| Summary: | 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.
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