Herpes simplex virus type 1-encoded glycoprotein C enhances coagulation factor VIIa activity on the virus.
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 gC- and 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.
Sutherland
Michael R
MR
Canadian Blood Services, Research and Development Department, Canada.
Friedman
Harvey M
HM
Pryzdial
Edward L G
EL
D015942:Factor VIIa / Q000187:drug effects* / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa / Q000096:biosynthesis / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D013917:Thrombin / Q000096:biosynthesis / Q000187:drug effects; D013925:Thromboplastin / Q000502:physiology; D014652:Vascular Diseases / Q000821:virology; D014759:Viral Envelope Proteins / Q000302:isolation & purification / Q000494:pharmacology*
D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; D005170:Factor X; D013925:Thromboplastin; D015942:Factor VIIa; D013917:Thrombin; D015951:Factor Xa