Inhibition of simian immunodeficiency virus by foamy virus vectors expressing siRNAs
- Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610 (United States)
- Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610 (United States)
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849-5519 (United States)
Viral vectors available for gene therapy are either inefficient or suffer from safety concerns for human applications. Foamy viruses are non-pathogenic retroviruses that offer several unique opportunities for gene transfer in various cell types from different species. In this report, we describe the use of simian foamy virus type 1 (SFV-1) vector to examine the efficacy of therapeutic genes. Hairpin short-interfering RNA (siRNA) that targets the simian immunodeficiency virus (SIV) rev/env was placed under the control of the PolIII U6 snRNA promoter for expression and screened for silencing target genes using cognate target-reporter fusions. We have identified an effective siRNA (designated R2) which reduces the rev and env gene expression by 89% and 95%, respectively. Using the simian foamy virus type 1 (SFV-1) based vector, we delivered the PolIII expressed R2 siRNA into cultured cells and challenged with SIV. The results show that the R2 siRNA is a potent inhibitor of SIV replication as determined by p27 expression and reverse transcriptase assays. Vectors based on a non-pathogenic SFV-1 vector may provide a safe and efficient alternative to currently available vectors, and the SIV model will help devise protocols for effective anti-HIV gene therapy.
- OSTI ID:
- 20779444
- Journal Information:
- Virology, Journal Name: Virology Journal Issue: 2 Vol. 343; ISSN VIRLAX; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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