Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition.
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.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002467:Cell Nucleus / Q000502:physiology*; D003593:Cytoplasm / Q000502:physiology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D017955:Poliovirus / Q000472:pathogenicity / Q000502:physiology*; D012261:Ribonucleoproteins / Q000032:analysis / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D014162:Transfection; D016335:Zinc Fingers
D048868:Adaptor Proteins, Signal Transducing; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008164:Luminescent Proteins; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D049452:Green Fluorescent Proteins