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

Matthew McCown, Michael S. Diamond, Andrew Pekosz

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

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 M2 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.

Original languageEnglish
Pages (from-to)514-524
Number of pages11
JournalVirology
Volume313
Issue number2
DOIs
StatePublished - Sep 1 2003

Keywords

  • Antivirals
  • Gene expression
  • Influenza A virus
  • RNA interference
  • West Nile virus

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