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Journal of Virology, August 2008, p. 7467-7474, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02720-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Reduction in Severity of a Herpes Simplex Virus Type 1 Murine Infection by Treatment with a Ribozyme Targeting the UL20 Gene RNA{triangledown}

Jia Liu,1 Alfred S. Lewin,1 Sonal S. Tuli,2 Steven C. Ghivizzani,3 Gregory S. Schultz,4 and David C. Bloom1*

Departments of Molecular Genetics and Microbiology,1 Ophthalmology,2 Orthopedics,3 Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida 32610-02664

Received 21 December 2007/ Accepted 16 May 2008

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 UL20 was packaged in an adenovirus vector (Ad-UL20 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-UL20 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-UL20 Rz or an adenoviral vector expressing green fluorescent protein (Ad-GFP) and then infected immediately thereafter with 104 PFU of HSV-1 strain 17syn+. Ad-UL20 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-UL20 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.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, Box 100266, University of Florida College of Medicine, Gainesville, FL 32610-0266. Phone: (352) 392-8520. Fax: (352) 392-3133. E-mail: dbloom{at}ufl.edu

{triangledown} Published ahead of print on 28 May 2008.

Journal of Virology, August 2008, p. 7467-7474, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02720-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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