Skip to content

Based on the model and additional information I've gathered, I'll now perform a comprehensive review of GO-CAM model 62b4ffe300002896.

Review of GO-CAM model 62b4ffe300002896

Overview of the Model

This model represents "Poxvirus-OPG043 inhibition of host PKR (Human-Poxvirus)" and illustrates the interaction between a poxvirus protein (P18378/OPG043/K3L) and the human protein kinase R (PKR) pathway. The model specifically shows how the poxvirus protein inhibits the host's antiviral response by interfering with the PKR-mediated translational regulation pathway.

Biological Content Assessment

The model is focused on a well-documented viral evasion mechanism where poxviruses encode proteins that act as pseudosubstrates to inhibit the host PKR kinase, preventing the shutdown of protein synthesis during viral infection.

The key components of the model are:

  1. Human PKR (P19525) - a key antiviral protein that phosphorylates eIF2α to block translation during viral infection
  2. Poxvirus protein K3L (P18378) - viral protein that inhibits PKR
  3. Human eIF2α (Q9BY44) - translation initiation factor targeted by PKR
  4. Human eIF2S2 (P20042) - beta subunit of eIF2 involved in translation initiation

The causal relationships modeled are: - Poxvirus K3L protein (P18378) has protein sequestering activity (GO:0140311) that directly negatively regulates (RO:0002630) the protein kinase activity (GO:0004672) of host PKR - PKR's protein kinase activity (GO:0004672) directly negatively regulates (RO:0002630) the translation initiation factor activity (GO:0003743) of eIF2α - eIF2α's translation initiation factor activity (GO:0003743) directly positively regulates (RO:0002629) the translation initiation factor activity (GO:0003743) of eIF2S2

Model Assessment

Strengths

  1. The core biological mechanism of viral inhibition of host PKR is accurately represented
  2. The model uses appropriate GO terms for functions (protein sequestering activity, kinase activity, translation initiation factor activity)
  3. The causal relationships use correct predicates (directly negatively/positively regulates)
  4. The model includes appropriate evidence codes and literature references
  5. All components are shown in the correct cellular location (cytoplasm)

Issues Identified

  1. PMID Reference Error: The model includes reference "PMID:248628414" which appears to be an incorrect format for a PubMed ID (usually PubMed IDs don't exceed 9 digits). This should be verified and corrected.

  2. Process Annotation: The model correctly annotates the processes (viral-host interaction, translational initiation, and antiviral response), but some processes could be more specifically annotated.

  3. Causal Flow Consistency: The model shows a pathway where poxvirus K3L inhibits PKR, which inhibits eIF2α. The model correctly shows PKR negatively regulating eIF2α, but I would suggest clarifying that this is specifically through phosphorylation.

  4. Complete Mechanism Representation: While the core mechanism is captured, the model could be enhanced by including:

  5. The role of viral dsRNA in activating PKR
  6. The specific phosphorylation of eIF2α at Ser-51
  7. More detail on how phosphorylated eIF2α blocks translation

Recommendations

  1. Fix Reference Error: Verify and correct the PMID:248628414 reference to ensure it points to the correct literature.

  2. Enhanced Activity Annotations: Consider adding more specific annotations:

  3. For PKR, specify that it phosphorylates eIF2α at Ser-51

  4. For eIF2α, clarify that when phosphorylated it sequesters eIF2B, preventing exchange of GDP for GTP

  5. Complete Causal Chain: Consider extending the model to include:

  6. The immediate upstream activator of PKR (viral dsRNA)
  7. The downstream effect of eIF2α phosphorylation (global translation inhibition)

  8. The specific outcome of translation inhibition (antiviral state)

  9. Additional Evidence: The model would be strengthened by including more recent literature that further validates this mechanism, especially papers that specifically address the K3L protein's role in immune evasion.

Conclusion

The GO-CAM model 62b4ffe300002896 provides an accurate representation of poxvirus inhibition of host PKR and the associated translational regulation pathway. The model accurately captures the core biological mechanism with appropriate GO terms, predicates, and evidence. With a few minor improvements to the reference and some additional mechanistic details, the model would provide an even more comprehensive representation of this important host-pathogen interaction.

Overall, this is a well-constructed model that effectively represents an important viral immune evasion mechanism at the molecular level.