The role of glycosaminoglycans in binding of herpes simplex virus type 1 to mammalian cells
Autor: | Leduc, Yves |
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Jazyk: | angličtina |
Rok vydání: | 1993 |
Druh dokumentu: | Text |
Popis: | Binding of herpes simplex virus type 1 (HSV-1) to the cell surfaces initially requires interactions between viral glycoproteins embedded in the viral envelope and cell surface glycosaminoglycans (GAGs). In this work, mutant cells derived from Ltk⁻ murine fibroblasts and devoid of the cell surface GAG heparan sulfate (HS) (gro2C cells) or HS and chondroitin sulfate (CS) (sog9 cells) were used to study the importance of these GAGs in HSV-1 binding. HSV-1 plaque formation and binding, as assessed by the use of radiolabeled virions, were reduced by approximately 85% with gro2C cells relative to parental L cells. This indicated that cell surface HS is important but not essential for HSV-1 binding. Addition of soluble forms of HS and, to a lesser extent, CS types A, B (both 4-sulfated), and C (6- sulfated) blocked adsorption of HSV-1 to gro2C cells and thereby inhibited plaque formation in a GAG concentration dependent manner. The high efficiency by which HS inhibited HSV-1 plaquing on gro2C cells relative to L cells indicated that HSV-1 binding to gro2C cells was "weaker" than to L cells. The inhibitory effect of CS type B on HSV-1 plaquing to gro2C cells showed that HSV-1 can interact with CS, albeit less efficiently than with HS, and suggested that HSV-1 binding to gro2C cells might involve cell surface CS. Further indications for the role of cell surface CS in HSV-1 binding came from the use of the gro2C derived, HS- and CS-deficient sog9 cells. Associated with this phenotype was a reduction in HSV-1 plaquing: 1% relative to L cells which suggests that cell surface CS is responsible for HSV-1 binding to CS-containing gro2C cells. These results indicate a predominant role for cell surface HS in HSV-1 binding and a secondary role for cell surface CS. Additional results obtained from studying the effects of synthetic anionic polysaccharides (dextran sulfate, DEAEdextran, and dextran T-500) on HSV-1 plaquing with L, gro2C and sog9 cells suggest that the HSV-1 interactions with GAGs are electrostatic in nature with minor requirements for the recognition of structural features. Science, Faculty of Microbiology and Immunology, Department of Graduate |
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