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Journal of Virology, April 2006, p. 3650-3654, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3650-3654.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Impact of the Interaction between Herpes Simplex Virus Type 1 Regulatory Protein ICP0 and Ubiquitin-Specific Protease USP7 on Activation of Adeno-Associated Virus Type 2 rep Gene Expression

Marie-Claude Geoffroy,1 Gilliane Chadeuf,1 Anne Orr,2 Anna Salvetti,1 and Roger D. Everett2*

INSERM U649, CHU Hotel-Dieu, Nantes, France,1 MRC Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom2

Received 26 October 2005/ Accepted 18 January 2006

Expression of the herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 in transfected cells reactivates rep gene expression from integrated adeno-associated virus (AAV) type 2 genomes via a mechanism that requires both its RING finger and USP7 interaction domains. In this study, we found that the rep reactivation defect of USP7-binding-negative ICP0 mutants can be overcome by further deletion of sequences in the C-terminal domain of ICP0, indicating that binding of USP7 to ICP0 is not directly required. Unlike the case in transfected cells, only the RING finger domain of ICP0 was essential for rep gene reactivation during HSV-1 infection. However, mutants unable to bind to USP7 activate HSV-1 gene expression and reactivate rep gene expression with reduced efficiencies. These results further elucidate the role of ICP0 as a helper factor for AAV replication and illustrate that care is required when extrapolating from the properties of ICP0 in transfection assays to events occurring during HSV-1 infection.

* Corresponding author. Mailing address: MRC Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom. Phone: 44 141 330 3923. Fax: 44 141 330 3521. E-mail: r.everett{at}vir.gla.ac.uk.

Journal of Virology, April 2006, p. 3650-3654, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3650-3654.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Everett, R. D., Parsy, M.-L., Orr, A. (2009). Analysis of the Functions of Herpes Simplex Virus Type 1 Regulatory Protein ICP0 That Are Critical for Lytic Infection and Derepression of Quiescent Viral Genomes. J. Virol. 83: 4963-4977 [Abstract] [Full Text]  
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