Reduction in severity of a herpes simplex virus type 1 murine infection by treatment with a ribozyme targeting the UL20 gene RNA.

Abstract

Hammerhead ribozymes were designed to target mRNA of several essential herpes simplex virus type 1 (HSV-1) genes. A ribozyme specific for the late gene U(L)20 was packaged in an adenovirus vector (Ad-U(L)20 Rz) and evaluated for its capacity to inhibit the viral replication of several HSV-1 strains, including that of the wild-type HSV-1 (17syn+ and KOS) and several acycloguanosine-resistant strains (PAAr5, tkLTRZ1, and ACGr4) in tissue culture. The Ad-U(L)20 Rz was also tested for its ability to block an HSV-1 infection, using the mouse footpad model. Mouse footpads were treated with either the Ad-U(L)20 Rz or an adenoviral vector expressing green fluorescent protein (Ad-GFP) and then infected immediately thereafter with 10(4) PFU of HSV-1 strain 17syn+. Ad-U(L)20 ribozyme treatment consistently led to a 90% rate of protection for mice from lethal HSV-1 infection, while the survival rate in the control groups was less than 45%. Consistent with this protective effect, treatment with the Ad-U(L)20 Rz reduced the viral DNA load in the feet, the dorsal root ganglia, and the spinal cord relative to that of the Ad-GFP-treated animals. This study suggests that ribozymes targeting essential genes of the late kinetic class may represent a new therapeutic strategy for inhibiting HSV infection.

• Authors: Jia Liu, Alfred S Lewin, Sonal S Tuli, Steven C Ghivizzani, Gregory S Schultz, David C Bloom
• Journal: Journal of virology (J Virol) Vol. 82 Issue 15 Pg. 7467-74 (Aug 2008) ISSN: 1098-5514 [Electronic] United States
• PMID: 18508896 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• DNA, Viral
• RNA, Catalytic
• UL20 protein, Herpes simplex virus type 1
• Viral Proteins
• hammerhead ribozyme

Topics

• Adenoviridae (genetics)
• Animals
• Antiviral Agents (metabolism, therapeutic use)
• DNA, Viral (genetics)
• Foot (virology)
• Ganglia, Spinal (virology)
• Genetic Therapy (methods)
• Genetic Vectors
• Herpes Simplex
• Herpesvirus 1, Human (drug effects, genetics)
• Kinetics
• Mice
• RNA, Catalytic (genetics, metabolism, therapeutic use)
• Spinal Cord (virology)
• Survival Analysis
• Transduction, Genetic
• Viral Proteins (antagonists & inhibitors, genetics)