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Journal of Virology, August 1999, p. 6769-6781, Vol. 73, No. 8
Department of Microbiology, Mount Sinai
School of Medicine, New York, New York 10029
Received 10 February 1999/Accepted 21 April 1999
The UL49 gene product (VP22) of herpes simplex virus
types 1 and 2 (HSV-1 and HSV-2) is a virion phosphoprotein which
accumulates inside infected cells at late stages of infection. We
previously (J. A. Blaho, C. Mitchell, and B. Roizman, J. Biol. Chem. 269:17401-17410, 1994) discovered that the form of VP22
packaged into infectious virions differed from VP22 extracted from
infected-cell nuclei in that the virion-associated form had a higher
electrophoretic mobility in denaturing gels. Based on these results, we
proposed that VP22 in virions was "undermodified" in some way. The
goal of this study is to document the biological and biochemical
properties of VP22 throughout the entire course of a productive HSV-1
infection. We now report the following. (i) VP22 found in infected
cells is distributed in at least three distinct subcellular
localizations, which we define as cytoplasmic, diffuse, and nuclear, as
measured by indirect immunofluorescence. (ii) Using a synchronized
infection system, we determined that VP22 exists predominantly in the
cytoplasm early in infection and accumulates in the nucleus late in
infection. (iii) While cytoplasmic VP22 colocalizes with the HSV-1
glycoprotein D early in infection, the nuclear form of VP22 is not
restricted to replication compartments which accumulate ICP4. (iv) VP22
migrates as at least three unique electrophoretic species in denaturing sodium dodecyl sulfate-DATD-polyacrylamide gels. VP22a, VP22b, and
VP22c have high, intermediate, and low mobility, respectively. (v) The
relative distribution of the various forms of VP22 derived from
infected whole-cell extracts varies during the course of infection such
that low-mobility species predominate at early times and high-mobility
forms accumulate later. (vi) The highest-mobility forms of VP22
partition with the cytoplasmic fraction of infected cells, while the
lowest-mobility forms are associated with the nuclear fraction. (vii)
Finally, full-length VP22 which partitions in the nucleus incorporates
radiolabel from [32P]orthophosphate whereas cytoplasmic
VP22 does not. Based on these results, we conclude that modification of
VP22 coincides with its appearance in the nucleus during the course of
productive HSV-1 infection.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Modified VP22 Localizes to the Cell Nucleus during
Synchronized Herpes Simplex Virus Type 1 Infection
*
Corresponding author. Mailing address: Department of
Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy
Place, New York, NY 10029-6574. Phone: (212) 241-7319. Fax: (212)
534-1684. E-mail: blaho{at}msvax.mssm.edu.
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