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

被引：6

作者：

Shah, Amish C. ^{[2
]}

Parker, Jacqueline N. ^{[1
]}

Shimamura, Masako ^{[1
]}

Cassady, Kevin A. ^{[1
]}

机构：

[1] Univ Alabama Birmingham, Dept Pediat, Div Infect Dis, Birmingham, AL 35222 USA

[2] Univ Penn, Dept Pediat, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

来源：

VIRUSES-BASEL | 2009年 / 1卷 / 03期

关键词：

PKR; oncolytic HSV; Delta gamma(1)34.5; HERPES-SIMPLEX-VIRUS; HUMAN CYTOMEGALOVIRUS TRS1; PROTEIN-KINASE PKR; GAMMA(1)34.5 PROTEIN; PREMATURE SHUTOFF; 2ND-SITE MUTATION; INTERFERON ACTION; VECTOR G47-DELTA; TYPE-1; GENE;

D O I：

10.3390/v1030510

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A virulent recombinant HSV lacking the diploid gamma(1)34.5 gene (Delta gamma(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 Delta gamma(1)34.5 viruses. This review describes the development of new Delta gamma(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.

引用

页码：510 / 522

页数：13

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