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Journal of Virology, December 2006, p. 11589-11597, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01869-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Evidence that the Immediate-Early Gene Product ICP4 Is Necessary for the Genome of the Herpes Simplex Virus Type 1 ICP4 Deletion Mutant Strain d120 To Circularize in Infected Cells{triangledown}

Ying-Hsiu Su,1* Xianchao Zhang,1 Xiaohe Wang,1 Nigel W. Fraser,2 and Timothy M. Block1

Drexel Institute for Biotechnology and Virology Research and Department of Microbiology and Immunology, College of Medicine, Drexel University, 3805 Old Easton Road, Doylestown, Pennsylvania 18901-2697,1 Department of Microbiology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104-60762

Received 28 August 2006/ Accepted 11 September 2006

Following infection, the physical state of linear herpes simplex virus (HSV) genomes may change into an "endless" or circular form. In this study, using Southern blot analysis of the HSV genome, we provide evidence that immediate-early protein ICP4 is involved in the process of converting the linear HSV-1 ICP4-deleted mutant strain d120 genome into its endless form. Under conditions where de novo viral DNA synthesis was inhibited, the genome of the ICP4 deletion mutant d120 failed to assume an endless conformation following infection of Vero cells (compared with the ability of wild-type strain KOS). This defect was reversed in the Vero-derived cell line E5, which produces the ICP4 protein, suggesting that ICP4 is necessary and sufficient to complement the d120 defect. When ICP4 protein was provided by the replication-defective DNA polymerase mutant HP66, the genomes of mutant d120 could assume an endless conformation in Vero cells. Western blot analysis using antibody specific to the ICP4 protein showed that although the d120 virions contained ICP4 protein, the majority of that ICP4 protein was in a 40-kDa truncated form, with only a small fraction present as a full-length 175-kDa protein. When expression of ICP4 protein from E5 cells was inhibited by cycloheximide, the d120 virion-associated ICP4 protein was unable to mediate endless formation after infection of E5 cells. Collectively, these data suggest that ICP4 protein has an important role in mediating the endless formation of the HSV-1 genome upon infection and that this function can be provided in trans.

* Corresponding author. Mailing address: Rm 250, Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Drexel University, 3805 Old Easton Road, Doylestown, PA 18901-2697. Phone: (215) 489-4907. Fax: (215) 489-4920. E-mail: ys98{at}drexel.edu.

{triangledown} Published ahead of print on 20 September 2006.

Journal of Virology, December 2006, p. 11589-11597, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01869-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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