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Coagulation initiated on herpesviruses
M R Sutherland1, C M Raynor, H Leenknegt
1The Canadian Red Cross Society, Research and Development Department, 1800 Alta Vista Drive, and Department of Biochemistry, University of Ottawa, Ottawa, ON Canada K1G 4J5.
Summary
Herpesviruses like CMV, HSV-1, and HSV-2 can independently trigger thrombin production by providing essential procoagulant phospholipids and tissue factor. This cell-independent viral activity may initiate vascular disease early on.
Area of Science:
- Virology
- Hematology
- Vascular Biology
Background:
- Herpesviruses are linked to vascular diseases, causing thrombotic and atherogenic changes.
- Previous studies suggested a role for cytomegalovirus (CMV) in these processes.
Purpose of the Study:
- To investigate if purified herpesviruses (CMV, HSV-1, HSV-2) can initiate thrombin production independently of host cells.
- To identify the mechanisms by which these viruses promote coagulation.
Main Methods:
- Functional coagulation assays were performed using purified viruses.
- Flow cytometry and electron microscopy were employed to detect viral surface components.
- Procoagulant phospholipid (proPL) and tissue factor (TF) presence and activity were assessed.
- Inhibition studies using monoclonal antibodies against TF were conducted.
Main Results:
- Purified CMV, HSV-1, and HSV-2 initiated thrombin production without host cells.
- HSV-1 and HSV-2 provided proPL for prothrombinase assembly, similar to CMV.
- All three viruses displayed TF activity, facilitating Factor X activation in the presence of Factor VII/VIIa and Ca2+.
- TF antigen was identified on the viral surfaces.
Conclusions:
- CMV, HSV-1, and HSV-2 possess proPL and TF activities on their surfaces, enabling cell-independent thrombin generation.
- This constitutive viral procoagulant activity, not limited to injury sites, may represent an early mechanism in herpesvirus-mediated vascular pathology.