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Based on the information gathered, I'll now provide a detailed review of the GO-CAM model gomodel:62b4ffe300000717.

Review of GO-CAM Model: gomodel:62b4ffe300000717

Model Title

"Poxvirus-OPG025 inhibition of antiviral IFITs (Human-Poxvirus)"

Model Overview

This model represents how a Vaccinia virus protein (OPG025/C9L, UniProtKB:P17372) inhibits the antiviral activities of human IFIT proteins (IFIT1, IFIT2, IFIT3) by acting as a molecular adaptor that promotes the ubiquitin-dependent degradation of these proteins via the SCF (Skp, Cullin, F-box) ubiquitin ligase complex.

Model Components and Biological Pathway

The model consists of 6 activities:

  1. Vaccinia virus OPG025/C9L (UniProtKB:P17372) - Molecular adaptor activity (GO:0060090)
  2. Occurs in cytoplasm (GO:0005737)
  3. Part of symbiont-mediated suppression of host innate immune response (GO:0052170)

  4. Directly positively regulates CUL1 activity

  5. Human CUL1 (UniProtKB:Q13616) - Ubiquitin protein ligase binding (GO:0031625)

  6. Occurs in cytoplasm (GO:0005737)
  7. Part of SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146)

  8. Directly negatively regulates IFIT1, IFIT2, and IFIT3 activities

  9. Human IFIT1 (UniProtKB:P09914) - RNA binding (GO:0003723)

  10. Occurs in cytoplasm (GO:0005737)

  11. Part of antiviral innate immune response (GO:0140374)

  12. Human IFIT2 (UniProtKB:P09913) - RNA binding (GO:0003723)

  13. Occurs in cytoplasm (GO:0005737)

  14. Part of antiviral innate immune response (GO:0140374)

  15. Human IFIT3 (UniProtKB:O14879) - RNA binding (GO:0003723)

  16. Occurs in cytoplasm (GO:0005737)

  17. Part of antiviral innate immune response (GO:0140374)

  18. Human IFNB1 (UniProtKB:P01574) - Cytokine activity (GO:0005125)

  19. Occurs in extracellular space (GO:0005615)
  20. Part of type I interferon-mediated signaling pathway (GO:0060337)
  21. Causally upstream of, positive effect on IFIT1, IFIT2, and IFIT3 activities

Review Analysis

Consistency with GO-CAM Best Practices

  1. Molecular Adaptor Activity Representation:
  2. The model correctly uses molecular adaptor activity (GO:0060090) for the viral protein OPG025/C9L, consistent with guidelines in "How_to_annotate_molecular_adaptors" and "Molecular_adaptor_activity".

  3. The relationship "directly positively regulates" between the adaptor and the downstream activity (CUL1) is appropriate per the guidelines.

  4. Causal Relationships:

  5. The causal associations in the model use appropriate predicates:

    • RO:0002629 (directly positively regulates) for OPG025→CUL1
    • RO:0002630 (directly negatively regulates) for CUL1→IFITs
    • RO:0002304 (causally upstream of, positive effect) for IFNB1→IFITs

  6. Evidence Support:

  7. Most activities and causal relationships are well-supported with appropriate evidence codes and PMIDs.
  8. The evidence for most assertions comes from PMID:31644906 and PMID:11961546, which are relevant to this biological process.

Biological Accuracy

  1. Viral Strategy:
  2. The model accurately represents how poxviruses counteract host antiviral responses by targeting interferon-induced proteins (IFITs) for degradation.

  3. This is consistent with the UniProt entry for OPG025 (P17372), which states it "plays a role in the inhibition of host immune response by counteracting the action of interferons on early events in the viral replication cycle."

  4. Mechanism Accuracy:

  5. The model correctly shows that OPG025 contains ankyrin repeats and an F-box domain, making it capable of recruiting cellular ubiquitin ligase components (via CUL1).

  6. The role of CUL1 in the SCF ubiquitin ligase complex is properly represented.

  7. IFIT Function:

  8. The model accurately represents IFIT proteins as RNA-binding proteins involved in antiviral immune responses.

Areas for Improvement

  1. Missing Has Input Relationship:

  2. According to the molecular adaptor guidelines, the adaptor activity should have "has input" relationships to the molecules it brings together. In this case, the model is missing "has input" relationships from OPG025 to CUL1 and potentially to the IFIT proteins.

  3. Missing Specificity for SCF Complex Components:

  4. The model could benefit from including other components of the SCF complex (e.g., SKP1) which, according to the UniProt entry, also interact with OPG025.

  5. Ubiquitination Process Representation:

  6. The model implies degradation of IFIT proteins but doesn't explicitly show the ubiquitination process. This could be more clearly represented.

  7. Evidence for One Causal Association:

  8. One causal association from CUL1 to IFIT activities (first instance) has no evidence code or reference.

Conclusion

The GO-CAM model gomodel:62b4ffe300000717 is generally well-constructed and follows GO-CAM best practices. It accurately represents the biological mechanism by which Vaccinia virus protein OPG025/C9L counteracts the host interferon response by targeting IFIT proteins for proteasomal degradation.

The model is supported by appropriate literature evidence and represents a biologically meaningful pathway with correct causal relationships between activities. The one minor issue is the missing "has input" relationship for the molecular adaptor activity.

This model provides a clear representation of a viral evasion strategy targeting host innate immunity and could serve as a useful reference for similar host-pathogen interaction models.