Gustin K E, Sarnow P
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
EMBO J. 2001 Jan 15;20(1-2):240-9. doi: 10.1093/emboj/20.1.240.
Infection of eukaryotic cells with lytic RNA viruses results in extensive interactions of viral gene products with macromolecular pathways of the host, ultimately leading to death of the infected cells. We show here that infection of cells with poliovirus results in the cytoplasmic accumulation of a variety of shuttling and non-shuttling nuclear proteins that use multiple nuclear import pathways. In vitro nuclear import assays using semi-permeabilized infected cells confirmed that nuclear import was blocked and demonstrated that docking of nuclear import receptor-cargo complexes at the cytoplasmic face of the nuclear pore complex (NPC) was prevented. Analysis of components of the NPC revealed that two proteins, Nup153 and p62, were proteolyzed during poliovirus infection. These results suggest that the cytoplasmic relocalization of numerous cellular proteins is caused by the inhibition of multiple nuclear import pathways via alterations in NPC composition in poliovirus-infected cells. Blocking of nuclear import points to a novel strategy by which cytoplasmic RNA viruses can evade host immune defenses, by preventing signal transduction to the nucleus.
溶细胞性RNA病毒感染真核细胞会导致病毒基因产物与宿主的大分子途径发生广泛相互作用，最终导致被感染细胞死亡。我们在此表明，脊髓灰质炎病毒感染细胞会导致多种穿梭和非穿梭核蛋白在细胞质中积累，这些核蛋白利用多种核输入途径。使用半透性感染细胞进行的体外核输入试验证实核输入被阻断，并表明核输入受体-货物复合物在核孔复合体（NPC）细胞质面的对接被阻止。对NPC成分的分析显示，在脊髓灰质炎病毒感染期间，两种蛋白质Nup153和p62被蛋白酶解。这些结果表明，脊髓灰质炎病毒感染细胞中NPC组成的改变通过抑制多种核输入途径导致众多细胞蛋白在细胞质中重新定位。核输入的阻断指出了一种新策略，细胞质RNA病毒可通过阻止信号转导至细胞核来逃避宿主免疫防御。
