Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells.

Herpesviral infection of endothelial cells (ECs) induces arterial injury. We now demonstrate that such infection promoted enhanced monocyte-endothelial adhesion. Enhanced adhesion was blocked by monoclonal antibodies to the viral-encoded cell surface glycoprotein gC but not by antibodies to gD or gE. Adhesion was also blocked by treating ECs with specific thrombin inhibitors or by growing cells in prothrombin-depleted serum. We found that gC bound and promoted activation of factor X on infected ECs, thereby contributing to thrombin generation. Factor X also bound to transfected L cells that were induced to express gC. Cross-linking and immunoprecipitation studies demonstrated factor X-gC complex formation on the surface of these cells. We suggest that gC-dependent thrombin generation by herpes-infected endothelium may be an important mediator of vascular pathology during viral infection.