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Journal of Virology, October 1998, p. 7785-7795, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The NH2 Terminus of the Herpes Simplex Virus Type 1 Regulatory Protein ICP0 Contains a Promoter-Specific Transcription Activation Domain

Erik K. Lium, Christos A. Panagiotidis, Xiaoshan Wen, and Saul J. Silverstein*

Department of Microbiology and College of Physicians and Surgeons, Columbia University, New York, New York 10032

Received 9 April 1998/Accepted 15 June 1998

The transcriptional program of herpes simplex virus is regulated by the concerted action of three immediate-early (alpha ) proteins, ICP4, ICP27, and ICP0. The experiments described in this study examine the role of the acidic amino terminus (amino acids 1 to 103) of ICP0 in gene activation. When tethered to a DNA binding domain, this sequence activates transcription in the yeast Saccharomyces cerevisiae. Deletion of these amino acids affects the ability of ICP0 to activate alpha -gene promoter reporters in transient expression assays, while it has little or no effect on a beta - and a gamma -gene reporter in the same assay. Viruses that express the deleted form of ICP0 (ICP0-NX) have a small-plaque phenotype on both Vero cells and the complementing cell line L7. Transient expression and immunofluorescence analyses demonstrate that ICP0-NX is a dominant negative form of ICP0. Immunoprecipitation of ICP0 from cells coinfected with viruses expressing ICP0-NX and ICP0 revealed that ICP0 oligomerizes in infected cells. These data, in conjunction with the finding that ICP0-N/X is dominant negative, provide both biochemical and genetic evidence that ICP0 functions as a multimer in infected cells.

* Corresponding author. Mailing address: Department of Microbiology and College of Physicians and Surgeons, Columbia University, New York, NY 10032. Phone: (212) 305-8149. Fax: (212) 305-5106. E-mail: sjs6{at}columbia.edu.

Journal of Virology, October 1998, p. 7785-7795, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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