Polio Cripples Nuclear Import

Abstract

The replicative cycle of poliovirus occurs entirely in the cytoplasm of the infected cell. Poliovirus-infected cells exhibit redistribution of several nuclear proteins to the cytosol. Gustin and Sarnow show that poliovirus disrupts multiple nuclear import pathways in virally infected cells: (i) the classical import pathway that recognizes proteins with a nuclear localization signal (NLS), (ii) the transportin import pathway that recognizes proteins with an M9 NLS consisting of a glycine-rich motif, (iii) and the KNS import pathway involved in transporting the heterogenous nuclear ribonucleoprotein K (hnRNP K). In cell-free import and export assays, poliovirus inhibited an early step in nuclear translocation that prevents docking at the nuclear pore complex (NPC), but did not inhibit nuclear export mediated by the nuclear export signal receptor Crm1. Examination of components of the NPC recognized by antibody 414 suggested that at least two NPC proteins were specifically degraded in poliovirus-infected cells; however, the nuclear envelope was not generally disrupted based on normal immunofluorescent staining by an antibody against nuclear lamins. Thus, selective degradation of components of the NPC may disrupt specific nuclear import pathways. This could disrupt cellular signaling pathways, subvert apoptotic responses to infection, as well as redistribute nuclear proteins necessary for viral replication. K. E. Gustin, P. Sarnow, Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition. EMBO J. 20 , 240-249 (2001). [Abstract] [Full Text]