Differential targeting of nuclear pore complex proteins in poliovirus-infected cells.
Poliovirus disrupts nucleocytoplasmic trafficking and results in the cleavage of two nuclear pore complex (NPC) proteins, Nup153 and Nup62. The NPC is a 125-MDa complex composed of multiple copies of 30 different proteins. Here we have extended the analysis of the NPC in infected cells by examining the status of Nup98, an interferon-induced NPC protein with a major role in mRNA export. Our results indicate that Nup98 is targeted for cleavage after infection but that this occurs much more rapidly than it does for Nup153 and Nup62. In addition, we find that cleavage of these NPC proteins displays differential sensitivity to the viral RNA synthesis inhibitor guanidine hydrochloride. Inhibition of nuclear import and relocalization of host nuclear proteins to the cytoplasm were only apparent at later times after infection when all three nucleoporins (Nups) were cleaved. Surprisingly, analysis of the distribution of mRNA in infected cells revealed that proteolysis of Nup98 did not result in an inhibition of mRNA export. Cleavage of Nup98 could be reconstituted by the addition of purified rhinovirus type 2 2A(pro) to whole-cell lysates prepared from uninfected cells, suggesting that the 2A protease has a role in this process in vivo. These results indicate that poliovirus differentially targets subsets of NPC proteins at early and late times postinfection. In addition, targeting of interferon-inducible NPC proteins, such as Nup98, may be an additional weapon in the arsenal of poliovirus and perhaps other picornaviruses to overcome host defense mechanisms.
Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, ID 83844-3052, USA.
Nogi
N
Park
Pavan
P
Katikaneni
Tim
T
Skern
Kurt E
KE
Gustin
D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000032:analysis / Q000378:metabolism*; D017955:Poliovirus / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D008562:Membrane Glycoproteins; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; C093350:nuclear pore complex protein 98; C049312:nuclear pore protein p62