title: Inhibition of simian immunodeficiency virus by foamy virus vectors expressing siRNAs.
abstract: 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.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Jeonghae
authors.initials: J
authors.lastname: Park
authors.forename: Peter
authors.initials: P
authors.lastname: Nadeau
authors.forename: James R
authors.initials: JR
authors.lastname: Zucali
authors.forename: Calvin M
authors.initials: CM
authors.lastname: Johnson
authors.forename: Ayalew
authors.initials: A
authors.lastname: Mergia
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015870:Gene Expression; D015752:Genes, env; D015757:Genes, rev; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D016092:Spumavirus / Q000235:genetics*; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering