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Viruses 2009, 1(3), 510-522; doi:10.3390/v1030510

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

1 University of Pennsylvania, Department of Pediatrics, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104-4399, USA 2 University of Alabama at Birmingham, Department of Pediatrics, Division of Infectious Disease, 1600 6th Avenue South, CHB 118C, Birmingham, AL 35222, USA
* Author to whom correspondence should be addressed.
Received: 24 August 2009 / Revised: 22 October 2009 / Accepted: 22 October 2009 / Published: 22 October 2009
(This article belongs to the Special Issue Antiviral Responses to Herpes Viruses)
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A virulent recombinant HSV lacking the diploid γ134.5 gene (Δγ134.5) 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 Δγ134.5 viruses. This review describes the development of new Δγ134.5 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.
Keywords: PKR; oncolytic HSV; Δγ134.5 PKR; oncolytic HSV; Δγ134.5
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Shah, A.C.; Parker, J.N.; Shimamura, M.; Cassady, K.A. Spontaneous and Engineered Compensatory HSV Mutants that Counteract the Host Antiviral PKR Response. Viruses 2009, 1, 510-522.

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