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Now, let me examine the GO-CAM model in detail based on all the information gathered.

Review of GO-CAM Model: gomodel:62b4ffe300000067

Model Overview

Title: Poxvirus-OPG044 inhibition of interferon beta induction (Human-Poxvirus)
ID: gomodel:62b4ffe300000067
Taxon: Human (NCBITaxon:9606)
Status: Production

Model Structure

This model depicts the mechanism by which poxvirus protein OPG044 (K7) inhibits the induction of interferon beta by targeting DDX3X, preventing IRF3 activation. The model has 4 activities connected by causal relationships:

  1. DDX3X (O00571) - has "signaling adaptor activity" (GO:0035591)
  2. IKBKE/IKKε (Q14164) - has "protein serine/threonine kinase activity" (GO:0004674)
  3. IRF3 (Q14653-5) - has "DNA-binding transcription activator activity" (GO:0001216)
  4. Poxvirus OPG044/K7 (P68466) - has "protein sequestering activity" (GO:0140311)

The causal relationships are: - Poxvirus OPG044 negatively regulates DDX3X via direct sequestration - DDX3X positively regulates IKBKE - IKBKE positively regulates IRF3

Scientific Evaluation

1. Functional Accuracy

The model correctly represents the scientific understanding of how poxvirus K7 protein inhibits interferon production:

  • DDX3X as an adaptor protein: DDX3X functions as a signaling adaptor in the interferon pathway, linking IKBKE to IRF3. The model correctly annotates this with GO:0035591 (signaling adaptor activity).

  • IKBKE/IKKε role: IKBKE correctly functions as a protein kinase (GO:0004674) that phosphorylates IRF3, which is required for IRF3 activation.

  • IRF3 function: IRF3, when activated, functions as a transcription activator (GO:0001216) that induces interferon beta production.

  • Viral inhibitory mechanism: Vaccinia virus protein K7 is correctly shown inhibiting this pathway through sequestration of DDX3X (GO:0140311), preventing DDX3X from coupling IKBKE to IRF3.

2. Evidence Support

The model includes appropriate evidence codes and references:

  • All activities are supported by ECO:0000314 (direct assay evidence used in manual assertion)
  • Key references include PMID:18636090, PMID:23478265, and PMID:12692549
  • The contributor ORCID (0000-0001-7646-0052) is consistently provided

3. Structural Assessment

The model follows GO-CAM best practices for structural representation:

  • The causal relationships use appropriate relation ontology terms:
  • RO:0002630 (directly negatively regulates) for K7 inhibition of DDX3X

  • RO:0002629 (directly positively regulates) for positive regulatory relationships

  • The model includes appropriate subcellular locations:

  • DDX3X and IKBKE in cytoplasm (GO:0005737)

  • IRF3 in nucleus (GO:0005634)

  • The model correctly represents the involvement in the biological process of positive regulation of type I interferon production (GO:0032481)

4. Improvements/Recommendations

  1. Additional molecular details: The model could be enhanced by explicitly representing the phosphorylation of IRF3 at Ser-386 and Ser-396, which are key for IRF3 activation.

  2. Mechanistic refinement: The model could better represent the specific domains involved in the interaction between K7 and DDX3X (K7 binds to residues 71-90 of DDX3X).

  3. Biological context: The model appropriately represents the viral mechanism of immune evasion, but could be expanded to show downstream effects on interferon beta gene expression.

Conclusion

The GO-CAM model gomodel:62b4ffe300000067 accurately represents the scientific understanding of how vaccinia virus K7 protein inhibits interferon production by targeting DDX3X. The model follows GO-CAM best practices with appropriate activities, causal relationships, cellular locations, and supporting evidence.

The model effectively shows how viruses can target host signaling pathways to evade immune responses, specifically how poxvirus protein K7 disrupts the DDX3X-IKBKE-IRF3 pathway that leads to interferon production. This representation aligns with the published literature on DDX3X's role in innate immune signaling and viral evasion strategies.

Overall, this is a well-constructed GO-CAM model that meets quality standards for representing biological mechanisms in the context of host-pathogen interactions.