Zhang_2009_Mol.Genet.Genomics_282_417

Reference

Title : The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation - Zhang_2009_Mol.Genet.Genomics_282_417
Author(s) : Zhang Q , Liang C , Yu YA , Chen N , Dandekar T , Szalay AA
Ref : Mol Genet Genomics , 282 :417 , 2009
Abstract :

As a new anticancer treatment option, vaccinia virus (VACV) has shown remarkable antitumor activities (oncolysis) in preclinical studies, but potential infection of other organs remains a safety concern. We present here genome comparisons between the de novo sequence of GLV-1h68, a recombinant VACV, and other VACVs. The identified differences in open reading frames (ORFs) include genes encoding host-range selection, virulence and immune modulation proteins, e.g., ankyrin-like proteins, serine proteinase inhibitor SPI-2/CrmA, tumor necrosis factor (TNF) receptor homolog CrmC, semaphorin-like and interleukin-1 receptor homolog proteins. Phylogenetic analyses indicate that GLV-1h68 is closest to Lister strains but has lost several ORFs present in its parental LIVP strain, including genes encoding CrmE and a viral Golgi anti-apoptotic protein, v-GAAP. The reduced pathogenicity of GLV-1h68 is confirmed in male mice bearing C6 rat glioma and in immunocompetent mice bearing B16-F10 murine melanoma. The contribution of foreign gene expression cassettes in the F14.5L, J2R and A56R loci is analyzed, in particular the contribution of F14.5L inactivation to the reduced virulence is demonstrated by comparing the virulence of GLV-1h68 with its F14.5L-null and revertant viruses. GLV-1h68 is a promising engineered VACV variant for anticancer therapy with tumor-specific replication, reduced pathogenicity and benign tissue tropism.

PubMedSearch : Zhang_2009_Mol.Genet.Genomics_282_417
PubMedID: 19701652
Gene_locus related to this paper: cowvi-M5L

Related information

Gene_locus cowvi-M5L

Citations formats

Zhang Q, Liang C, Yu YA, Chen N, Dandekar T, Szalay AA (2009)
The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation
Mol Genet Genomics 282 :417

Zhang Q, Liang C, Yu YA, Chen N, Dandekar T, Szalay AA (2009)
Mol Genet Genomics 282 :417