Ankyrin Repeat Domain 22 Mediates Host Defense Against Viral Infection Through STING Signaling Pathway
Bibliographic record
Abstract
Abstract The innate immune system is critical for early detection of invading viruses and for initiating cellular host defense countermeasures, which include the production of interferons. Ankyrin repeat domain 22 (ANKRD22) encodes a protein of 191 amino acids containing 2 ankyrin repeating domain, and its biological function was unknown. In this study, we find that ANKRD22 expression can be significantly induced in human peripheral blood mononuclear cells (PBMCs) by DNA virus herpes simplex virus -1(HSV-1) and RNA virus respiratory syncytial virus (RSV) as well as IFN-α and IFN-γ. Its induction in PBMCs by viruses is largely a secondary effect of virus-induced interferons. We further demonstrate that ANKRD22 was majorly induced in monocytes and dendritic cells from PBMCs. Over-expression of ANKRD22 confers protection against HSV-1 and RSV infection in multiple tested cell lines. Vice versa, inhibition of ANKRD22 leads to enhanced HSV-1 and RSV replication in host cells. Furthermore, we identifies that ANKRD22 specifically interacts with STING, a critical protein function in multiple antiviral innate immune pathways. ANKRD22 by itself can only slightly induce type I IFNs IFN-α and IFN-β, and can’t induce type III IFN IL-29. However, it significantly synergizes STING-induced both type I and type III interferon production. Collectively, our studies indicate that ANKRD22 plays an important role for host defense against both DNA and RNA viruses by optimizing STING’s function on inducing type I and type III IFNs.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".