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Journal of Virology, December 2008, p. 12030-12038, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01575-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus ICP0 Promotes both Histone Removal and Acetylation on Viral DNA during Lytic Infection{triangledown}

Anna R. Cliffe and David M. Knipe*

Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115

Received 24 July 2008/ Accepted 30 September 2008

During lytic infection, the genome of herpes simplex virus 1 (HSV-1) is associated with limited levels of histones but does not form a regular repeating nucleosomal structure. However, the previous observation that chromatin remodeling factors are recruited into viral replication compartments indicates that chromatin remodeling plays a role in HSV-1 gene expression and DNA replication. In this study we demonstrate the presence of histone H3 on HSV-1 DNA early in infection at levels equivalent to those found on a cellular gene. The proportion of viral DNA associated with histone H3 decreases at later times postinfection, independently of either viral DNA replication or transcription. We demonstrate that an immediate-early protein, infected cell protein 0 (ICP0), is required for both a reduction in the proportion of HSV-1 DNA associating with histone H3 and an increase in histone acetylation. This study provides evidence that ICP0 directly alters the chromatin structure of the HSV-1 genome during lytic infection, and this system will serve as a useful model for the reduction of histone load in higher eukaryotes.

* Corresponding author. Mailing address: Harvard Medical School, Department of Microbiology and Molecular Genetics, 200 Longwood Avenue, Boston, MA 02115. Phone: (617) 432-1934. Fax: (617) 432-0223. E-mail: david_knipe{at}hms.harvard.edu

{triangledown} Published ahead of print on 8 October 2008.

Journal of Virology, December 2008, p. 12030-12038, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01575-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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