Factor Xa and Factor VIIa Utilize Herpes Simplex Virus-Associated Tissue Factor to Increase Infection through Cellular Protease Activated Receptor 2.
Bibliographic record
Abstract
Abstract Abstract 2130 Poster Board II-107 We have shown previously that purified herpes simplex type-1 (HSV1) can initiate coagulation on its surface because of tissue factor (TF) derived from the host cell and virus-encoded glycoprotein C (gC). Generation of thrombin by this viral surface pathway correlated to an increase in the susceptibility of cells to infection through a mechanism involving protease activated receptor (PAR) 1. Incomplete inhibition of the serum-mediated increase in infection by hirudin indicated that mechanisms in addition to thrombin are involved. To further investigate the importance of coagulation enzymes in HSV1 infection, the current study investigated the upstream activated coagulation factors X (FXa) and VII (FVIIa). Using a novel panel of viruses deficient in either TF and/or gC in cytolytic viral plaque assays, we examined the contribution of viral TF and gC in the FXa- or FVIIa- mediated infection of human umbilical vein endothelial cells. The addition of purified FXa resulted in up to 400% enhancement of infection when TF and gC were on the virus surface. Similarly, the effect of FVIIa was maximal when TF and gC were present, although only 150% increased. In agreement with previous studies, the addition of purified thrombin resulted in approximately a 500% increase in infection using the novel panel of viruses, which unlike FXa and FVIIa was not dependent on either viral TF or gC. Simultaneous addition of FXa/FVIIa or thrombin/FXa/FVIIa further enhanced infection to a maximum of 10-fold. FX alone had no effect on infection; however, in situ FXa generation due to the addition of FVIIa increased infection. The involvement of PAR2 was shown using inhibitory PAR2 specific antibodies which attenuated the effects of FXa and FVIIa. Anti-PAR1 inhibited the effect of thrombin, but had no effect on either FXa- or FVIIa-dependent infection. The importance of viral TF was demonstrated by inhibition of FXa or FVIIa-mediated plaque formation by anti-TF antibody, which had an insignificant effect on TF-deficient HSV1. Collectively, these data indicate that FXa and FVIIa together with TF on the virus surface may activate cellular PAR2 to increase HSV1 infection independent of thrombin. Disclosures: Ruf: Pfizer: Research Funding; Novo Nordisk: Research Funding.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".