National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
Virology. 2012 Mar 30;425(1):11-22. doi: 10.1016/j.virol.2011.12.022. Epub 2012 Jan 24.
Poxviruses are large double-stranded DNA viruses that replicate exclusively in the cytoplasm of infected cells within discrete compartments termed viral factories. Recent work has shown that the prototypical poxvirus, Vaccinia Virus (VacV) sequesters components of the eukaryotic translation initiation complex eIF4F within viral factories while also stimulating formation of eIF4F complexes. However, the forces that govern these events remain unknown. Here, we show that maximal eIF4F formation requires viral DNA replication and the formation of viral factories, suggesting that sequestration functions to promote eIF4F assembly, and identify the ssDNA-binding protein, I3 as a viral factor that interacts and co-localizes with the eIF4F scaffold protein, eIF4G. Although it did not adversely affect host or viral protein synthesis, I3 specifically mediated the binding of eIF4G to ssDNA. Combined, our findings offer an explanation for the specific pattern and temporal process of eIF4G redistribution and eIF4F complex assembly within VacV-infected cells.
痘病毒是大型双链 DNA 病毒，仅在称为病毒工厂的离散隔室中在受感染细胞的细胞质中复制。最近的研究表明，典型的痘病毒，牛痘病毒 (VacV) 将真核翻译起始复合物 eIF4F 的成分隔离在病毒工厂内，同时刺激 eIF4F 复合物的形成。然而，控制这些事件的力量仍然未知。在这里，我们表明最大的 eIF4F 形成需要病毒 DNA 复制和病毒工厂的形成，这表明隔离功能促进 eIF4F 组装，并确定 ssDNA 结合蛋白 I3 作为与 eIF4F 支架蛋白 eIF4G 相互作用和共定位的病毒因子。尽管它没有不利地影响宿主或病毒蛋白的合成，但 I3 特异性地介导了 eIF4G 与 ssDNA 的结合。总之，我们的研究结果为 VacV 感染细胞中 eIF4G 重分布和 eIF4F 复合物组装的特定模式和时间过程提供了一个解释。
