Spontaneous and Engineered Compensatory HSV Mutants that Counteract the Host Antiviral PKR Response

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 inter...

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Bibliographic Details
Published in:Viruses 2009-12, Vol.1 (3), p.510-522
Main Authors: Shah, Amish C, Parker, Jacqueline N, Shimamura, Masako, Cassady, Kevin A
Format: Article
Language:English
Subjects:
oncolytic HSV
PKR
Review
Δγ134.5
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Summary: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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v1030510