Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through NUP62, inhibiting host nucleocytoplasmic transport pathways

Poonam Malik, Alijan Tabarraei, Ralph H Kehlenbach, Nadia Korfali, Ryota Iwasawa, Sheila V Graham, Eric C Schirmer

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The herpes simplex virus ICP27 protein is important for the expression and nuclear export of viral mRNAs. Although several binding sites have been mapped along the ICP27 sequence for various RNA and protein partners including the transport receptor TAP of the host cell nuclear transport machinery, several aspects of ICP27 trafficking through the nuclear pore complex remain unclear. We investigated if ICP27 could interact directly with the nuclear pore complex itself, finding that ICP27 directly binds the core nucleoporin Nup62. This is confirmed through co-immunoprecipitation and in vitro binding assays with purified components. Mapping with ICP27 deletion and point mutants further shows that the interaction requires sequences in both the N- and C-termini of ICP27. Expression of wild-type ICP27 protein inhibited both classical, importin α/β-dependent and transportin-dependent nuclear import. In contrast, an ICP27 point mutant that does not interact with Nup62 had no such inhibitory effect. We suggest that ICP27 association with Nup62 provides additional binding sites at the nuclear pore for ICP27 shuttling thus supporting ICP27-mediated transport. We propose that ICP27 competes with some host cell transport receptors for binding, resulting in inhibition of those host transport pathways.
Original languageEnglish
Pages (from-to)12277-12292
Number of pages16
JournalJournal of Biological Chemistry
Volume287
Issue number15
Early online date14 Feb 2012
DOIs
Publication statusPublished - 6 Apr 2012

Keywords / Materials (for Non-textual outputs)

  • Herpesvirus
  • Nuclear Pore
  • Nuclear Pore Complex (NPC)
  • Nuclear Transport
  • Protein Export
  • Protein-Protein Interactions
  • Herpes Simplex Virus Type 1 (HSV-1)
  • ICP27
  • Kaposi's Sarcoma-associated Herpesvirus ORF57
  • Nuclear Import
  • Nucleoporin Nup62
  • KSHV
  • Nucleocytoplasmic Transport

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