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Journal of Virology, March 2000, p. 2278-2287, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Extracellular Domain of Herpes Simplex Virus gE
Is Sufficient for Accumulation at Cell Junctions but Not for
Cell-to-Cell Spread
Todd
Wisner,1
Craig
Brunetti,2,
Kevin
Dingwell,1,
and
David C.
Johnson1,*
Department of Molecular Microbiology and
Immunology, Oregon Health Sciences University, Portland, Oregon
97201,1 and Department of Pathology,
McMaster University, Hamilton, Ontario, Canada L8N
3Z52
Received 20 September 1999/Accepted 18 November 1999
Herpes simplex virus (HSV) expresses a number of membrane
glycoproteins, including gB, gD, and gH/gL, that function in both entry
of virus particles and movement of virus from an infected cell to an
uninfected cell (cell-to-cell spread). However, a complex of HSV
glycoproteins gE and gI (gE/gI) is required for efficient cell-to-cell
spread, especially between cells that form extensive cell junctions,
yet it is not necessary for entry of extracellular virions. We
previously showed that gE/gI has the capacity to localize specifically
to cell junctions; the glycoprotein complex was found at lateral
surfaces of cells in contact with other cells but not at those lateral
surfaces not forming junctions or at apical surfaces. By virtue of
these properties, gE/gI is an important molecular handle on the poorly
understood process of cell-to-cell spread. Here, we show that the
cytoplasmic domain of gE is important for the proper delivery of gE/gI
to lateral surfaces of cells. Without this domain, gE/gI is found on
the apical surface of epithelial cells, and more uniformly in the
cytoplasm, although incorporation into the virion envelope is
unaffected. However, even without proper trafficking signals, a
substantial fraction of gE/gI retained the capacity to accumulate at
cell junctions. Therefore, the extracellular domain of gE can mediate
accumulation of gE/gI at cell junctions, if the glycoprotein can be
delivered there, probably through interactions with ligands on the
opposing cell. The role of phosphorylation of the cytoplasmic domain of
gE was also studied. A second mutant HSV type 1 was constructed in
which three serine residues that form a casein kinase II
phosphorylation site were changed to alanine residues, reducing
phosphorylation by 70 to 80%. This mutation did not affect
accumulation at cell junctions or cell-to-cell spread.
*
Corresponding author. Mailing address: Department of
Molecular Microbiology and Immunology, Oregon Health Sciences
University, 3181 SW Sam Jackson Park Rd., Mail code L220, Portland, OR
97201-3098. Phone: (503) 494-0834. Fax: (503) 494-6862. E-mail:
johnsoda{at}ohsu.edu.

Present address: Howard Hughes Medical Institute, University of
Wisconsin, Madison, WI
53706.

Present address: Department of Anatomy, University of Cambridge,
Cambridge, United
Kingdom.
Journal of Virology, March 2000, p. 2278-2287, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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