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Journal of Virology, October 1999, p. 8843-8847, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Transactivation of Herpes Simplex Virus Type 1 Immediate-Early
Gene Expression by Virion-Associated Factors Is Blocked by an
Inhibitor of Cyclin-Dependent Protein Kinases
Robert
Jordan,*
Luis
Schang, and
Priscilla A.
Schaffer
Department of Microbiology, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Received 7 April 1999/Accepted 25 June 1999
Initiation of productive infection by human herpes simplex virus
type 1 (HSV-1) requires cell cycle-dependent protein kinase (cdk)
activity. Treatment of cells with inhibitors of cdks blocks HSV-1
replication and prevents accumulation of viral transcripts, including
immediate-early (IE) transcripts (26). Inhibition of IE
transcript accumulation suggests that virion proteins, such as VP16,
require functional cdks to activate viral transcription. In this
report, we show that a cdk inhibitor, Roscovitine, blocks VP16-dependent IE gene expression. In the presence of Roscovitine, the
level of virion-induced activation of a transfected reporter gene (the
gene encoding chloramphenicol acetyltransferase) linked to the
promoter-regulatory region of the ICP0 gene was reduced 40-fold
relative to that of untreated samples. Roscovitine had little effect on
the interaction of VP16 with VP16-responsive DNA sequences as measured
by electrophoretic mobility shift assays. These data indicate that
VP16-dependent activation of IE gene expression requires functional
cdks and that this requirement is independent of the ability of VP16 to
bind to DNA.
*
Corresponding author. Present address: Department of
Biochemistry and Molecular Pharmacology, The Jefferson Center for
Biomedical Research, 700 Butler Ave., Doylestown, PA 18901-2697. Phone:
(215) 489-4914. Fax: (215) 489-4920. E-mail:
Robert.Jordan{at}mail.tju.edu.
Journal of Virology, October 1999, p. 8843-8847, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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