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Thromb Haemost 2004; 92(05): 947-955
DOI: 10.1160/TH04-04-0242
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Herpes simplex virus type 1-encoded glycoprotein C enhances coagulation factor VIIa activity on the virus

Michael R. Sutherland
1   Canadian Blood Services, Research and Development Department; University of Ottawa, Department of Biochemistry, Microbiology and Immunology, Ottawa, Ontario, Canada; University of British Columbia, Centre for Blood Research, Department of Pathology and Laboratory Medicine,Vancouver, British Columbia, Canada
,
Harvey M. Friedman
2   Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
,
Edward L. G. Pryzdial
1   Canadian Blood Services, Research and Development Department; University of Ottawa, Department of Biochemistry, Microbiology and Immunology, Ottawa, Ontario, Canada; University of British Columbia, Centre for Blood Research, Department of Pathology and Laboratory Medicine,Vancouver, British Columbia, Canada
› Author AffiliationsFinancial support: This work was supported by grants from the Canadian Institutes of Health Research and Heart and Stroke Foundation of British Columbia/Yukon (EP), National Institutes of Health grant HL 28220 (HF) and a Canadian Blood Services Graduate Scholarship (MS).
Further Information

Publication History

Received 16 April 2004

Accepted after revision 03 September 2004

Publication Date:
04 December 2017 (online)

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Summary

Tissue factor (TF) is the blood coagulation initiator, whose cofactor function is required for physiological factor VIIa (FVIIa)-mediated activation of factor X (FX) to FXa. A previous study reported TF on herpes simplex virus type 1 (HSV1), but this explained only part of FVIIa-dependent FXa generation observed on the virus surface (Sutherland et al. (1997) Proc. Natl. Acad. Sci. USA. 94:13510-14). In the current study, we investigated the role of HSV1-encoded glycoprotein C (gC) in this process. Purified gC-deficient HSV1 facilitated several fold less FX activation by FVIIa than either wild type or gC-rescued strains.To confirm the implication of gC in FVIIa-dependent FX activation, purified soluble gC (sgC) enhanced FXa production in the absence of TF. sgC required FVIIa, calcium and anionic phospholipid to participate in FX activation, suggesting similarity to TF. When purified virus was combined with sgC, the sgC-dependent FXa generation was enhanced three orders of magnitude, suggesting synergy with an additional HSV1 component and explaining the relatively low activity of purified sgC compared to the viral counterpart. FX activation on gC-competent HSV1 was inhibited 20% by a gC-specific antibody, inhibited 40% by a TF-specific antibody, inhibited 65% by combining the gCand TF-specific antibodies, and nearly completely inhibited by the TF antibody alone on gC-deficient HSV-1. Cumulatively, these observations show that two pathways initiating FX activation function in parallel on the virus surface. In addition to the previously described TF-dependent pathway, HSV-1-encoded gC also enhances FXa generation, and like TF, requires FVIIa.

Keywords

Tissue factor - factor VII - factor X - glycoprotein C - herpes simplex virus
 

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