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Journal of Virology, November 2007, p. 11781-11789, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01234-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Reactivation of Expression from Quiescent Herpes Simplex Virus Type 1 Genomes in the Absence of Immediate-Early Protein ICP0{triangledown}

Chris M. Preston*

Medical Research Council Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom

Received 6 June 2007/ Accepted 10 August 2007

Model systems have previously been developed in which herpes simplex virus (HSV) is retained in human fibroblasts in a nonreplicating state known as quiescence. The HSV type 1 (HSV-1) immediate-early (IE) protein ICP0, an important activator of gene expression, reactivates the quiescent genome and promotes the resumption of virus replication. Previous studies reported that infection with ICP0-null HSV-1 mutants fails to reactivate quiescent HSV, even when the mutant itself undergoes productive replication, leading to the hypothesis that quiescent genomes exist in a silent configuration in which they are shielded from trans-acting factors. I reinvestigated these findings, using HSV-1 mutants with lesions in the transcription activators VP16, ICP0, and ICP4 to establish quiescent infection at high efficiency. Superinfection with ICP0-null HSV-1 mutants at a low multiplicity of infection (MOI), so that individual plaques were formed, reactivated expression from the quiescent genome, demonstrating that the requirement for ICP0 is not absolute. The previously reported failure to observe reactivation by ICP0-null mutants was shown to be a consequence of either a low initial MOI or a high superinfecting MOI. Competition between viral genomes at the level of gene expression and virus replication, especially when ICP0 was absent, was demonstrated during reactivation and also during normal infection of human fibroblasts. The results show that the multiplicity-dependent phenotype of ICP0-null mutants limits the efficiency of reactivation at low MOIs and that competition between genomes occurs at high MOIs. The conclusion that quiescent HSV genomes are extensively silenced and intrinsically insensitive to trans-acting factors must be reevaluated.

* Mailing address: Medical Research Council Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom. Phone: 44 141 330 3921. Fax: 44 141 330 3520. E-mail: c.preston{at}mrcvu.gla.ac.uk

{triangledown} Published ahead of print on 22 August 2007.

Journal of Virology, November 2007, p. 11781-11789, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01234-07
Copyright © 2007, 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]  
  • Tang, S., Patel, A., Krause, P. R. (2009). Novel Less-Abundant Viral MicroRNAs Encoded by Herpes Simplex Virus 2 Latency-Associated Transcript and Their Roles in Regulating ICP34.5 and ICP0 mRNAs. J. Virol. 83: 1433-1442 [Abstract] [Full Text]  
  • Saira, K., Chowdhury, S., Gaudreault, N., da Silva, L., Henderson, G., Doster, A., Jones, C. (2008). The Zinc RING Finger of Bovine Herpesvirus 1-Encoded bICP0 Protein Is Crucial for Viral Replication and Virulence. J. Virol. 82: 12060-12068 [Abstract] [Full Text]  
  • Preston, C. M., Nicholl, M. J. (2008). Induction of Cellular Stress Overcomes the Requirement of Herpes Simplex Virus Type 1 for Immediate-Early Protein ICP0 and Reactivates Expression from Quiescent Viral Genomes. J. Virol. 82: 11775-11783 [Abstract] [Full Text]  
  • McMahon, R., Walsh, D. (2008). Efficient Quiescent Infection of Normal Human Diploid Fibroblasts with Wild-Type Herpes Simplex Virus Type 1. J. Virol. 82: 10218-10230 [Abstract] [Full Text]  


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