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Journal of Virology, January 2001, p. 1013-1030, Vol. 75, No. 2
Department of Microbiology, Mount Sinai
School of Medicine, New York, New York 10029,1
and Department of Microbiology, University of Minnesota Medical
School, Minneapolis, Minnesota 554552
Received 29 August 2000/Accepted 23 October 2000
We previously reported that a recombinant ICP27-null virus
stimulated, but did not prevent, apoptosis in human HEp-2 cells during
infection (M. Aubert and J. A. Blaho, J. Virol. 73:2803-2813, 1999). In the present study, we used a panel of 15 recombinant ICP27 mutant viruses to determine which features of herpes simplex virus type 1 (HSV-1) replication are required for the
apoptosis-inhibitory activity. Each virus was defined experimentally as
either apoptotic, partially apoptotic, or nonapoptotic based on
infected HEp-2 cell morphologies, percentages of infected cells with
condensed chromatin, and patterns of specific cellular death factor
processing. Viruses d27-1, d1-5,
d1-2, M11, M15, M16, n504R,
n406R, n263R, and n59R are
apoptotic or partially apoptotic in HEp-2 cells and severely defective
for growth in Vero cells. Viruses d2-3,
d3-4, d4-5, d5-6, and
d6-7 are nonapoptotic, demonstrating that ICP27 contains a large amino-terminal region, including its RGG box RNA binding domain, which is not essential for apoptosis prevention. Accumulations of viral TK, VP16, and gD but not gC, ICP22, or ICP4 proteins correlated with prevention of apoptosis during the replication of these
viruses. Of the nonapoptotic viruses, d4-5 did not
produce gC, indicating that accumulation of true late gene products is not necessary for the prevention process. Analyses of viral DNA synthesis in HEp-2 cells indicated that apoptosis prevention by HSV-1
requires that the infection proceeds to the stage in which viral DNA
replication takes place. Infections performed in the presence of the
drug phosphonoacetic acid confirmed that the process of viral DNA
synthesis and the accumulation of true late (
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.1013-1030.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Accumulation of Herpes Simplex Virus Type 1 Early and
Leaky-Late Proteins Correlates with Apoptosis Prevention in
Infected Human HEp-2 Cells
2) proteins
are not required for apoptosis prevention. Based on our results, we
conclude that the accumulation of HSV-1 early (
) and leaky-late
(
1) proteins correlates with the prevention of apoptosis
in infected HEp-2 cells.
*
Corresponding author. Mailing address: Department of
Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy
Place, New York, NY 10029. Phone: (212) 241-7318. Fax: (212) 534-1684. E-mail: john.blaho{at}mssm.edu.
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