Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral replication

Wen-Fang Tang, Shing Ying Yang, Bin Wen Wu, Jia Rong Jheng, Yin Li Chen, Chung Hsuan Shih, Kwang Huei Lin, Hsin Chi Lai, Petrus Tang, Jim Tong Horng*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

135 引文 斯高帕斯(Scopus)

摘要

Enterovirus 71 is an enterovirus of the family Picornaviridae. The 2C protein of poliovirus, a relative of enterovirus 71, is essential for viral replication. The poliovirus 2C protein is associated with host membrane vesicles, which form viral replication complexes where viral RNA synthesis takes place. We have now identified a host-encoded 2C binding protein called reticulon 3, which we found to be associated with the replication complex through direct interaction with the enterovirus 71-encoded 2C protein. We observed that the N terminus of the 2C protein, which has both RNA- and membrane-binding activity, interacted with reticulon 3. This region of interaction was mapped to its reticulon homology domain, whereas that of 2C was encoded by the 25th amino acid, isoleucine. Reticulon 3 could also interact with the 2C proteins encoded by other enteroviruses, such as poliovirus and coxsackievirus A16, implying that it is a common factor for such viral replication. Reduced production of reticulon 3 by RNA interference markedly reduced the synthesis of enterovirus 71-encoded viral proteins and replicative doublestranded RNA, reducing plaque formation and apoptosis. Furthermore, reintroduction of nondegradable reticulon 3 into these knockdown cells rescued enterovirus 71 infectivity, and viral protein and double-stranded RNA synthesis. Thus, reticulon 3 is an important component of enterovirus 71 replication, through its potential role in modulation of the sequential interactions between enterovirus 71 viral RNA and the replication complex.

原文英語
頁(從 - 到)5888-5898
頁數11
期刊Journal of Biological Chemistry
282
發行號8
DOIs
出版狀態已出版 - 23 02 2007

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