The utility of siRNA transcripts produced by RNA polymerase i in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses.
Short interfering double-stranded RNAs (siRNAs) expressed under the control of an RNA polymerase I promoter system were used to target gene expression of influenza A and West Nile virus. Decreased RNA and protein expression was induced in a sequence-specific manner-reducing sequence complementarity from 21 to 17 nucleotides abrogated the siRNA effect. Reduced M(2) expression resulted in a decrease in total and infectious influenza A virus production. WNV protein expression, genomic RNA, and infectious virus production were all dramatically reduced by siRNAs targeting two distinct viral sequences. The data demonstrate the utility of plasmid-driven siRNAs in regulating the expression of single viral genes, global viral gene expression, as a potential antiviral treatment, and as a genetic tool for viruses whose genomes are difficult to manipulate.
McCown
Matthew
M
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Diamond
Michael S
MS
Pekosz
Andrew
A
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D051379:Mice; D034622:RNA Interference; D012318:RNA Polymerase I / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D014158:Transcription, Genetic; D014170:Transformation, Genetic; D014763:Viral Matrix Proteins / Q000378:metabolism; D014779:Virus Replication; D014902:West Nile virus / Q000235:genetics / Q000502:physiology*
C031540:M-protein, influenza virus; D034741:RNA, Small Interfering; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D012318:RNA Polymerase I