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Journal of Virology, January 2009, p. 200-209, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.00645-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Varicella-Zoster Virus Immediate-Early 63 Protein Interacts with Human Antisilencing Function 1 Protein and Alters Its Ability To Bind Histones H3.1 and H3.3{triangledown}

Aruna P. Ambagala,1,{dagger} Trent Bosma,1,{ddagger} Mir A. Ali,1 Maxim Poustovoitov,2,§ Jason J. Chen,3 Michael D. Gershon,3 Peter D. Adams,2 and Jeffrey I. Cohen1*

Laboratory of Clinical Infectious Diseases, Building 10, Room 11N234, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892,1 Department of Basic Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111,2 Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 100323

Received 21 March 2008/ Accepted 10 October 2008

Varicella-zoster virus (VZV) immediate-early 63 protein (IE63) is abundantly expressed during both acute infection in vitro and latent infection in human ganglia. Using the yeast two-hybrid system, we found that VZV IE63 interacts with human antisilencing function 1 protein (ASF1). ASF1 is a nucleosome assembly factor which is a member of the H3/H4 family of histone chaperones. IE63 coimmunoprecipitated and colocalized with ASF1 in transfected cells expressing IE63 and in VZV-infected cells. IE63 also colocalized with ASF1 in both lytic and latently VZV-infected enteric neurons. ASF1 exists in two isoforms, ASF1a and ASF1b, in mammalian cells. IE63 preferentially bound to ASF1a, and the amino-terminal 30 amino acids of ASF1a were critical for its interaction with IE63. VZV IE63 amino acids 171 to 208 and putative phosphorylation sites of IE63, both of which are critical for virus replication and latency in rodents, were important for the interaction of IE63 with ASF1. Finally, we found that IE63 increased the binding of ASF1 to histone H3.1 and H3.3, which suggests that IE63 may help to regulate levels of histones in virus-infected cells. Since ASF1 mediates eviction and deposition of histones during transcription, the interaction of VZV IE63 with ASF1 may help to regulate transcription of viral or cellular genes during lytic and/or latent infection.


* Corresponding author. Mailing address: Laboratory of Clinical Infectious Diseases, National Institutes of Health, 10 Center Dr., Building 10, Room 11N234, Bethesda, MD 20892. Phone: (301) 496-5265. Fax: (301) 496-7383. E-mail: jcohen{at}niaid.nih.gov

{triangledown} Published ahead of print on 29 October 2008.

{dagger} Present address: Division of Clinical Sciences, 1 King's College Circle, Room 6360, Medical Sciences Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

{ddagger} Present address: LabPLUS, P.O. Box 110031, Auckland City Hospital, Auckland, New Zealand.

§ Present address: Department of Molecular Genetics/NE20, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.


Journal of Virology, January 2009, p. 200-209, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.00645-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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