Ultraviolet‐inactivated human cytomegalovirus induces placental syncytiotrophoblast apoptosis in a Toll‐like receptor‐2 and tumour necrosis factor‐α dependent manner
Bibliographic record
Abstract
Placentae obtained from newborns with congenital human cytomegalovirus (HCMV) infection often display chronic villitis and disruptions of the syncytiotrophoblast (ST). Little is known about how HCMV infection induces inflammation in the villous placenta and loss of the trophoblast. We propose that the inflammation is initiated with innate defence responses of the ST to maternal blood-borne virus. In this paper we show with a culture model (ST derived from primary cytotrophoblasts) that UV-inactivated HCMV (UV-HCMV) doubled the frequency of ST apoptosis. ST cultures challenged with UV-HCMV increased transcription and secretion of the inflammatory cytokines tumour necrosis factor alpha (TNFalpha) and interleukin-8, and antibody to TNFalpha inhibited UV-HCMV-induced apoptosis. Treatment with cycloheximide, an inhibitor of protein translation, did not reduce UV-HCMV-induced TNFalpha gene transcription, indicating that upregulation was independent of de novo protein synthesis. Neutralizing antibody to Toll-like receptor (TLR)2 inhibited UV-HCMV-induced transcription and translation of TNFalpha, and consequently inhibited the increase in ST apoptosis. Our results show that even transcriptionally inactive HCMV binding to TLR2 on ST can initiate inflammation, including secretion of TNFalpha, which leads to trophoblast death.
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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) | 0.001 | 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 | 0.001 |
| 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".