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Journal of Virology, April 2006, p. 4005-4016, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.4005-4016.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Products of the Herpes Simplex Virus Type 1 Immediate-Early US1/US1.5 Genes Downregulate Levels of S-Phase-Specific Cyclins and Facilitate Virus Replication in S-Phase Vero Cells

Joseph S. Orlando, Todd L. Astor, Scott A. Rundle, and Priscilla A. Schaffer*

Departments of Medicine and Microbiology and Molecular Genetics, Harvard Medical School at the Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215

Received 22 December 2005/ Accepted 2 February 2006

Herpes simplex virus type 1 ICP22–/US1.5– mutants initiate viral gene expression in all cells; however, in most cell types, the replication process stalls due to an inability to express {gamma}2 late proteins. Although the function of ICP22/US1.5 has not been established, it has been suggested that these proteins activate, induce, or repress the activity of cellular proteins during infection. In this study, we hypothesized that cell cycle-associated proteins are targets of ICP22/US1.5. For this purpose, we first isolated and characterized an ICP22–/US1.5– mutant virus, 22/n199. Like other ICP22–/US1.5– mutants, 22/n199 replicates in a cell-type-specific manner and fails to induce efficient {gamma}2 late gene expression in restrictive cells. Although synchronization of restrictive human embryonic lung cells in each phase of the cell cycle did not overcome the growth restrictions of 22/n199, synchronization of permissive Vero cells in S phase rendered them less able to support 22/n199 plaque formation and replication. Consistent with this finding, expression of cellular S-phase cyclins was altered in an ICP22/US1.5-dependent manner specifically when S-phase Vero cells were infected. Collectively, these observations support the notion that ICP22/US1.5 deregulates the cell cycle upon infection of S-phase permissive cells by altering expression of key cell cycle regulatory proteins either directly or indirectly.

* Corresponding author. Mailing address: Department of Medicine, Harvard Medical School at the Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN 123, Boston, MA 02215. Phone: (617) 667-2958. Fax: (617) 667-8540. E-mail: pschaffe{at}bidmc.harvard.edu.

Journal of Virology, April 2006, p. 4005-4016, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.4005-4016.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bastian, T. W., Rice, S. A. (2009). Identification of Sequences in Herpes Simplex Virus Type 1 ICP22 That Influence RNA Polymerase II Modification and Viral Late Gene Expression. J. Virol. 83: 128-139 [Abstract] [Full Text]  
  • Fraser, K. A., Rice, S. A. (2007). Herpes Simplex Virus Immediate-Early Protein ICP22 Triggers Loss of Serine 2-Phosphorylated RNA Polymerase II. J. Virol. 81: 5091-5101 [Abstract] [Full Text]  
  • Orlando, J. S., Balliet, J. W., Kushnir, A. S., Astor, T. L., Kosz-Vnenchak, M., Rice, S. A., Knipe, D. M., Schaffer, P. A. (2006). ICP22 Is Required for Wild-Type Composition and Infectivity of Herpes Simplex Virus Type 1 Virions. J. Virol. 80: 9381-9390 [Abstract] [Full Text]  


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