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Updated: May 28, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Spontaneous and Engineered Compensatory HSV Mutants that Counteract the Host Antiviral PKR Response
Amish C Shah1, Jacqueline N Parker, Masako Shimamura
1University of Pennsylvania, Department of Pediatrics, Children's Hospital of Philadelphia, 34 Street and Civic Center Boulevard, Philadelphia, PA 19104-4399, USA; E-Mail: amishamish@gmail.com (A.C.S.).
Abstract:
A virulent recombinant HSV lacking the diploid γ(1)34.5 gene (Δγ(1)34.5) have been investigated over the last two decades both for anti-tumor therapy and as vaccine vectors. The first generation vectors, while safe, are incapable of sustained replication in the majority of treated patients. An interferon inducible host antiviral kinase, protein kinase R (PKR), limits late viral protein synthesis and replication of Δγ(1)34.5 viruses. This review describes the development of new Δγ(1)34.5 vectors, through serial passage selection and direct viral genome engineering, which demonstrate selective PKR evasion in targeted cells and improved viral replication without restoring neurovirulence.
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