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Journal of Virology, April 2003, p. 4315-4325, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4315-4325.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

CK2 Protein Kinase Is Stimulated and Redistributed by Functional Herpes Simplex Virus ICP27 Protein

Maria D. Koffa,1,{dagger} Joy Kean,1 George Zachos,2 Stephen A. Rice,3 and J. Barklie Clements1*

Institute of Virology, University of Glasgow, Glasgow G11 5JR,1 Beatson Laboratories, University of Glasgow, Glasgow G61 1QH, Scotland, United Kingdom,2 Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 554553

Received 26 September 2002/ Accepted 6 January 2003

It has been shown previously (S. Wadd, H. Bryant, O. Filhol, J. E. Scott, T.-T. Hsieh, R. D. Everett, and J. B. Clements, J. Biol. Chem. 274:28991-28998, 2000) that ICP27, an essential and multifunctional herpes simplex virus type 1 (HSV-1) protein, interacts with CK2 and with heterogeneous ribonucleoprotein K (hnRNP K). CK2 is a pleiotropic and ubiquitous protein kinase, and the tetrameric holoenzyme consists of two catalytic {alpha} or {alpha}' subunits and two regulatory ß subunits. We show here that HSV-1 infection stimulates CK2 activity. CK2 stimulation occurs at early times after infection and correlates with redistribution of the holoenzyme from the nucleus to the cytoplasm. Both CK2 stimulation and redistribution require expression and cytoplasmic accumulation of ICP27. In HSV-1-infected cells, CK2 phosphorylates ICP27 and affects its cytoplasmic accumulation while it also phosphorylates hnRNP K, which is not ordinarily phosphorylated by this kinase, suggesting an alteration of hnRNP K activities. This is the first example of CK2 stimulation by a viral protein in vivo, and we propose that it might facilitate the HSV-1 lytic cycle by, for example, regulating trafficking of ICP27 protein and/or viral RNAs.

* Corresponding author. Mailing address: Institute of Virology, University of Glasgow, Church St., Glasgow, G11 5JR Scotland, United Kingdom. Phone: 44-141-330-4027. Fax: 44-141-337-2236. E-mail: b.clements{at}vir.gla.ac.uk.

{dagger} Present address: Gene Expression Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.

Journal of Virology, April 2003, p. 4315-4325, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4315-4325.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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