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PMID: 7745699 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission.

Journal of virology ·Vol. 69 ·No. 6 ·1995-06-00 ·Pages 3517-28

Brunetti CR, Burke RL, Hoflack B, Ludwig T, Dingwell KS, Johnson DC

Abstract

Herpes simplex virus (HSV) glycoprotein D (gD) is essential for virus entry into cells, is modified with mannose-6-phosphate (M-6-P), and binds to both the 275-kDa M-6-P receptor (MPR) and the 46-kDa MPR (C. R. Brunetti, R. L. Burke, S. Kornfeld, W. Gregory, K. S. Dingwell, F. Masiarz, and D. C. Johnson, J. Biol. Chem. 269:17067-17074, 1994). Since MPRs are found on the surfaces of mammalian cells, we tested the hypothesis that MPRs could serve as receptors for HSV during virus entry into cells. A soluble form of the 275-kDa MPR, derived from fetal bovine serum, inhibited HSV plaques on monkey Vero cells, as did polyclonal rabbit anti-MPR antibodies. In addition, the number and size of HSV plaques were reduced when cells were treated with bovine serum albumin conjugated with pentamannose-phosphate (PM-PO4-BSA), a bulky ligand which can serve as a high-affinity ligand for MPRs. These data imply that HSV can use MPRs to enter cells; however, other molecules must also serve as receptors for HSV because a reasonable fraction of virus could enter cells treated with even the highest concentrations of these inhibitors. Consistent with the possibility that there are other receptors, HSV produced the same number of plaques on MPR-deficient mouse fibroblasts as were produced on normal mouse fibroblasts, but there was no inhibition with PM-PO4-BSA with either of these embryonic mouse cells. Together, these results demonstrate that HSV does not rely solely on MPRs to enter cells, although MPRs apparently play some role in virus entry into some cell types and, perhaps, act as one of a number of cell surface molecules that can facilitate entry. We also found that HSV produced small plaques on human fibroblasts derived from patients with pseudo-Hurler's polydystrophy, cells in which glycoproteins are not modified with M-6-P residues and yet production of infectious HSV particles was not altered in the pseudo-Hurler cells. In addition, HSV plaque size was reduced by PM-PO4-BSA; therefore, it appears that M-6-P residues and MPRs are required for efficient transmission of HSV between cells, a process which differs in some respects from entry of exogenous virus particles.

MeSH Terms
Animals Cell Line Chlorocebus aethiops Fibroblasts/virology Humans Membrane Fusion Mice Phosphorylation Receptor, IGF Type 2/physiology Simplexvirus/physiology Vero Cells Viral Plaque Assay
Chemicals
Receptor, IGF Type 2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Brunetti C R
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Burke R L
Hoflack B
Ludwig T
Dingwell K S
Johnson D C
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1995-06-00
Pages
3517-28
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC189065
Subset
IM
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