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62b4ffe300003382 Poxvirus OPG038 inhibition of host CD80 CD86 Human Poxvirus

Now, let me review the GO-CAM model based on all the information gathered:

GO-CAM Model Review: gomodel:62b4ffe300003382

Model Overview

  • Title: "Poxvirus-OPG038 inhibition of host CD80/CD86 (Human-Poxvirus)"
  • Taxon: Human (NCBITaxon:9606)
  • Status: Production

Main Biological Process

This model represents how the vaccinia virus protein OPG038/M2 (UniProtKB:Q80HY2) inhibits T-cell mediated immunity by interfering with the CD80/CD86-CD28 costimulatory pathway. Specifically, the model shows:

  1. The vaccinia virus M2 protein (OPG038) has protein sequestering activity (GO:0140311)
  2. M2 protein directly negatively regulates (RO:0002630) the receptor ligand activity of both CD80 and CD86
  3. By preventing CD80 and CD86 from binding to CD28, the virus inhibits T-cell activation

Scientific Accuracy

The model accurately represents the findings from the literature, particularly from PMID:30918073, which demonstrated that:

  1. M2/OPG038 is secreted by vaccinia virus and forms a homo-oligomer
  2. This protein binds to both CD80 and CD86, blocking their interactions with CD28 and CTLA4
  3. This blocking activity impairs T-cell activation (GO:0042110)
  4. The mechanism contributes to negative regulation of T-cell mediated immunity (GO:0002710)

Model Components

The model includes the following key proteins and their activities:

  1. CD80 (P33681):
  2. Molecular function: Receptor ligand activity (GO:0048018)
  3. Cellular component: Plasma membrane (GO:0005886)

  4. Part of: Negative regulation of T cell mediated immunity (GO:0002710) and T cell activation (GO:0042110)

  5. CD86 (P42081):

  6. Molecular function: Receptor ligand activity (GO:0048018)
  7. Cellular component: Plasma membrane (GO:0005886)

  8. Part of: T cell activation (GO:0042110)

  9. Vaccinia virus OPG038/M2 (Q80HY2):

  10. Molecular function: Protein sequestering activity (GO:0140311)
  11. Cellular component: Extracellular space (GO:0005615)
  12. Part of: Symbiont-mediated suppression of host T-cell mediated immune response (GO:0052085)

  13. Causally regulates (negatively): CD80 and CD86 receptor ligand activities

  14. CD28 (P10747):

  15. Molecular function: Coreceptor activity (GO:0015026)
  16. Cellular component: Plasma membrane (GO:0005886)
  17. Part of: T cell activation (GO:0042110)

Causal Relationships

The causal relationships in the model correctly represent the biology:

  1. CD80 and CD86 directly positively regulate (RO:0002629) CD28 coreceptor activity
  2. OPG038/M2 directly negatively regulates (RO:0002630) CD80 and CD86 receptor ligand activity
  3. This negative regulation prevents CD80/CD86 from activating CD28, thereby inhibiting T-cell activation

Model Strengths

  1. The model accurately represents the mechanism by which vaccinia virus inhibits T-cell activation
  2. The causal relationships between proteins are correctly annotated
  3. The model includes appropriate evidence codes and PMID references
  4. The model clearly shows the suppression of host immunity by the viral protein

Suggestions for Improvement

  1. Add CD80-PD-L1 Interaction: The PMID:30918073 paper indicates that M2 actually potentiates CD80 binding to PD-L1, which could be added to provide a more complete picture of M2's activity.

  2. Add CTLA4 Interaction: The model focuses on CD28 but could also include CTLA4, as M2 also blocks CD80/CD86 binding to CTLA4 according to the paper.

  3. Annotation of M2 Oligomerization: The paper demonstrates that M2 forms a homo-oligomer (approximately 200 kDa), which is important for its function. This could be noted in the model.

Conclusion

Overall, the GO-CAM model "gomodel:62b4ffe300003382" is scientifically accurate and well-structured. It correctly represents the biological mechanism by which vaccinia virus protein OPG038/M2 interferes with T-cell activation by sequestering CD80 and CD86 proteins, thereby preventing their interaction with CD28. The model is consistent with the literature and captures the essential aspects of this viral immune evasion strategy.

The model is parsimonious and should be easily understandable to most biologists, as it clearly shows the pathway from viral protein activity to inhibition of host immune function.