Regulation of herpes simplex virus gamma(1)34.5 expression and oncolysis of diffuse liver metastases by Myb34.5

The Journal of Clinical Investigation
Hideo NakamuraKenneth K Tanabe

Abstract

Myb34.5 is a herpes simplex virus 1 (HSV-1) mutant deleted in the gene for ribonucleotide reductase (ICP6). It also carries a version of gamma(1)34.5 (a viral gene product that promotes the dephosphorylation of eIF-2alpha) that is under control of the E2F-responsive cellular B-myb promoter, rather than of its endogenous promoter. Myb34.5 replication in tumor cells results in their destruction (oncolysis). gamma(1)34.5 expression by HSV-1 subverts an important cell defense mechanism against viral replication by preventing shutoff of protein synthesis after viral infection. Infection of colon carcinoma cells with Myb34.5 results in greater eIF-2alpha dephosphorylation and viral replication compared with infection with HSV-1 mutants completely defective in gamma(1)34.5 expression. In contrast, infection of normal hepatocytes with Myb34.5 results in low levels of eIF-2alpha dephosphorylation and viral replication that are similar to those observed with HSV-1 mutants completely defective in gamma(1)34.5 and ICP6. When administered intravascularly into mice with diffuse liver metastases, Myb34.5 has greater antineoplastic activity than HSV-1 mutants with completely defective gamma(1)34.5 expression and more restricted biodistribution...Continue Reading

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Citations

Apr 5, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mark A CurrierTimothy P Cripe
Nov 3, 2006·Journal of Virology·Stephanie A CampbellMatthias Gromeier
Nov 20, 2012·Molekuliarnaia biologiia·P M ChumakovN V Tikunova

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Methods Mentioned

BETA
protein assay
electrophoresis
PCR
genetic modifications

Software Mentioned

InStat
ImageQuant

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