Herpes Simplex Virus Initiates the Intrinsic Pathway of Coagulation.
Bibliographic record
Abstract
Abstract Abstract 3173 Poster Board III-113 A hemostatic response to vascular injury is initiated by the extrinsic pathway of coagulation and amplified by the intrinsic pathway. We previously reported that purified herpes simplex virus type-1 (HSV1) has constitutive extrinsic pathway tissue factor (TF) and anionic phospholipid on its surface derived from the host cell, and can consequently bypass strict cellular control of coagulation. The current work addresses the hypothesis that HSV1-induced plasma coagulation also involves intrinsic pathway, factor VIII (FVIII), and upstream contact activation pathway, factor XII (FXII). HSV1-initiated clotting was accelerated when purified FVIII was added to FVIII-deficient plasma. The involvement of FVIII was confirmed by an inhibitory anti-FVIII antibody (Ab), which attenuated HSV1-initiated clotting of normal plasma. High HSV1 concentrations predictably reduced the effect of FVIII due to the availability of excess viral TF. To further define clotting mechanisms initiated by HSV1, the extrinsic pathway was disabled using factor VII-deficient plasma. The intrinsic pathway may be triggered by contact activation of FXII by kallikrein when bound to a suitable surface. Here we found that an inhibitor of activated FXII, corn trypsin inhibitor, and anti-FXII Ab attenuated HSV1-initiated clotting. Direct activation of purified FXII by the virus was not observed. Supporting the involvement of kallikrein in FXII activation due to HSV1, anti-kallikrein Ab was also inhibitory. The current work shows that HSV1 can trigger and amplify coagulation through the intrinsic and contact activation pathways, and suggests an additional mechanism that may explain prior reports linking virus infection to vascular pathology. Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".