Figure 4.

γ-34.5 deletion enhances safety and tumor-specificity of OHSV-IL12. (A) Healthy cells have inherent anti-viral defense mechanisms, such as protein kinase R (PKR). PKR phosphorylates translation initiation factor eIF2α, which shuts down synthesis of foreign proteins or viral antigens. (B) OHSV with an intact γ-34.5 overturns anti-viral defense in healthy cells through γ-34.5-mediated dephosphorylation of eIF2α and helps in viral protein synthesis/viral replication in healthy cells, leading to development of disease. (C) γ-34.5 deletion results in no eIF2α dephosphorylation in normal or healthy cells, and thereby, no protein synthesis and viral replication. (D) Cancer cells usually have defective PKR-eIF2α pathway, thus no inhibition of foreign protein synthesis. Therefore, γ-34.5-deleted OHSV can freely replicate in cancer cells.