The tegument protein VP22 of pseudorabies virus inhibits cGAS condensation by inducing nuclear-to-cytoplasmic translocation of DDX21
Bibliographic record
Abstract
Cyclic GMP-AMP synthase (cGAS) is a pivotal DNA sensor that initiates antiviral responses, yet the mechanisms by which viruses evade cGAS-mediated innate immunity remain poorly understood. Here, we identified VP22, a tegument protein of pseudorabies virus (PRV), a member of the Alphaherpesvirinae subfamily, as a viral antagonist of the type I interferon (IFN-I) response through hijacking the host RNA helicase DDX21. Specifically, VP22 impairs 2'3'-cyclic GMP-AMP (cGAMP) synthesis by disrupting cGAS condensation. In vivo, cGAS restricts the replication of VP22-deficient PRV and attenuates its pathogenicity, an effect neutralized by VP22. Notably, DDX21 is essential for VP22-mediated inhibition of cGAS activity. Mechanistically, VP22 stabilizes DDX21 protein level and enhances its interaction with cGAS. Furthermore, VP22 promotes the translocation of DDX21 from the nucleus to the cytoplasm, a process required for inhibition of cGAS condensation and activation. Collectively, these findings reveal a previously unrecognized, host-dependent mechanism by which PRV subverts cGAS signaling, shedding light on viral strategies to subvert host DNA sensing and innate immunity.
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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".