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Journal of Virology, November 1999, p. 9456-9467, Vol. 73, No. 11
MRC Virology Unit, Glasgow G11 5JR, Scotland,
United Kingdom
Received 30 April 1999/Accepted 17 July 1999
Herpes simplex virus type 1 (HSV-1) immediate-early protein Vmw110
stimulates the onset of virus infection in a multiplicity-dependent manner and is required for efficient reactivation from latency. Recent
work has shown that Vmw110 is able to interact with or modify the
stability of several cellular proteins. In this report we analyze the
ability of Vmw110 to inhibit the progression of cells through the cell
cycle. We show by fluorescence-activated cell sorter and/or confocal
microscopy analysis that an enhanced green fluorescent protein-tagged
Vmw110 possesses the abilities both to prevent transfected cells moving
from G1 into S phase and to block infected cells at an
unusual stage of mitosis defined as pseudo-prometaphase. The latter
property correlates with the Vmw110-induced proteasome-dependent
degradation of CENP-C, a centromeric protein component of the inner
plate of human kinetochores. We also show that whereas Vmw110 is not
the only viral product implicated in the block of infected cells at the
G1/S border, the mitotic block is a specific property of
Vmw110 and more particularly of its RING finger domain. These data
explain the toxicity of Vmw110 when expressed alone in transfected
cells and provide an explanation for the remaining toxicity of
replication-defective mutants of HSV-1 expressing Vmw110. In addition
to contributing to our understanding of the effects of Vmw110 on the
cell, our results demonstrate that Vmw110 expression is incompatible
with the proliferation of a dividing cell population. This factor is of
obvious importance to the design of gene therapy vectors based on
HSV-1.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Herpes Simplex Virus Type 1 Immediate-Early Protein
Vmw110 Inhibits Progression of Cells through Mitosis and from
G1 into S Phase of the Cell Cycle
*
Corresponding author. Mailing address: MRC Virology
Unit, Institute of Virology, Church St., Glasgow G11 5JR, Scotland,
United Kingdom. Phone: 44 0 141 330 6299. Fax: 44 0 141 337 2236. E-mail: p.lomonte{at}vir.gla.ac.uk.
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