scholarly journals Comparative in vitro and in vivo cytotoxic activity of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) and its arabinosyl derivative, (E)-5-(2-bromovinyl)-1-β-D-arabinofuranosyluracil (BVaraU), against tumor cells expressing either the Varicella zoster or the Herpes simplex virus thymidine kinase

2000 ◽  
Vol 7 (2) ◽  
pp. 215-223 ◽  
Author(s):  
Christine Grignet-Debrus ◽  
Vincent Cool ◽  
Nathalie Baudson ◽  
Bart Degrève ◽  
Jan Balzarini ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cytotoxic Activity ◽  
Thymidine Kinase ◽  
Tumor Cells ◽  
Varicella Zoster ◽  
Simplex Virus

scholarly journals Identification of a complex associated with processing and polyadenylation in vitro of herpes simplex virus type 1 thymidine kinase precursor RNA.

1987 ◽  
Vol 7 (9) ◽  
pp. 3277-3286 ◽  
Author(s):  
F Zhang ◽  
C N Cole
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Herpes Simplex Virus Type ◽  
Rna Processing ◽  
Polyadenylation Signal ◽  
Simplex Virus

Cleavage and polyadenylation of substrate RNAs containing the herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) gene polyadenylation signal region were examined in HeLa cell nuclear extract. 3'-End RNA processing was accurate and efficient and required ATP and Mg2+. Cleavage, but not polyadenylation, occurred in the presence of EDTA or when ATP was replaced with 3' dATP (cordycepin) or AMP(CH2)PP, a nonhydrolyzable analog of ATP. Processing in vitro and in vivo showed the same signal element requirements: a series of substrates containing linker scanning, internal deletion, and small insertion mutations was processed with the same relative efficiencies and at the same sites in vitro and in vivo. A complex involved in 3'-end RNA processing was identified by gel mobility shift analysis. This complex formed rapidly, reached a maximum level after 20 to 30 min, and was much reduced after 2 h. Very little complex was formed at 0 degree C or with substrates lacking a polyadenylation signal. Entry of 32P-labeled tk substrate into the complex could be prevented by addition of excess 35S-labeled tk or adenovirus L3 precursor RNAs. Competition was not observed with tk RNAs lacking a complete polyadenylation signal.

A Comparative Study of the in vitro and in vivo Antiviral Activities of Acyclovir and Penciclovir

1995 ◽  
Vol 6 (2) ◽  
pp. 89-97 ◽  
Author(s):  
P. Ertl ◽  
W. Snowden ◽  
D. Lowe ◽  
W. Miller ◽  
P. Collins ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Varicella Zoster ◽  
Significant Difference ◽  
Simplex Virus ◽  
Hsv 1

The antiviral properties of the compounds acyclovir (ACV) and penciclovir (PCV) have been compared in a number of in vitro and in vivo assays. In vitro, both compounds had good activity against herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV), although ACV showed statistically significant superiority. In addition, ACV had greater activity against herpes simplex virus type 2 (HSV-2), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). We examined the effect of time of addition and removal of ACV and PCV under a variety of conditions and found similar results with the two compounds under most conditions. However, at a high multiplicity of infection, when all of the cells would be expected to be synchronously expressing large amounts of the viral thymidine kinase, short exposures to PCV appeared to be superior to similar exposures to ACV. In the HSV-1 zosteriform mouse model there was no significant difference between the activities of ACV and PCV, or its prodrug famciclovir (FCV), in once- or twice-daily treatment. The possible significance of these results and those previously reported on the activity of the compounds in humans is discussed.

scholarly journals Activated MEK Suppresses Activation of PKR and Enables Efficient Replication and In Vivo Oncolysis by Δγ134.5 Mutants of Herpes Simplex Virus 1

2006 ◽  
Vol 80 (3) ◽  
pp. 1110-1120 ◽  
Author(s):  
Kerrington D. Smith ◽  
James J. Mezhir ◽  
Kai Bickenbach ◽  
Jula Veerapong ◽  
Jean Charron ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Dominant Negative ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus

ABSTRACT Herpes simplex virus mutants lacking the γ134.5 gene are not destructive to normal tissues but are potent cytolytic agents in human tumor cells in which the activation of double-stranded RNA-dependent protein kinase (PKR) is suppressed. Thus, replication of a Δγ134.5 mutant (R3616) in 12 genetically defined cancer cell lines correlates with suppression of PKR but not with the genotype of RAS. Extensive analyses of two cell lines transduced with either dominant negative MEK (dnMEK) or constitutively active MEK (caMEK) indicated that in R3616 mutant-infected cells dnMEK enabled PKR activation and decreased virus yields, whereas caMEK suppressed PKR and enabled better viral replication and cell destruction in transduced cells in vitro or in mouse xenografts. The results indicate that activated MEK mediates the suppression of PKR and that the status of MEK predicts the ability of Δγ134.5 mutant viruses to replicate in and destroy tumor cells.

Identification of a complex associated with processing and polyadenylation in vitro of herpes simplex virus type 1 thymidine kinase precursor RNA

1987 ◽  
Vol 7 (9) ◽  
pp. 3277-3286
Author(s):  
F Zhang ◽  
C N Cole
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Herpes Simplex Virus Type ◽  
Rna Processing ◽  
Polyadenylation Signal ◽  
Simplex Virus

Cleavage and polyadenylation of substrate RNAs containing the herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) gene polyadenylation signal region were examined in HeLa cell nuclear extract. 3'-End RNA processing was accurate and efficient and required ATP and Mg2+. Cleavage, but not polyadenylation, occurred in the presence of EDTA or when ATP was replaced with 3' dATP (cordycepin) or AMP(CH2)PP, a nonhydrolyzable analog of ATP. Processing in vitro and in vivo showed the same signal element requirements: a series of substrates containing linker scanning, internal deletion, and small insertion mutations was processed with the same relative efficiencies and at the same sites in vitro and in vivo. A complex involved in 3'-end RNA processing was identified by gel mobility shift analysis. This complex formed rapidly, reached a maximum level after 20 to 30 min, and was much reduced after 2 h. Very little complex was formed at 0 degree C or with substrates lacking a polyadenylation signal. Entry of 32P-labeled tk substrate into the complex could be prevented by addition of excess 35S-labeled tk or adenovirus L3 precursor RNAs. Competition was not observed with tk RNAs lacking a complete polyadenylation signal.

scholarly journals Retinoids augment the bystander effect in vitro and in vivo in herpes simplex virus thymidine kinase/ganciclovir-mediated gene therapy

Gene Therapy ◽  
1997 ◽  
Vol 4 (9) ◽  
pp. 909-917 ◽  
Author(s):  
JY Park ◽  
AA Elshami ◽  
K Amin ◽  
N Rizk ◽  
LR Kaiser ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Bystander Effect ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus Type 1 Entry Is Inhibited by the Cobalt Chelate Complex CTC-96

2001 ◽  
Vol 75 (9) ◽  
pp. 4117-4128 ◽  
Author(s):  
Jennifer A. Schwartz ◽  
Erik K. Lium ◽  
Saul J. Silverstein
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Syncytium Formation ◽  
Fusion Event ◽  
Varicella Zoster ◽  
Cell Monolayers ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The CTC series of cobalt chelates display in vitro and in vivo activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). The experiments described here identify the stage in the virus life cycle where CTC-96 acts and demonstrate that the drug inhibits infection of susceptible cells. CTC-96 at 50 μg/ml has no effect on adsorption of virions to Vero cell monolayers. Penetration assays reveal that CTC-96 inhibits entry of the virus independent of gC and cellular entry receptors. This observation was supported by the failure to detect the accumulation of virus-specified proteins and α mRNA transcripts when CTC-96 is present at the onset of infection. Moreover, virion-associated αTIF does not accumulate in the nucleus of cells infected in the presence of CTC-96. CTC-96 targets the initial fusion event between the virus and the cell and also inhibits cell-to-cell spread and syncytium formation. Furthermore, CTC-96 inhibits plaque formation by varicella-zoster virus and vesicular stomatitis virus as efficiently as by HSV-1. Collectively, these experiments suggest that CTC-96 is a broad-spectrum inhibitor of infection by enveloped viruses and that it inhibits HSV-1 infection at the point of membrane fusion independent of the type of virus and cellular receptors present.

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