title: Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells.
abstract: 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.
authors.affiliation: Department of Medicine, Cornell University Medical College, New York, New York 10021.
authors.forename: O R
authors.initials: OR
authors.lastname: Etingin
authors.forename: R L
authors.initials: RL
authors.lastname: Silverstein
authors.forename: H M
authors.initials: HM
authors.lastname: Friedman
authors.forename: D P
authors.initials: DP
authors.lastname: Hajjar
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000382:microbiology*; D005165:Factor V / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa; D006801:Humans; D009000:Monocytes / Q000502:physiology; D018139:Simplexvirus / Q000472:pathogenicity*; D013917:Thrombin / Q000096:biosynthesis*; D014759:Viral Envelope Proteins / Q000502:physiology
chemical_list: D014759:Viral Envelope Proteins; C048232:glycoprotein C, herpes simplex virus type 2; C022475:prothrombinase complex; D005165:Factor V; D005170:Factor X; D013917:Thrombin; D015951:Factor Xa