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Journal of Virology, May 2002, p. 4961-4970, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4961-4970.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Tegument Protein VP22 Contains Overlapping Domains for Cytoplasmic Localization, Microtubule Interaction, and Chromatin Binding

Ana Martin,1,{dagger} Peter O'Hare,2 John McLauchlan,3 and Gillian Elliott1*

Virus Assembly Group,1 Herpesvirus Group, Marie Curie Research Institute, Oxted, Surrey RH8 0TL,2 MRC Virology Unit, Institute of Virology, Glasgow G11 5JR, United Kingdom3

Received 11 December 2001/ Accepted 8 February 2002

We have previously shown that the 301-amino-acid herpes simplex virus tegument protein VP22 exhibits a range of subcellular localization patterns when expressed in isolation from other virus proteins. By using live-cell analysis of cells expressing green fluorescent protein (GFP)-tagged VP22 we have shown that when VP22 is first expressed in the cell it localizes to the cytoplasm, where, when present at high enough concentrations, it can assemble onto microtubules, causing them to bundle and become highly stabilized. In addition we have shown that when a cell expressing VP22 enters mitosis, the cytoplasmic population of VP22 translocates to the nucleus, where it efficiently binds mitotic chromatin. Here we have investigated the specific regions of the VP22 open reading frame required for these properties. Using GFP-VP22 as our starting molecule, we have constructed a range of N- and C-terminal truncations and analyzed their localization patterns in live cells. We show that the C-terminal 242 residues of VP22 are sufficient to induce microtubule bundling. Within this subregion, the C-terminal 89 residues contain a signal for cytoplasmic localization of the protein, while a larger region comprising the C-terminal 128 residues of the VP22 protein is required for mitotic chromatin binding. Furthermore, a central 100-residue domain of VP22 maintains the ability to bind microtubules without inducing bundling, suggesting that additional regions flanking this microtubule binding domain may be required to alter the microtubule network. Hence, the signals involved in dictating the complex localization patterns of VP22 are present in overlapping regions of the protein.

* Corresponding author. Mailing address: Virus Assembly Group, Marie Curie Research Institute, Oxted, Surrey RH8 0TL, United Kingdom. Phone: 01883 722306. Fax: 01883 714375. E-mail: g.elliott{at}mcri.ac.uk.

{dagger} Present address: GlaxoSmithKline, Greenford, Middlesex UB6 OHE, United Kingdom.

Journal of Virology, May 2002, p. 4961-4970, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4961-4970.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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