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Herpes simplex virus type 1-encoded glycoprotein C contributes to direct coagulation factor X-virus binding
Joel R Livingston1, Michael R Sutherland, Harvey M Friedman
1Canadian Blood Services, Research and Development Department, University of British Columbia/Centre for Blood Research, Department of Pathology and Laboratory Medicine, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
The Biochemical Journal
|October 11, 2005
Summary
Herpes simplex virus type 1 (HSV1) directly binds Factor X (FX) via its glycoprotein C (gC), initiating blood coagulation. This interaction may explain links between HSV1 infections and vascular disease.
Area of Science:
- Virology
- Hematology
- Molecular Biology
Background:
- Herpes simplex virus type 1 (HSV1) initiates blood coagulation through Factor VIIa (FVIIa)-dependent activation of Factor X (FX).
- Direct interactions between FX and HSV1 are suggested by the roles of tissue factor and viral glycoprotein C (gC) in enhancing FVIIa function.
Purpose of the Study:
- To investigate the direct binding interactions between Factor X (FX) and purified herpes simplex virus type 1 (HSV1).
- To elucidate the specific role of viral glycoprotein C (gC) in mediating FX-HSV1 interactions and subsequent blood coagulation.
Main Methods:
- Utilized differential sedimentation to quantify the binding of radiolabeled FX to purified wild-type and gC-deficient HSV1.
- Determined binding kinetics, including apparent dissociation constants (K(d)) and the number of binding sites per virus.
- Assessed the binding of soluble recombinant gC (sgC) to HSV1 and its effect on FX-HSV1 interactions.
Main Results:
- Factor X (FX) binds directly to wild-type HSV1 in a calcium-dependent manner, with a K(d) of 1.5 μM and 206 binding sites per virus.
- Glycoprotein C (gC) is a primary binding site for FX on HSV1, as gC-deficient virus showed significantly reduced FX binding.
- Soluble gC (sgC) binds HSV1 and inhibits FX-virus association, suggesting a Ca2+-independent interaction in solution.
Conclusions:
- Glycoprotein C (gC) mediates a direct interaction between HSV1 and Factor X (FX), contributing to virus-initiated blood coagulation.
- These findings provide a molecular basis for the observed clinical correlations between recurrent HSV1 infections and vascular pathology.