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Journal of Virology, March 2000, p. 2131-2141, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Cytoplasm-to-Nucleus Translocation of a Herpesvirus
Tegument Protein during Cell Division
Gillian
Elliott1,* and
Peter
O'Hare2
Virus Assembly Group1
and Herpesvirus Group,2 Marie Curie
Research Institute, The Chart, Oxted, Surrey RH8 0TL, United
Kingdom
Received 15 November 1999/Accepted 13 December 1999
We have previously shown that the herpes simplex virus tegument
protein VP22 localizes predominantly to the cytoplasm of expressing cells. We have also shown that VP22 has the unusual property of intercellular spread, which involves the movement of VP22 from the
cytoplasm of these expressing cells into the nuclei of nonexpressing cells. Thus, VP22 can localize in two distinct subcellular patterns. By
utilizing time-lapse confocal microscopy of live cells expressing a
green fluorescent protein-tagged protein, we now report in detail the
intracellular trafficking properties of VP22 in expressing cells, as
opposed to the intercellular trafficking of VP22 between expressing and
nonexpressing cells. Our results show that during interphase VP22
appears to be targeted exclusively to the cytoplasm of the expressing
cell. However, at the early stages of mitosis VP22 translocates from
the cytoplasm to the nucleus, where it immediately binds to the
condensing cellular chromatin and remains bound there through all
stages of mitosis and chromatin decondensation into the G1
stage of the next cycle. Hence, in VP22-expressing cells the
subcellular localization of the protein is regulated by the cell cycle
such that initially cytoplasmic protein becomes nuclear during cell
division, resulting in a gradual increase over time in the number of
nuclear VP22-expressing cells. Importantly, we demonstrate that this
process is a feature not only of VP22 expressed in isolation but also
of VP22 expressed during virus infection. Thus, VP22 utilizes an
unusual pathway for nuclear targeting in cells expressing the protein
which differs from the nuclear targeting pathway used during
intercellular trafficking.
*
Corresponding author. Mailing address: Virus Assembly
Group, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom. Phone: 01883 722306. Fax: 01883 714375. E-mail: g.elliott{at}mcri.ac.uk.
Journal of Virology, March 2000, p. 2131-2141, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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