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

C. R. Brunetti, R. L. Burke, B. Hoflack, T. Ludwig, K. S. Dingwell, David Johnson

Research output: Contribution to journalArticle

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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 rule 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.

Original languageEnglish (US)
Pages (from-to)3517-3528
Number of pages12
JournalJournal of Virology
Volume69
Issue number6
StatePublished - 1995
Externally publishedYes

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IGF Type 2 Receptor
herpes simplex
Virus Internalization
Simplexvirus
mannose
phosphates
viruses
receptors
cells
Fibroblasts
fibroblasts
Virion
Glycoproteins
virion
Mucolipidoses
glycoproteins
Ligands
mice
Vero Cells
Bovine Serum Albumin

ASJC Scopus subject areas

  • Immunology

Cite this

Brunetti, C. R., Burke, R. L., Hoflack, B., Ludwig, T., Dingwell, K. S., & Johnson, D. (1995). Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission. Journal of Virology, 69(6), 3517-3528.

Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission. / Brunetti, C. R.; Burke, R. L.; Hoflack, B.; Ludwig, T.; Dingwell, K. S.; Johnson, David.

In: Journal of Virology, Vol. 69, No. 6, 1995, p. 3517-3528.

Research output: Contribution to journalArticle

Brunetti, CR, Burke, RL, Hoflack, B, Ludwig, T, Dingwell, KS & Johnson, D 1995, '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, pp. 3517-3528.
Brunetti, C. R. ; Burke, R. L. ; Hoflack, B. ; Ludwig, T. ; Dingwell, K. S. ; Johnson, David. / Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission. In: Journal of Virology. 1995 ; Vol. 69, No. 6. pp. 3517-3528.
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