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

Malik, P., Tabarraei, A., Kehlenbach, R. H., Korfali, N., Iwasawa, R., Graham, S. and Schirmer, E. C. (2012) Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through NUP62, inhibiting host nucleocytoplasmic transport pathways. Journal of Biological Chemistry, 287(15), pp. 12277-12292. (doi: 10.1074/jbc.M111.331777)

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 wildtype 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.

• Item Type: Articles
• Additional Information: This research was originally published in Journal of Biological Chemistry. Malik, P., Tabarraei, A., Kehlenbach, R., Korfali, N., Iwasawa, R., Graham, S. and Schirmer, E. 'Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through NUP62, inhibiting host nucleocytoplasmic transport pathways'. Journal of Biological Chemistry. 2012. Vol:287 (15), 12277-12292. © the American Society for Biochemistry and Molecular Biology
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Graham, Professor Sheila and Tabarraei, Mr Alijan
• Authors: Malik, P., Tabarraei, A., Kehlenbach, R. H., Korfali, N., Iwasawa, R., Graham, S., and Schirmer, E. C.
• Subjects: Q Science > QR Microbiology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J.Biol. Chem.
• Publisher: American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258
• ISSN (Online): 1083-351X
• Copyright Holders: Copyright © 2012 American Society for Biochemistry and Molecular Biology
• First Published: First published in Journal of Biological Chemistry 287(15):12277-12292
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

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Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
38031	1	A family of multifunctional proteins that orchestrates RNA metabolism in herpesvirus infected cells	Sheila Graham	Medical Research Council (MRC)	G9826324	Centre for Virus Research