Kleijn M, Vrins C L, Voorma H O, Thomas A A
Department of Molecular Cell Biology, University of Utrecht, The Netherlands.
Virology. 1996 Mar 15;217(2):486-94. doi: 10.1006/viro.1996.0143.
The eukaryotic translation initiation factor eIF4E, the cap-binding protein, seems to play an essential role in the establishment of the host shut-off after viral infection. Infection with adenovirus and influenza virus caused dephosphorylation of eIF4E and an involvement of a viral protein was suggested. In this report, we studied several other viruses for their ability to change the phosphorylation state of eIF4E, and we looked for the mechanism of eIF4E dephosphorylation. First, it was shown that after encephalomyocarditis virus (EMCV) and poliovirus infection, dephosphorylation of eIF4E occurred. Dephosphorylation of eIF4E was not observed after Semliki Forest virus and reovirus infection. An artificial increase of the level of phosphorylated eIF4E by treating the cells with the phosphatase inhibitor okadaic acid changed neither the kinetics of EMCV and poliovirus infection, nor that of host shut-off. Infections with the uv-treated EMCV showed that the virus binding or entry into the cell initiates eIF4E dephosphorylation. Besides this entry-induced eIF4E dephosphorylation, dephosphorylation was also induced by blocking protein synthesis with the initiation inhibitor pactamycin, or with the elongation inhibitor cycloheximide. We conclude that eIF4E is dephosphorylated by entry of EMCV, and the effect is strengthened by the decrease in cap-dependent translation.
真核生物翻译起始因子eIF4E，即帽结合蛋白，似乎在病毒感染后宿主关闭机制的建立中起关键作用。腺病毒和流感病毒感染会导致eIF4E去磷酸化，提示有病毒蛋白参与其中。在本报告中，我们研究了其他几种病毒改变eIF4E磷酸化状态的能力，并探寻eIF4E去磷酸化的机制。首先，研究表明脑心肌炎病毒（EMCV）和脊髓灰质炎病毒感染后，eIF4E会发生去磷酸化。而辛德毕斯病毒和呼肠孤病毒感染后未观察到eIF4E去磷酸化。用磷酸酶抑制剂冈田酸处理细胞人为提高磷酸化eIF4E的水平，既未改变EMCV和脊髓灰质炎病毒感染的动力学，也未改变宿主关闭的动力学。用紫外线处理过的EMCV进行感染表明，病毒与细胞的结合或进入会引发eIF4E去磷酸化。除了这种进入诱导的eIF4E去磷酸化外，用起始抑制剂 pactamycin或延伸抑制剂环己酰亚胺阻断蛋白质合成也可诱导去磷酸化。我们得出结论，EMCV的进入会使eIF4E去磷酸化，帽依赖性翻译的减少会增强这种效应。
