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Journal of Virology, May 2007, p. 4429-4437, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02354-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Infection Induces Phosphorylation and Delocalization of Emerin, a Key Inner Nuclear Membrane Protein{triangledown}

James B. Morris, Helmut Hofemeister, and Peter O'Hare*

Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom

Received 27 October 2006/ Accepted 2 February 2007

The inner nuclear membrane (INM) contains specialized membrane proteins that selectively interact with nuclear components including the lamina, chromatin, and DNA. Alterations in the organization of and interactions with INM and lamina components are likely to play important roles in herpesvirus replication and, in particular, exit from the nucleus. Emerin, a member of the LEM domain class of INM proteins, binds a number of nuclear components including lamins, the DNA-bridging protein BAF, and F-actin and is thought to be involved in maintaining nuclear integrity. Here we report that emerin is quantitatively modified during herpes simplex virus (HSV) infection. Modification begins early in infection, involves multiple steps, and is reversed by phosphatase treatment. Emerin phosphorylation during infection involves one or more cellular kinases but can also be influenced by the US3 viral kinase, a protein whose function is known to be involved in HSV nuclear egress. The results from biochemical extraction analyses and from immunofluorescence of the detergent-resistant population demonstrate that emerin association with the INM significantly reduced during infection. We propose that the induction of emerin phosphorylation in infected cells may be involved in nuclear egress and uncoupling interactions with targets such as the lamina, chromatin, or cytoskeletal components.

* Corresponding author. Mailing address: MCRI, The Chart, Oxted, Surrey RH8 0TL, United Kingdom. Phone: 44 1883 722 306. Fax: 44 1883 714 375. E-mail: p.ohare{at}mcri.ac.uk

{triangledown} Published ahead of print on 14 February 2007.

Journal of Virology, May 2007, p. 4429-4437, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02354-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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