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Journal of Virology, October 2004, p. 10977-10986, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10977-10986.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Type 1 ICP0 Protein Mediates Activation of Adeno-Associated Virus Type 2 rep Gene Expression from a Latent Integrated Form

Marie-Claude Geoffroy,1 Alberto L. Epstein,2 Estelle Toublanc,1 Philippe Moullier,1 and Anna Salvetti1*

INSERM U649, CHU Hôtel-Dieu, Nantes,1 CNRS UMR 5534, Université Claude Bernard Lyon 1, Villeurbanne France2

Received 3 February 2004/ Accepted 15 June 2004

Adeno-associated virus type 2 (AAV-2) is a human parvovirus that requires the presence of a helper virus, such as the herpes simplex virus type 1 (HSV-1) to accomplish a complete productive cycle. In the absence of helper virus, AAV-2 can establish a latent infection that is characterized by the absence of expression of viral genes. So far, four HSV-1 early genes, UL5/8/52 (helicase primase complex) and UL29 (single-stranded DNA-binding protein), were defined as sufficient for AAV replication when cells were transfected with a plasmid carrying the wild-type AAV-2 genome. However, none of these viral products was shown to behave as a transcriptional factor able to activate AAV gene expression. Our study provides the first evidence that the immediate-early HSV-1 protein ICP0 can promote rep gene expression in cells latently infected with wild-type AAV-2. This ICP0-mediated effect occurs at the transcriptional level and involves the ubiquitin-proteasome pathway. Furthermore, using deletion mutants, we demonstrate that the localization of ICP0 to ND10 and their disruption is not required for the activation of the rep promoter, whereas binding of ICP0 to the ubiquitin-specific protease HAUSP makes a significant contribution to this effect.

* Corresponding author. Mailing address: INSERM U649, Laboratoire de Thérapie Génique, CHU Hôtel-Dieu, BÂt. Jean Monnet, 30 Bd Jean Monnet, 1, 44035 Nantes Cedex 01, France. Phone: 33 240087490. Fax: 33 240087491. E-mail: salvetti{at}sante.univ-nantes.fr.

Journal of Virology, October 2004, p. 10977-10986, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10977-10986.2004
Copyright © 2004, 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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