Herpes simplex virus type 1-encoded glycoprotein C contributes to direct coagulation factor X-virus binding.

The HSV1 (herpes simplex virus type 1) surface has been shown recently to initiate blood coagulation by FVIIa (activated Factor VII)-dependent proteolytic activation of FX (Factor X). At least two types of direct FX-HSV1 interactions were suggested by observing that host cell-encoded tissue factor and virus-encoded gC (glycoprotein C) independently enhance FVIIa function on the virus. Using differential sedimentation to separate bound from free 125I-ligand, we report in the present study that, in the presence of Ca2+, FX binds directly to purified wild-type HSV1 with an apparent dissociation constant (K(d)) of 1.5+/-0.4 muM and 206+/-24 sites per virus at saturation. The number of FX-binding sites on gC-deficient virus was reduced to 43+/-5, and the remaining binding had a lower K(d) (0.7+/-0.2 microM), demonstrating an involvement of gC. Engineering gC back into the deficient strain or addition of a truncated soluble recombinant form of gC (sgC), increased the K(d) and the number of binding sites. Consistent with a gC/FX stoichiometry of approximately 1:1, 121+/-6 125I-sgC molecules were found to bind per wild-type HSV1. In the absence of Ca2+, the number of FX-binding sites on the wild-type virus was similar to the gC-deficient strain in the presence of Ca2+. Furthermore, in the absence of Ca2+, direct sgC binding to HSV1 was insignificant, although sgC was observed to inhibit the FX-virus association, suggesting a Ca2+-independent solution-phase FX-sgC interaction. Cumulatively, these data demonstrate that gC constitutes one type of direct FX-HSV1 interaction, possibly providing a molecular basis for clinical correlations between recurrent infection and vascular pathology.