Molecular interactions regulating RIG‐I signaling to the innate antiviral response
Bibliographic record
Abstract
Cytosolic sensing of incoming RNA virus infection is recognized by the DExD/H box RNA helicases RIG‐I and Mda5. The mitochondrial adaptor MAVS links sensing of viral RNA by RIG‐I/Mda5 to downstream signaling, resulting in the induction of pro‐inflammatory and antiviral genes by NF‐ κB and IRF respectively. We have demonstrated that NEMO, the adaptor of the IKK complex, induces activation of IRF3/7, acting downstream of RIG‐I and MAVS but upstream of TBK1/IKKε. NEMO requires TANK adaptor to mediate recruitment of the kinases and phosphorylation of IRF3/7. Thus, NEMO bridges the NF‐κB and IRF components of RIG‐I with the formation of a multimeric kinase complex. Ubiquitination plays a central role in regulating the activity of the RIG‐I pathway. MAVS undergoes K63 ubiquitination at a single Ser500 residue, adjacent to the MAVS transmembrane domain and a TRAF interacting motif (TIM). K63‐linked ubiquitination of MAVS mediates recruitment of IKKε, but not TBK1, to the mitochondrial compartment. Recruitment of TRAF3 to the C‐terminal TIM motif of MAVS is sterically hindered by IKKε, but is relieved by mutation of K500. Interestingly, the MAVS K500R mutant did not affect IFN gene activation, but rather appears to alter processing of NF‐κB2p100 in the non‐canonical NF‐κB pathway. Thus, MAVS ubiquitination provides another level at which to regulate the RIG‐I response to virus infection. This research was supported by grants from CIHR and NCIC.
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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) | 0.004 | 0.002 |
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".