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Journal of Virology, November 2009, p. 11502-11513, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01318-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Histone Deacetylases 1 and 2 Are Phosphorylated at Novel Sites during Varicella-Zoster Virus Infection{triangledown}

Matthew S. Walters,1 Angela Erazo,2,3 Paul R. Kinchington,2 and Saul Silverstein1*

Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, New York 10032,1 Departments of Ophthalmology and of Molecular Microbiology and Genetics,2 Graduate Program in Molecular Virology and Microbiology, University of Pittsburgh, 203 Lothrop St., Pittsburgh, Pennsylvania 152133

Received 26 June 2009/ Accepted 2 September 2009

ORF66p, a virion-associated varicella-zoster virus (VZV) protein, is a member of a conserved Alphaherpesvirinae kinase family with homology to herpes simplex virus US3 kinase. Expression of ORF66p in cells infected with VZV or an adenovirus expressing only ORF66p results in hyperphosphorylation of histone deacetylase 1 (HDAC1) and HDAC2. Mapping studies reveal that phosphorylation is at a unique conserved Ser residue in the C terminus of both HDACs. This modification requires an active kinase domain in ORF66p, as neither protein is phosphorylated in cells infected with VZV lacking kinase activity. However, hyperphosphorylation appears to occur indirectly, as within the context of in vitro kinase reactions, purified ORF66p phosphorylates a peptide derived from ORF62p, a known substrate, but does not phosphorylate HDAC. These results support a model where ORF66p is necessary but not sufficient to effect hyperphosphorylation of HDAC1 and HDAC2.


* Corresponding author. Mailing address: Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-8149. Fax: (212) 305-5106. E-mail: sjs6{at}columbia.edu

{triangledown} Published ahead of print on 9 September 2009.


Journal of Virology, November 2009, p. 11502-11513, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01318-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.