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J Virol, February 1998, p. 1235-1243, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Virus-Induced Cell Motility
Christopher M.
Sanderson,1
Michael
Way,2 and
Geoffrey L.
Smith1,*
Sir William Dunn School of Pathology,
University of Oxford, Oxford OX1 3RE, United
Kingdom,1 and
European Molecular
Biology Laboratory, Heidelberg D69117, Germany2
Received 11 September 1997/Accepted 4 November 1997
Many viruses induce profound changes in cell metabolism and
function. Here we show that vaccinia virus induces two distinct forms
of cell movement. Virus-induced cell migration was demonstrated by an
in vitro wound healing assay in which infected cells migrated independently into the wound area while uninfected cells remained relatively static. Time-lapse microscopy showed that the maximal rate
of migration occurred between 9 and 12 h postinfection.
Virus-induced cell migration was inhibited by preinactivation of viral
particles with trioxsalen and UV light or by the addition of
cycloheximide but not by addition of cytosine arabinoside or rifampin.
The expression of early viral genes is therefore necessary and
sufficient to induce cell migration. Following migration, infected
cells developed projections up to 160 µm in length which had
growth-cone-like structures and were frequently branched. Time-lapse
video microscopy showed that these projections were formed by extension
and condensation of lamellipodia from the cell body. Formation of
extensions was dependent on late gene expression but not the production
of intracellular enveloped (IEV) particles. The requirements for
virus-induced cell migration and for the formation of extensions
therefore differ from each other and are distinct from the
polymerization of actin tails on IEV particles. These data show that
poxviruses encode genes which control different aspects of cell
motility and thus represent a useful model system to study and dissect
cell movement.
*
Corresponding author. Mailing address: Sir William Dunn
School of Pathology, University of Oxford, South Parks Rd., Oxford OX1
3RE, United Kingdom. Phone: 44-1865-275521. Fax: 44-1865-275501. E-mail: glsmith{at}molbiol.ox.ac.uk.
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