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Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through Nup62, inhibiting host nucleocytoplasmic transport pathways
Authors:Malik Poonam  Tabarraei Alijan  Kehlenbach Ralph H  Korfali Nadia  Iwasawa Ryota  Graham Sheila V  Schirmer Eric C
Institution:Wellcome 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
Abstract: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.
Keywords: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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