title: Inhibition of avian leukosis virus replication by vector-based RNA interference.
abstract: RNA interference (RNAi) has recently emerged as a promising antiviral technique in vertebrates. Although most studies have used exogenous short interfering RNAs (siRNAs) to inhibit viral replication, vectors expressing short hairpin RNAs (shRNA-mirs) in the context of a modified endogenous micro-RNA (miRNA) are more efficient and are practical for in vivo delivery. In this study, replication competent retroviral vectors were designed to deliver shRNA-mirs targeting subgroup B avian leukosis virus (ALV), the most effective of which reduced expression of protein targets by as much as 90% in cultured avian cells. Cells expressing shRNA-mirs targeting the tvb receptor sequence or the viral env(B) sequence significantly inhibited ALV(B) replication. This study demonstrates efficient antiviral RNAi in avian cells using shRNA-mirs expressed from pol II promoters, including an inducible promoter, allowing for the regulation of the antiviral effect by doxycycline.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. chenmo@msu.edu
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Granger
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Vanbrocklin
authors.forename: William S
authors.initials: WS
authors.lastname: Payne
authors.forename: Henry
authors.initials: H
authors.lastname: Hunt
authors.forename: Huanmin
authors.initials: H
authors.lastname: Zhang
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Dodgson
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Holmen
mesh_terms: D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D002460:Cell Line; D002645:Chickens; D003370:Coturnix; D005822:Genetic Vectors; D034622:RNA Interference; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014779:Virus Replication / Q000235:genetics*