The low molecular weight heparan sulfate-mimetic, PI-88, inhibits cell-to-cell spread of herpes simplex virus

Nyberg, K., Ekblad, M., Bergström, T., Freeman, C., Parish, C.R., Ferro, V. and Trybal, E. (2004) The low molecular weight heparan sulfate-mimetic, PI-88, inhibits cell-to-cell spread of herpes simplex virus. Antiviral Research, 63 1: 15-24. doi:10.1016/j.antiviral.2004.01.001

Author Nyberg, K.
Ekblad, M.
Bergström, T.
Freeman, C.
Parish, C.R.
Ferro, V.
Trybal, E.
Title The low molecular weight heparan sulfate-mimetic, PI-88, inhibits cell-to-cell spread of herpes simplex virus
Journal name Antiviral Research   Check publisher's open access policy
ISSN 0166-3542
Publication date 2004-07
Sub-type Article (original research)
DOI 10.1016/j.antiviral.2004.01.001
Volume 63
Issue 1
Start page 15
End page 24
Total pages 10
Editor Earl R. Kern
Erik de Clerq
Richard J. Whitley
Place of publication Amsterdam, The Netherlands
Publisher Elsevier Science Publishers
Language eng
Subject 1108 Medical Microbiology
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Although a number of sulfated polysaccharides have been shown to inhibit infection of cells by herpes simplex virus (HSV), little is known about their effects on the cell-to-cell spread of the virus. These compounds act by inhibiting the virus binding to cells, and their antiviral potencies usually increase with increasing molecular weight and sulfation density. We report that the low molecular weight HS-mimetic, PI-88, which is a mixture of highly sulfated mannose-containing di- to hexa-saccharides, inhibited HSV infection of cells and cell-to-cell spread of HSV-1 and HSV-2. Compared to a relatively large heparin polysaccharide, PI-88 demonstrated weaker inhibition of HSV infectivity but more efficient reduction of cell-to-cell spread of HSV. A tetrasaccharide fraction of PI-88 was the minimum fragment necessary to inhibit HSV-1 infectivity, while a trisaccharide was sufficient to reduce cell-to-cell spread. A reduction in HSV lateral spread was also observed in cells incubated with another low molecular weight compound, pentosan polysulfate but not with much larger polysaccharide chondroitin sulfate E. Some differences as regards the effects of PI-88, heparin, protamine, poly-L-lysine and sodium chlorate on intercellular spread of HSV-1 and HSV-2 were found. We conclude that structurally different sulfated oligosaccharides are preferred for inhibition of HSV infectivity and the cell-to-cell spread. The latter was efficiently inhibited by a relatively small but densely sulfated PI-88 oligosaccharide, very likely due to the capability of the compound to access the narrow intercellular space.
© 2004 Elsevier B.V. All rights reserved.
Keyword Herpes simplex virus
Cell-to-cell spread
Heparan sulfate
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
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