Inhibition of avian leukosis virus replication by vector-based RNA interference.
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.
Chen
Mo
M
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. chenmo@msu.edu
Granger
Adam J
AJ
Vanbrocklin
Matthew W
MW
Payne
William S
WS
Hunt
Henry
H
Zhang
Huanmin
H
Dodgson
Jerry B
JB
Holmen
Sheri L
SL
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*