Differential targeting of nuclear pore complex proteins in poliovirus-infected cells

Nogi Park, Pavan Katikaneni, Tim Skern, Kurt E Gustin

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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 2Apro 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.

Original languageEnglish (US)
Pages (from-to)1647-1655
Number of pages9
JournalJournal of Virology
Volume82
Issue number4
DOIs
StatePublished - Feb 2008
Externally publishedYes

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Nuclear Pore Complex Proteins
nucleoporins
Enterovirus C
Poliovirus
Nuclear Pore
cells
Messenger RNA
Interferons
interferons
Picornaviridae
Nucleic Acid Synthesis Inhibitors
Rhinovirus
Weapons
Cell Nucleus Active Transport
nucleocytoplasmic transport
Guanidine
Viral RNA
Nuclear Proteins
Infection
guanidines

ASJC Scopus subject areas

  • Immunology

Cite this

Differential targeting of nuclear pore complex proteins in poliovirus-infected cells. / Park, Nogi; Katikaneni, Pavan; Skern, Tim; Gustin, Kurt E.

In: Journal of Virology, Vol. 82, No. 4, 02.2008, p. 1647-1655.

Research output: Contribution to journalArticle

Park, Nogi ; Katikaneni, Pavan ; Skern, Tim ; Gustin, Kurt E. / Differential targeting of nuclear pore complex proteins in poliovirus-infected cells. In: Journal of Virology. 2008 ; Vol. 82, No. 4. pp. 1647-1655.
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