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Review
. 2003 Sep;95(1-2):35-44.
doi: 10.1016/s0168-1702(03)00165-5.

Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

Kurt E Gustin  1
Affiliations
Review

Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

Kurt E Gustin. Virus Res. 2003 Sep.

Abstract

Analysis of virus-host interactions has revealed a variety of ways in which viruses utilize and/or alter host functions in an effort to facilitate efficient replication. Recent work has suggested that certain RNA viruses that replicate in the cytoplasm disrupt the normal trafficking of cellular RNAs and proteins within the host cell. This review will examine the recent evidence showing that poliovirus and vesicular stomatitis virus (VSV) can inhibit nucleo-cytoplasmic transport within cells. Interestingly, the data indicate that inhibition by both viruses involves targeting components of the nuclear pore complex (NPC). Following this, several possible explanations for why viruses might disrupt nucleo-cytoplasmic transport are discussed. Finally, the possibility that disruption of nucleo-cytoplasmic trafficking may be a more common feature of RNA virus-host interactions than previously thought is examined.

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Figures

Fig. 1
Fig. 1
Schematic representation of the NPC. Major structural features discussed in the text are illustrated, including cytoplasmic fibrils and the nuclear basket. Approximate location of various Nups are shown. NE, nuclear envelope.
Fig. 2
Fig. 2
Relocalization of EGFP-NLS molecules in poliovirus-infected cells. (A) HeLa cells stably expressing EGFP were mock-infected or infected with poliovirus as indicated. Cells were processed and examined by fluorescent microscopy at 4.5 h after infection. EGFP fluorescence was visualized using a FITC filter. DNA: Hoechst-stained nuclei were examined with a UV filter. Merged: shows the FITC and Hoechst images merged. (B) HeLa cells stably expressing EGFP-NLS fusion proteins were examined as described in (A). Adapted from Gustin and Sarnow (2001), with permission.
Fig. 3
Fig. 3
Nucleo-cytoplasmic trafficking of a glucocorticoid receptor-HIV REV fusion protein proceeds normally in poliovirus-infected cells. (A) HeLa cells were transiently transfected with a plasmid that encodes the REV–GC–GFP fusion protein; after 40 h, cells were either mock-infected (Mock-infected) or infected with poliovirus (Poliovirus-infected). Four hours after infection cells were untreated (−hormone) or treated with dexamethasone (+hormone) at 1 μM for 30 min prior to fixation. (B) Cells were transfected as described above and 40 h later were either mock-infected or infected with poliovirus and dexamethasone was added. Two hours later the cells were either fixed (+hormone), or dexamethasone was removed by washing once with PBS and adding fresh medium. Cells were processed for fluorescent microscopy 2 h after removal of dexamethasone (−hormone 2 h). (C) Same as in (B) except that leptomycin B (5 ng/ml, +LMB) was added following removal of dexamethasone. Top panels show GFP using a FITC filter and bottom panels show Hoechst staining of the same field using a UV filter. Adapted from Gustin and Sarnow (2001), with permission.
Fig. 4
Fig. 4
Degradation of NPC proteins in poliovirus-infected HeLa cells. (A) Fifty μg of whole cell lysates prepared from mock-infected cells or cells that had been infected with rhinovirus for the indicated length of time were analyzed by immunoblotting with monoclonal antibody 414 to detect Nup153 and p62, or MS3 to detect nucleolin. Adapted from Gustin and Sarnow (2001), with permission. (B) Changes to the NPC and transport pathways caused by poliovirus infection. X indicates transport pathway disrupted or Nup degraded. Question marks indicate that the status of these Nups in the NPC has not been determined. NE, nuclear envelope.
Fig. 4
Fig. 4
Degradation of NPC proteins in poliovirus-infected HeLa cells. (A) Fifty μg of whole cell lysates prepared from mock-infected cells or cells that had been infected with rhinovirus for the indicated length of time were analyzed by immunoblotting with monoclonal antibody 414 to detect Nup153 and p62, or MS3 to detect nucleolin. Adapted from Gustin and Sarnow (2001), with permission. (B) Changes to the NPC and transport pathways caused by poliovirus infection. X indicates transport pathway disrupted or Nup degraded. Question marks indicate that the status of these Nups in the NPC has not been determined. NE, nuclear envelope.
Fig. 5
Fig. 5
Changes to the NPC and transport pathways caused by the VSV M protein. VSV M is thought to associate with Nup98 on the nucleoplasmic side of the NPC, but may also associate with other NPC components. The precise location of VSV M or the number of molecules present at the NPC is not known. X indicates transport pathway disrupted. NE, nuclear envelope.
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