Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through Nup62, inhibiting host

Poonam Malik1, Alijan Tabarraei, Ralph H Kehlenbach

  • 1Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, Scotland, United Kingdom. p.malik@ed.ac.uk

Insights

Herpes simplex virus ICP27 protein binds Nup62, a nuclear pore component. This interaction influences viral mRNA export and host cell nuclear import pathways.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • The herpes simplex virus ICP27 protein is crucial for viral gene expression and mRNA nuclear export.
  • While ICP27's interactions with RNA and host transport factors like TAP are known, its direct interaction with the nuclear pore complex (NPC) is not fully understood.

Purpose of the Study:

  • To investigate the direct interaction between the herpes simplex virus ICP27 protein and the nuclear pore complex.
  • To elucidate the role of ICP27's interaction with nucleoporins in viral nuclear export and host nuclear transport.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • In vitro binding assays using purified proteins.
  • Analysis of ICP27 deletion and point mutants to map interaction domains.

Main Results:

  • ICP27 directly binds to Nup62, a core nucleoporin of the nuclear pore complex.
  • The interaction between ICP27 and Nup62 requires sequences in both the N- and C-termini of ICP27.
  • Wild-type ICP27 expression inhibits importin α/β- and transportin-dependent nuclear import, while an Nup62-binding deficient mutant does not.

Conclusions:

  • ICP27's association with Nup62 facilitates its own nuclear transport and viral mRNA export.
  • ICP27 may inhibit host cell nuclear import by competing with host transport receptors for binding to NPCs.

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