Inhibition of nuclear import and alteration of nuclear pore complex composition by rhinovirus.
Nucleocytoplasmic trafficking pathways and the status of nuclear pore complex (NPC) components were examined in cells infected with rhinovirus type 14. A variety of shuttling and nonshuttling nuclear proteins, using multiple nuclear import pathways, accumulated in the cytoplasm of cells infected with rhinovirus. An in vitro nuclear import assay with semipermeabilized infected cells confirmed that nuclear import was inhibited and that docking of nuclear import receptor-cargo complexes at the cytoplasmic face of the NPC was prevented in rhinovirus-infected cells. The relocation of cellular proteins and inhibition of nuclear import correlated with the degradation of two NPC components, Nup153 and p62. The degradation of Nup153 and p62 was not due to induction of apoptosis, because p62 was not proteolyzed in apoptotic HeLa cells, and Nup153 was cleaved to produce a 130-kDa cleavage product that was not observed in cells infected with poliovirus or rhinovirus. The finding that both poliovirus and rhinovirus cause inhibition of nuclear import and degradation of NPC components suggests that this may be a common feature of the replicative cycle of picornaviruses. Inhibition of nuclear import is predicted to result in the cytoplasmic accumulation of a large number of nuclear proteins that could have functions in viral translation, RNA synthesis, packaging, or assembly. Additionally, inhibition of nuclear import also presents a novel strategy whereby cytoplasmic RNA viruses can evade host immune defenses by preventing signal transduction into the nucleus.
Gustin
Kurt E
KE
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
Sarnow
Peter
P
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D001324:Autoantigens / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology*; D003593:Cytoplasm / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D012229:Rhinovirus / Q000472:pathogenicity* / Q000502:physiology; D012261:Ribonucleoproteins / Q000502:physiology; D000071456:Sequestosome-1 Protein; D000097585:SS-B Antigen
D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; D028861:Nuclear Pore Complex Proteins; D012261:Ribonucleoproteins; D000071456:Sequestosome-1 Protein; D000097585:SS-B Antigen; C079377:NUP153 protein, human; C099718:SQSTM1 protein, human