Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
Virology. 2012 Mar 30;425(1):40-52. doi: 10.1016/j.virol.2011.12.019. Epub 2012 Jan 26.
Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C(pro) induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm. The siRNA knockdown of Sam68 resulted in a 1000-fold reduction in viral titers, which prompted us to study the effect of Sam68 on FMDV post-entry events. Interestingly, Sam68 interacts with the internal ribosomal entry site within the 5' non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome. The results uncover a novel role for Sam68 in the context of picornaviruses and the proteolysis of a new cellular target of the FMDV 3C(pro).
小核糖核酸病毒感染可导致核孔运输中断、细胞翻译机制关闭，并切割参与细胞信号转导和感染固有反应的蛋白质。在这里，我们证明了口蹄疫病毒 3C(pro)诱导核 RNA 结合蛋白 Sam68 含核定位序列 (NLS) 的 C 端裂解。结果，它刺激 Sam68 向细胞质重新分布。Sam68 的 siRNA 敲低导致病毒滴度降低 1000 倍，这促使我们研究 Sam68 对口蹄疫病毒进入后事件的影响。有趣的是，Sam68 与口蹄疫病毒基因组 5'非翻译区内部核糖体进入位点相互作用，Sam68 敲低降低了体外口蹄疫病毒 IRES 驱动的活性，表明它可以调节病毒基因组的翻译。结果揭示了 Sam68 在小核糖核酸病毒背景下以及口蹄疫病毒 3C(pro)对新的细胞靶标的蛋白水解中的新作用。
