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Journal of Virology, April 1999, p. 2803-2813, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Herpes Simplex Virus Type 1 Regulatory Protein ICP27 Is Required for the Prevention of Apoptosis in Infected Human Cells

Martine Aubert and John A. Blaho*

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029

Received 10 November 1998/Accepted 23 December 1998

The herpes simplex virus type 1 (HSV-1) ICP27 protein is an immediate-early or alpha  protein which is essential for the optimal expression of late genes as well as the synthesis of viral DNA in cultures of Vero cells. Our specific goal was to characterize the replication of a virus incapable of synthesizing ICP27 in cultured human cells. We found that infection with an HSV-1 ICP27 deletion virus of at least three separate strains of human cells did not produce immediate-early or late proteins at the levels observed following wild-type virus infections. Cell morphology, chromatin condensation, and genomic DNA fragmentation measurements demonstrated that the human cells died by apoptosis after infection with the ICP27 deletion virus. These features of the apoptosis were identical to those which occur during wild-type infections of human cells when total protein synthesis has been inhibited. Vero cells infected with the ICP27 deletion virus did not exhibit any of the features of apoptosis. Based on these results, we conclude that while HSV-1 infection likely induced apoptosis in all cells, viral evasion of the response differed among the cells tested in this study.


* Corresponding author. Mailing address: Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Pl., New York, NY 10029. Phone: (212) 241-7318. Fax: (212) 534-1684. E-mail: blaho{at}msvax.mssm.edu.


Journal of Virology, April 1999, p. 2803-2813, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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  • Jerome, K. R., Fox, R., Chen, Z., Sears, A. E., Lee, H.-y., Corey, L. (1999). Herpes Simplex Virus Inhibits Apoptosis through the Action of Two Genes, Us5 and Us3. J. Virol. 73: 8950-8957 [Abstract] [Full Text]  
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