Bibliographic record
Abstract
Problem: There is growing interest in the role of viral infections and their association with adverse pregnancy outcomes.While the trophoblast is permissive to viruses, little is known about their impact on the placenta.We previously established that the Toll-like receptor 8 (TLR8) agonist, viral ssRNA, induces a pro-inflammatory cytokine response in first trimester trophoblast.Thus, we sought to determine the mechanisms involved, and whether viral ssRNA could induce an antiviral response. Methods of study:The human first trimester trophoblast cell line, HTR8, was stably transfected to express either a TLR8 dominant negative (DN) or MyD88-DN.The wildtype, TLR8-DN or MyD88-DN cells were treated with or without viral ssRNA (5 µg/mL).After 12 hr, RNA was extracted and qRT-PCR performed for pro-inflammatory cytokines [IL-8, IL-6]; type I interferons [IFNa, IFNb], antiviral factors [2 0 ,5 0 -oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G)]; and antimicrobial peptides [secretory leukocyte protease inhibitor (SLPI), human beta defensin-1 (HBD1) and HBD2].Results: Treatment of wildtype trophoblast with ssRNA significantly increased mRNA for IL-6 by 8.3fold; IL-8 by 1.3-fold; IFNa by 2.6-fold; IFNb by 3.6fold; OAS by 1.4-fold; MxA by 2.5-fold; APOBEC3G by 2.2-fold; and SLPI by 2.3-fold, compared to untreated controls (P < 0.05).ssRNA had no effect on HBD1/2 expression.The TLR8-DN significantly inhibited ssRNA-induced IL-6 by 70.1%; IL-8 by 61.7%; IFNa by 48.1%; and SLPI by 58.6%, compared to wildtype cells (P < 0.05).Similarly, the MyD88-DN significantly inhibited ssRNA-induced IL-6 by 69.4%; IL-8 by 70%; IFNa by 64.6%; and SLPI by 55.4%.Viral ssRNA-induced upregulation of IFNb, OAS, MxA and APOBEC3G was unaffected by either the TLR8-DN or MyD88-DN.Conclusions: These findings demonstrate that viral ssRNA induces a trophoblast inflammatory cytokine, IFNa, and SLPI response through TLR8 and MyD88.In contrast, the ssRNA-induced IFNb and subsequent antiviral response occurs independently of the TLR8/ MyD88 pathway.
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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 | 0.002 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.005 | 0.004 |
| Open science | 0.003 | 0.005 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.703 | 0.531 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".