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62b4ffe300005096 Poxvirus OPG022 inhibition of host IL18 signaling pathway Human Poxvirus

Now, let me review the model in detail based on the information gathered.

Based on the information gathered, I'll now review the GO-CAM model gomodel:62b4ffe300005096, which represents "Poxvirus-OPG022 inhibition of host IL18 signaling pathway (Human-Poxvirus)".

GO-CAM Model Review

Model Overview:

This model represents the interaction between a poxvirus protein (OPG022/VACWR013) and the human IL-18 signaling pathway. It shows how the viral protein inhibits IL-18 signaling as a viral immune evasion strategy. The model includes:

  1. Human IL-18 (Q14116) with cytokine activity (GO:0005125)
  2. Human IL-18 receptor alpha chain (IL18R1, Q13478) with interleukin-18 receptor activity (GO:0042008)
  3. Human IL-18 receptor accessory protein (IL18RAP, O95256) with coreceptor activity (GO:0015026)
  4. Poxvirus IL-18 binding protein (P17357) with receptor decoy activity (GO:0140319)

All activities are part of the interleukin-18-mediated signaling pathway (GO:0035655), with the viral protein being part of a viral process aimed at suppressing host immune response.

Detailed Assessment:

1. Structural Assessment:

The model follows the GO-CAM best practices for representing receptor-ligand interactions according to the "Signaling receptor activity annotation guidelines":

  • IL-18 is properly annotated with cytokine activity (GO:0005125), which is a type of receptor ligand activity
  • IL-18 is correctly shown to occur in the extracellular space (GO:0005615), which is appropriate for a secreted cytokine
  • IL-18R1 is properly annotated with interleukin-18 receptor activity (GO:0042008), a type of signaling receptor activity
  • IL-18R1 is correctly shown to occur in the plasma membrane (GO:0005886)
  • IL-18RAP is properly annotated with coreceptor activity (GO:0015026)
  • IL-18RAP is correctly shown to occur in the plasma membrane (GO:0005886)

2. Causal Relations:

The model uses appropriate causal relations:

  • IL-18 directly positively regulates (RO:0002629) IL-18R1 activity
  • IL-18R1 directly positively regulates (RO:0002629) IL-18RAP activity
  • The viral IL-18BP directly negatively regulates (RO:0002630) IL-18 activity

3. Biological Content Assessment:

The biological content of the model is consistent with the literature:

  • The model correctly represents the IL-18 signaling pathway, where IL-18 binds to IL-18R1, which then recruits IL-18RAP to form a functional receptor complex
  • The poxvirus IL-18BP acts as a decoy receptor to sequester IL-18, preventing it from binding to its cellular receptor
  • All the components are associated with the correct biological process (GO:0035655, interleukin-18-mediated signaling pathway)
  • The viral protein is correctly associated with the viral process GO:0039518 (obsolete suppression by virus of host cytokine activity)

4. Evidence Assessment:

The model uses appropriate evidence codes and references:

  • The evidence for IL-18 cytokine activity comes from a direct assay (ECO:0000314) with reference to PMID:14528293
  • The evidence for IL-18R1 and IL-18RAP activities and their cellular locations comes from direct assays or curator inference with references to appropriate papers (PMID:25500532)
  • The evidence for the viral IL-18BP activity comes from direct assay (ECO:0000314) with reference to PMID:10769064, which directly demonstrates that poxviruses encode IL-18 binding proteins that block IL-18 activity

Issues Found:

  1. Obsolete Term Usage: The model uses the term "obsolete suppression by virus of host cytokine activity" (GO:0039518) for the viral process. As this term is marked as obsolete, it should be updated to the current replacement term.

  2. Automated Changes: The model has undergone automated term replacements (noted in comments), indicating it was created before some relationship type standardizations. While these changes don't affect the model's validity, it's worth noting that the model was created using older relationship types.

  3. Cellular Location Precision: IL-18R1 and IL-18RAP are annotated to plasma membrane (GO:0005886), which is correct, but for transmembrane receptors, a more specific term like "integral component of plasma membrane" might be more precise if this information is available in the literature.

Conclusion:

Overall, this is a well-constructed GO-CAM model that accurately represents the inhibition of the IL-18 signaling pathway by a poxvirus IL-18 binding protein. The model follows GO-CAM best practices for signaling receptor annotation and uses appropriate evidence. The only notable issue is the use of an obsolete GO term for the viral process, which should be updated.

The model is parsimonious, focusing on the key interactions without unnecessary complexity, and it clearly communicates the biological mechanism of viral immune evasion through cytokine inhibition.

Recommendation: Update the obsolete GO term (GO:0039518), but otherwise, the model is sound and can be maintained as is.