉(zhuǎn)移至細胞膜，在質(zhì)膜上釋放埃博拉病毒,。
在最新研究中,，Yamayoshi等人發(fā)現(xiàn)，VP40蛋白利用宿主COPII的機械傳輸運動，通過與Sec24C（COPII的一個組成部分）相互作用而達到細胞內(nèi)遷移,。封面的照片顯示了細胞表達VP40的掃描電鏡照片,。釋放絲狀埃博拉病毒樣的顆粒從細胞表面凸現(xiàn)。
埃博拉病毒的基質(zhì)蛋白VP40在病毒體形成與病毒的釋放過程中發(fā)揮著重要的作用,。然而，宿主細胞與病毒蛋白VP40的作用,，以及VP40在病毒胞內(nèi)運輸與病毒顆粒形成過程中的作用還不清楚,。為此，Yamayoshi等運用免疫沉淀反應(yīng)和質(zhì)譜等分析方法研究了宿主蛋白與VP40的相互作用,。
結(jié)果表明,，宿主COPII泡狀傳輸系統(tǒng)的組成部分——Sec24C，特異性地結(jié)合VP40的303與307號氨基酸,，從而達到與VP40結(jié)合的目的,。免疫沉淀反應(yīng)和顯性負突變體的實驗顯示，COPII傳輸系統(tǒng)對于VP40從胞內(nèi)遷移至細胞質(zhì)膜的過程中起著關(guān)鍵作用,。同時,，馬爾堡病毒VP40也顯示了COPII運輸系統(tǒng)在病毒胞內(nèi)轉(zhuǎn)移中發(fā)揮的作用。
該研究確定了宿主和纖絲病毒復(fù)制之間的相互作用位點,，據(jù)此人們可以有針對性地開發(fā)新的抗病毒藥物,。相關(guān)論文發(fā)表在3月13日的《細胞—宿主與微生物》上。（科學(xué)網(wǎng) 武彥文/編譯）
生物谷推薦原始出處：
（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.
