The 4EHP-mediated translational repression of cGAS impedes the host immune response against DNA viruses
Bibliographic record
Abstract
A critical host response against viral infections entails the activation of innate immune signaling that culminates in the production of antiviral proteins. DNA viruses are sensed by the cytosolic pattern recognition receptor cyclic GMP–AMP synthase (cGAS), which initiates a signaling pathway that results in production of proinflammatory cytokines such as Interferon-β (IFN-β) and activation of the antiviral response. Precise regulation of the antiviral innate immune response is required to avoid deleterious effects of its overactivation. We previously reported that the 4EHP/GIGYF2 translational repressor complex reduces the translation of Ifnb1 mRNA, which encodes IFN-β, upon RNA viral infections. Here, we report a distinct regulatory mechanism by which 4EHP controls replication of DNA viruses by translational repression of the Cgas mRNA, which encodes the DNA viral sensor cGAS. We show that 4EHP is required for effective translational repression of Cgas mRNA triggered by miR-23a. Upon infection, 4EHP deficiency bolsters the elicited innate immune response against the diverse DNA viruses Herpes simplex virus 1 (HSV-1) and Vaccinia Virus (VacV) and concomitantly reduces their rate of replication in vitro and in vivo. This study elucidates an intrinsic regulatory mechanism of the host response to DNA viruses which may provide unique opportunities for countering viral infections.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".