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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Raynor, C. M. Wright, J. F. Sutherland, M. R. Leenknegt, H. Pryzdial, E. L. |
| Description | Author Affiliation: Sutherland MR ( The Canadian Red Cross Society, Research and Development Department, 1800 Alta Vista Drive, and Department of Biochemistry, University of Ottawa, Ottawa, ON Canada K1G 4J5.); |
| Abstract | Herpesviruses have been previously correlated to vascular disease and shown to cause thrombogenic and atherogenic changes to host cells. Herein we show that even in the absence of cells, purified cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can initiate thrombin production. Functional assays demonstrated that purified HSV-1 and HSV-2 provide the necessary phospholipid (proPL) for assembling the coagulation factors Xa and Va into prothrombinase, which is responsible for generating thrombin. These observations are consistent with our earlier studies involving CMV. The presence of proPL on all three herpesviruses was confirmed directly by flow cytometry and electron microscopy by using annexin V and factor Va, respectively, as proPL-specific probes. Of equal importance, we found that CMV, HSV-1, and HSV-2 were also able to facilitate factor Xa generation from the inactive precursor factor X, but only when factor VII/VIIa and Ca2+ were present. Monoclonal antibodies specific for tissue factor (TF), the coagulation initiator, inhibited this factor X activation and, furthermore, enabled identification of TF antigen on each virus type by flow cytometry and electron microscopy. Collectively, these data show that CMV, HSV-1, and HSV-2 can initiate the generation of thrombin by having essential proPL and TF activities on their surface. Unlike the normal cellular source, the viral activity is constitutive and, therefore, not restricted to sites of vascular injury. Thus cell-independent thrombin production may be the earliest event in vascular pathology mediated by herpesviruses. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 94 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1997-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Blood Coagulation Physiology Herpesviridae Pathogenicity Vascular Diseases Etiology Blood Coagulation Factors Metabolism Cytomegalovirus Factor X Herpesvirus 1, Human Herpesvirus 2, Human In Vitro Techniques Phospholipids Thrombin Biosynthesis Thrombosis Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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